October 2006
575 Pages
US$ 2,200 (electronic).

Summary
Nanotechnology is the creation and utilization of materials, devices, and systems through the control of matter on the nanometer-length scale (a nanometer is one billionth of a meter. Nanobiotechnology, an integration of physical sciences, molecular engineering, biology, chemistry and biotechnology holds considerable promise of advances in pharmaceuticals and healthcare. The report starts with an introduction to various techniques and materials that are relevant to nanobiotechnology. It includes some of the physical forms of energy such as nanolasers. Some of the technologies are scaling down such as microfluidics to nanofluidic biochips and others are constructions from bottom up. Application in life sciences research, particularly at the cell level sets the stage for role of nanobiotechnology in healthcare in subsequent chapters.

Some of the earliest applications are in molecular diagnostics. Nanoparticles, particularly quantum dots, are playing important roles. In vitro diagnostics, does not have any of the safety concerns associated with the fate of nanoparticles introduced into the human body. Numerous nanodevices and nanosystems for sequencing single molecules of DNA are feasible. Various nanodiagnostics that have been reviewed will improve the sensitivity and extend the present limits of molecular diagnostics.

An increasing use of nanobiotechnology by the pharmaceutical and biotechnology industries is anticipated. Nanotechnology will be applied at all stages of drug development - from formulations for optimal delivery to diagnostic applications in clinical trials. Many of the assays based on nanobiotechnology will enable high-throughput screening. Some of nanostructures such as fullerenes are themselves drug candidates as they allow precise grafting of active chemical groups in three-dimensional orientations. The most important pharmaceutical applications are in drug delivery. Apart from offering a solution to solubility problems, nanobiotechnology provides and intracellular delivery possibilities. Skin penetration is improved in transdermal drug delivery. A particularly effective application is as nonviral gene therapy vectors. Nanotechnology has the potential to provide controlled release devices with autonomous operation guided by the needs.

Nanomedicine is now within the realm of reality starting with nanodiagnostics and drug delivery facilitated by nanobiotechnology. Miniature devices such as nanorobots could carry out integrated diagnosis and therapy by refined and minimally invasive procedures, nanosurgery, as an alternative to crude surgery. Nanotechnology will markedly improve the implants and tissue engineering approaches as well.

There is some concern about the safety of nanoparticles introduced in the human body and released into the environment. Research is underway to address these issues. As yet there are no FDA directives to regulate nanobiotechnology but as products are ready to enter market, these are expected to be in place.

Future nanobiotechnology markets are calculated on the basis of the background markets in the areas of application and the share of this market by new technologies and state of development at any given year in the future. This is based on a comprehensive and thorough review of the current status of nanobiotechnology, research work in progress and anticipated progress. There is definite indication of large growth of the market but it will be uneven and cannot be plotted as a steady growth curve. Marketing estimates are given according to areas of application, technologies and geographical distribution. The largest expansion is expected between the years 2010 and 2015.

Profiles of 218 companies, out of over 500 involved in this area, are included in the last chapter along with their 125 collaborations.The report is supplemented with 31 Tables, 17 figures and 400 references to the literature.

T A B L E O F C O N T E N T S
0. Executive Summary ........................................................................... 15
1. Basics of Nanobiotechnology .............................................................. 17
Introduction..................................................................................................................17
Classification of nanobiotechnologies.............................................................................18
Top-down and bottom-up approaches ............................................................................. 19
Landmarks in the evolution of nanobiotechnology ..........................................................19
Relation of nanobiotechnology to healthcare ..................................................................20
2. Technologies ..................................................................................... 23
Introduction..................................................................................................................23
Micro- and nano-electromechanical systems...................................................................23
BioMEMS.................................................................................................................... 23
Microarrays and nanoarrays...........................................................................................24
Dip Pen Nanolithography for nanoarrays.......................................................................... 24
Protein nanoarrays ...................................................................................................... 25
Microfluidics and nanofluidics ........................................................................................26
Nanotechnology on a chip............................................................................................. 26
Microfluidic chips for nanoliter volumes............................................................................ 27
Nanogen's NanoChip.................................................................................................... 28
Use of nanotechnology in microfluidics ............................................................................ 29
Construction of nanofluidic channels........................................................................... 29
Nanoscale flow visualization...................................................................................... 29
Moving (levitation) of nanofluidic drops with physical forces........................................... 30
Nanofluidics on nanopatterned surfaces ...................................................................... 30
Nano-interface in a microfluidic chip........................................................................... 31
Visualization and manipulation on nanoscale..................................................................31
Atomic force microscopy............................................................................................... 31
Basic AFM operation................................................................................................ 31
Advantages of AFM ................................................................................................. 31
Force sensing Integrated Readout and Active Tip.......................................................... 32
Ultra-nanocrystalline diamond ....................................................................................... 32
Magnetic resonance force microscopy.............................................................................. 33
Scanning probe microscopy........................................................................................... 33
Near-field scanning optical microscopy ............................................................................ 33
Multiple single-molecule fluorescence microscopy.............................................................. 34
Nanoparticle characterization by HaloÔ LM10 technology.................................................... 34
Nanoscale scanning electron microscopy.......................................................................... 35
Use of SEM to reconstruct three-dimensional tissue nanostructure................................... 35
Visualizing atoms with scanning electron microscopy..................................................... 36
Photoactivated localization microscopy ....................................................................... 36
Optical Imaging with a Silver Superlens........................................................................... 37
Fluorescence Resonance Energy Transfer......................................................................... 37
Cantilevers................................................................................................................. 37
Principle................................................................................................................ 37
Applications ........................................................................................................... 38
Surface plasmon resonance........................................................................................... 38
Nanoparticles................................................................................................................39
Quantum dots ............................................................................................................. 39
Gold nanoparticles....................................................................................................... 41
Silica nanoparticles ...................................................................................................... 41
Lipoparticles ............................................................................................................... 41
Biomedical applications of self-assembly of nanoparticles ................................................... 42
Paramagnetic and superparamagnetic nanoparticles.......................................................... 43
Fluorescent nanoparticles.............................................................................................. 43
Production techniques for nanoparticles........................................................................... 43
Nanostructures .............................................................................................................44
Cubosomes ................................................................................................................ 45
Nanoshells ................................................................................................................. 45
Nanotubes.................................................................................................................. 46
Carbon nanotubes................................................................................................... 46
Carbon nanotubes and DNA...................................................................................... 46
Applications of nanotubes......................................................................................... 47
Polymer nanofibers ...................................................................................................... 48
Nanowires.................................................................................................................. 48
Fullerenes.................................................................................................................. 48
Dendrimers ................................................................................................................ 49
Properties.............................................................................................................. 50
Applications ........................................................................................................... 50
DNA octahedron .......................................................................................................... 51
Potential applications............................................................................................... 51
Nanostamping............................................................................................................. 51
Nanoneedles............................................................................................................... 51
Nanopores.................................................................................................................. 52
Nanoporous silica aerogel ............................................................................................. 53
Bacterial structures relevant to nanobiotechnology ............................................................ 54
Bacterial spores...................................................................................................... 54
Nanostructures based on bacterial cell surface layers.................................................... 54
Bacterial magnetic particles...................................................................................... 55
DNA-nanoparticle conjugates......................................................................................... 55
Protein-nanoparticle combination ................................................................................... 55
Networks of gold nanoparticles and bacteriophage............................................................. 56
Nanostructured silicon.................................................................................................. 56
Nanomaterials for biolabeling ........................................................................................56
Quantum dots as labels................................................................................................ 58
Silver nanoparticle labels.............................................................................................. 58
Silica nanoparticles for labeling antibodies ....................................................................... 58
SERS nanotags ........................................................................................................... 59
Organic nanoparticles as biolabels.................................................................................. 59
Molecular computational identification ............................................................................. 59
Companies providing services and products for nanobiotechnology.................................60
3. Applications in Life Sciences............................................................... 61
Introduction..................................................................................................................61
Nanotechnology and biology ..........................................................................................61
NanoSystems Biology................................................................................................... 61
Nanobiology and the cell............................................................................................... 62
Quantum dots for cell labeling................................................................................... 63
Nanostructures involved in endocytosis....................................................................... 63
Study of complex biological systems .......................................................................... 63
Molecular motors .................................................................................................... 64
Nanomotor made of nucleic acids .............................................................................. 65
Biosensing of cellular responses ................................................................................ 66
Control of T cell signaling activity .............................................................................. 67
Light-activated ion channel molecular machines ........................................................... 67
Application of AFM for biomolecular imaging..................................................................... 67
Future insights into biomolecular processes by AFM ...................................................... 68
3D single-molecular imaging by coherent X-ray diffraction imaging ...................................... 68
Multi-isotope imaging mass spectrometry ........................................................................ 69
Applications of biomolecular computing in life sciences....................................................... 69
Molecular electronics.................................................................................................... 70
Microbial nanomaterials ................................................................................................ 70
Use of bacteria to construct nanomachines.................................................................. 70
Bacteriophage nanoshells......................................................................................... 70
Natural nanocomposites ............................................................................................... 71
Nanotechnology in biological research............................................................................. 71
Nanoparticles for biological research .......................................................................... 71
Disguising quantum dots as proteins for cell entry ........................................................ 72
Molecular biology and nanotechnology............................................................................. 73
DNA nanotechnology ............................................................................................... 73
Reversibly binding of gold nanospheres to DNA strands................................................. 74
RNA nanotechnology ............................................................................................... 74
Genetically engineered proteins for nanobiotechnology.................................................. 75
Optical trapping and single-molecule fluorescence ............................................................. 75
Nanochemistry ..............................................................................................................75
Nanoscale pH Meter ..................................................................................................... 76
Application of nanolasers in life sciences........................................................................76
Study of mitochondria with nanolaser spectroscopy ........................................................... 77
Nanomanipulation.........................................................................................................77
Nanomanipulation by combination of AFM and other devices ............................................... 77
Surgery on living cells using AFM with nanoneedles........................................................... 78
Optoelectronic tweezers................................................................................................ 78
Single molecule manipulation ........................................................................................ 78
Nanotechnology in genomic research .............................................................................79
Separation of DNA fragments ........................................................................................ 79
Nanoliter-scale DNA sequencing................................................................................ 79
Single-molecule detection of DNA hybridization................................................................. 79
Role of nanobiotechnology in identifying single nucleotide polymorphisms ............................. 80
Role of nanotechnology in proteomics research..............................................................80
Study of proteins by atomic force microscopy................................................................... 80
Nanoproteomics.......................................................................................................... 81
Multi Photon Detection............................................................................................. 81
Nanoflow liquid chromatography................................................................................ 81
High-field asymmetric waveform ion mobility mass spectrometry .................................... 82
Protein nanocrystallography...................................................................................... 82
QD-protein bioconjugate nanoassembly ...................................................................... 82
Nanoproteomics for study of misfolded proteins ........................................................... 82
Dynamic reassembly of peptides................................................................................ 83
Use of nanotube electronic biosensor in proteomics ...................................................... 83
Nanometer photomasks from bacterial protein ............................................................. 83
Proteomics at single molecule level................................................................................. 84
Study of protein synthesis and single-molecule processes.............................................. 84
Protein expression in individual cells at the single molecule level..................................... 85
Biochips for nanoscale proteomics.................................................................................. 85
Protein biochips based on fluorescence planar wave guide technology .............................. 85
Nanofilter array chip................................................................................................ 86
Role of nanotechnology in study of membrane proteins ...................................................... 86
Nanoparticles for study of membrane proteins ............................................................. 86
Study of single protein interaction with cell membrane .................................................. 86
Quantum dots to label cell surface proteins ................................................................. 87
Study of single membrane proteins at subnanometer resolution...................................... 87
Protein engineering on nanoscale ................................................................................... 87
Nanowires for protein engineering ............................................................................. 87
A nanoscale mechanism for protein engineering........................................................... 88
Role of nanotechnology in peptide engineering............................................................. 88
Manipulating redox systems for nanotechnology................................................................ 88
Self-assembling peptide scaffold technology for 3-D cell culture........................................... 89
Nanobiotechnology and ion channels .............................................................................89
Aquaporin water channels ............................................................................................. 90
Role of nanobiotechnology in engineering ion channels....................................................... 90
Application of nanobiotechnology in molecular electronics..............................................91
Nanotechnology and bioinformatics ...............................................................................92
3D nano-map of synapse.............................................................................................. 92
Companies providing nanotechnology for life sciences research......................................93
4. Nanomolecular Diagnostics ................................................................ 95
Introduction..................................................................................................................95
Nanodiagnostics............................................................................................................95
Rationale of nanotechnology for molecular diagnostics....................................................... 96
Nanofluidic device to trap a single molecule of DNA ...................................................... 97
Nanoarrays for molecular diagnostics ............................................................................97
NanoPro™ System ....................................................................................................... 97
Nanoparticle protein chip.............................................................................................. 98
Protein nanobiochip ..................................................................................................... 98
Self-assembling protein nanoarrays................................................................................ 98
Nanoparticles for molecular diagnostics .........................................................................99
Gold nanoparticles....................................................................................................... 99
Quantum dots for molecular diagnostics .......................................................................... 99
Quantum dots for detection of pathogenic microorganisms........................................... 100
Imaging of living tissue with quantum dots................................................................ 100
Magnetic nanoparticles ............................................................................................... 101
Superparamagnetic nanoparticles for cell tracking ...................................................... 101
Superparamagnetic iron oxide nanoparticles for calcium sensing ................................... 102
Magnetic nanoparticles for labeling molecules ............................................................ 102
Ferrofluids........................................................................................................... 102
Super conducting quantum interference device .......................................................... 102
Study of living cells by superparamagnetic nanoparticles ............................................. 103
Use of nanocrystals in immunohistochemistry................................................................. 103
Imaging applications of nanoparticles............................................................................ 103
Superparamagnetic nanoparticles combined with MRI ................................................. 104
Nanoparticles as contrast agent for MRI.................................................................... 104
Gadonanotubes for MRI ......................................................................................... 105
Quantum dots for biological imaging ........................................................................ 105
Gold nanorods as imaging agents ............................................................................ 106
Nanoparticles vs microparticles for cellular imaging..................................................... 106
Intravital vascular imaging..................................................................................... 106
Study of chromosomes by atomic force microscopy ......................................................106
Applications of nanopore technology for molecular diagnostics.....................................107
DNA-protein and -nanoparticle conjugates ...................................................................107
Cantilever arrays for molecular diagnostics ..................................................................108
Advantages of cantilever technology for molecular recognition........................................... 109
Portable nanocantilever system for diagnosis.................................................................. 109
Resonance Light Scattering technology ........................................................................110
DNA nanomachines for molecular diagnostics...............................................................110
Nanobarcodes technology ............................................................................................111
Nanobarcodes with striping metallic patterns.................................................................. 111
Biobarcode assay for proteins ...................................................................................... 111
Nanobarcode particle technology for SNP genotyping ....................................................... 112
Qdot nanobarcode for multiplexed gene expression profiling ............................................. 113
Nanoparticle-based colorimetric DNA detection method................................................113
SNP genotyping with gold nanoparticle probes................................................................ 114
Nanoparticle-based Up-converting Phosphor Technology ..............................................114
Surface-Enhanced Resonant Raman Spectroscopy ........................................................114
Near-infrared (NIR)-emissive polymersomes ...............................................................115
Nanobiotechnology for detection of proteins ................................................................116
Captamers with proximity extension assay for proteins .................................................... 116
Nanobiosensors...........................................................................................................116
Carbon nanotube biosensors........................................................................................ 117
Carbon nanotube sensors coated with ssDNA and electronic readout.............................. 117
Carbon nanotubes sensors wrapped with DNA and optical detection............................... 117
QD-based DNA nanosensor ......................................................................................... 118
Ion Channel Switch biosensor technology....................................................................... 118
Electronic nanobiosensors ........................................................................................... 118
Electrochemical nanobiosensor..................................................................................... 119
Quartz nanobalance biosensor ..................................................................................... 119
Viral nanosensor ....................................................................................................... 119
PEBBLE nanosensors .................................................................................................. 119
Nanosensors for glucose monitoring.............................................................................. 120
Microneedle-mounted biosensor ................................................................................... 120
Optical biosensors ..................................................................................................... 121
Laser nanosensors................................................................................................ 121
Nanocantilever biosensors...................................................................................... 121
Nanoshell biosensors............................................................................................. 122
Plasmonics and SERS nanoprobes............................................................................ 122
Novel optical mRNA biosensor................................................................................. 122
Optonanogen biosensor ......................................................................................... 123
Surface plasmon resonance technology..................................................................... 124
Nanowire biosensors.................................................................................................. 124
Nanowire biosensors for detection of single viruses..................................................... 125
Nanowires for detection of genetic disorders.............................................................. 125
Nanowires biosensor for detecting biowarfare agents .................................................. 125
Nanoscale erasable biodetectors................................................................................... 125
Future issues in the development of nanobiosensors........................................................ 126
Applications of nanodiagnostics...................................................................................127
Nanotechnology for detection of biomarkers................................................................... 127
Protease-activated quantum dot probes......................................................................... 128
Nanotechnology for detection of cancer......................................................................... 128
QDs for cancer diagnosis........................................................................................ 128
Gold nanoparticles for cancer diagnosis .................................................................... 129
Nanoatomic tubes for detection of cancer proteins...................................................... 129
Nanoparticles for the optical imaging of tumors.......................................................... 130
Nanolaser spectroscopy for detection of cancer in single cells ....................................... 130
Nanotechnology for point-of-care diagnostics ................................................................. 130
Nanoprobes for POC diagnosis................................................................................. 130
Carbon nanotube transistors for genetic screening...................................................... 131
Detection of infectious agents...................................................................................... 131
SEnsing of Phage-Triggered Ion Cascade for detection of bacteria ................................. 132
Detection of single virus particles ............................................................................ 132
Fluorescent QD probes for detection of respiratory viral infections................................. 132
Nanodiagnostics for integrating diagnostics with therapeutics............................................ 134
Companies involved in nanomolecular diagnostics........................................................134
Concluding remarks and future prospects of nanodiagnostics .......................................137
5. Nanobiotechnology in Drug Discovery & Development....................... 139
Introduction................................................................................................................139
Nanobiotechnology for drug discovery .........................................................................139
Gold nanoparticles for drug discovery............................................................................ 140
Tracking drug molecules in cells.............................................................................. 140
SPR with colloidal gold particles............................................................................... 140
Use of quantum dots for drug discovery......................................................................... 141
Advantages of the use of QDs for drug discovery........................................................ 141
Drawbacks of the use of QDs for drug discovery......................................................... 141
Quantum dot for imaging drug receptors in the brain.................................................. 142
Ligand-conjugated nanocrystals................................................................................... 142
Lipoparticles for drug discovery.................................................................................... 142
Biosensor for drug discovery with Lipoparticles .......................................................... 142
Magnetic nanoparticles assays..................................................................................... 143
Micelles for drug discovery .......................................................................................... 143
Nanolasers for drug discovery...................................................................................... 143
Analysis of small molecule-protein interactions by nanowire biosensors............................... 144
Cells targeting by nanoparticles with attached small molecules .......................................... 144
Role of AFM for study of biomolecular interactions for drug discovery.................................. 144
Nanoscale devices for drug discovery ............................................................................ 145
Nanotechnology enables drug design at cellular level....................................................... 145
Nanobiotechnology-based drug development ...............................................................146
Dendrimers as drugs.................................................................................................. 146
Glycodendrimers................................................................................................... 146
Fullerenes as drug candidates...................................................................................... 146
Nanobodies .............................................................................................................. 147
Role of nanobiotechnology in the future of drug discovery ............................................148
Companies using nanobiotechnology for drug discovery ...............................................149
6. Nanobiotechnology in Drug Delivery ................................................. 151
Introduction................................................................................................................151
Micronization versus nanonization for drug delivery......................................................... 151
Nanoscale delivery of therapeutics................................................................................ 151
Nanobiotechnology solutions to the problems of drug delivery ........................................... 151
Nanosuspension formulations ...................................................................................... 152
Ideal properties of material for drug delivery.................................................................. 152
Nanomaterials and nanobiotechnologies used for drug delivery.......................................... 153
Nanoparticle-based drug delivery.................................................................................154
Gold nanoparticles as drug carriers............................................................................... 154
Calcium phosphate nanoparticles.................................................................................. 155
Cyclodextrin nanoparticles for drug delivery ................................................................... 155
Dendrimers for drug delivery ....................................................................................... 155
DNA-assembled dendrimers for drug delivery ............................................................ 156
Polymer nanoparticles................................................................................................ 156
Chitosan nanoparticles........................................................................................... 156
Polymeric micelles ................................................................................................ 157
Ceramic nanoparticles................................................................................................ 157
Nanocrystals............................................................................................................. 158
Nanocrystalline silver............................................................................................. 158
Elan's NanoCrystal technology................................................................................. 158
Eurand's Biorise system ......................................................................................... 159
Nanoparticles bound together in spherical shapes............................................................ 160
Trojan nanoparticles .................................................................................................. 160
Therapeutic protein delivery from nanoparticle aggregates................................................ 161
Drug delivery using “Particle Replication in Nonwetting Templates”..................................... 161
Liposomes...................................................................................................................162
Liposomes incorporating fullerenes............................................................................... 162
Delivery of siRNA by nanosize liposomes........................................................................ 162
Lipid nanoparticles..................................................................................................... 163
Polymerized Liposomal Nanoparticle......................................................................... 164
Stabilization of phospholipid liposomes using nanoparticles.......................................... 164
Applications of lipid nanoparticles ............................................................................ 165
Lipid nanocapsules................................................................................................ 165
Lipid emulsions with nanoparticles ........................................................................... 165
Nanostructured organogels.......................................................................................... 166
Ethosomes for transdermal drug delivery....................................................................... 167
Nanospheres...............................................................................................................167
Nanosphere protein cages........................................................................................... 168
Nanovesicle technology for delivery of peptides ...........................................................168
Nanotubes...................................................................................................................168
Lipid-protein nanotubes for drug delivery....................................................................... 169
Carbon nanotubes for drug delivery .............................................................................. 170
Nanocochleates...........................................................................................................170
Nanobiotechnology and drug delivery devices ..............................................................171
Coating of implants by ultr afine layers of polymers.......................................................... 171
Nano-encapsulation ................................................................................................... 171
Polymer nanocontainers......................................................................................... 172
Mirocontainer delivery systems for cell therapy............................................................... 173
Nanopore membrane in implantable titanium drug delivery device ..................................... 173
Measuring the permeability of membranes................................................................ 173
Nano-valves for drug delivery ...................................................................................... 174
Nanochips for drug delivery......................................................................................... 174
Nanobiotechnology for vaccine delivery .......................................................................175
Bacterial spores for delivery of vaccines......................................................................... 175
Nanoparticles for DNA vaccines.................................................................................... 175
Proteosomes™ as vaccine delivery vehicles .................................................................... 175
Nanobiotechnology for antisense drug delivery ............................................................175
Antisense nanoparticles .............................................................................................. 176
Dendrimers for antisense drug delivery ......................................................................... 176
Polymethacrylate nanoparticles for antisense delivery system............................................ 176
Nanoparticle siRNAi delivery ........................................................................................ 177
Quantum dots to monitor RNAi delivery......................................................................... 177
Nanobiotechnology for gene therapy ............................................................................177
Nanoparticle-mediated gene therapy............................................................................. 178
Nanoparticles as non-viral vectors for CNS gene therapy ............................................. 179
Lipid nanoparticles for targeted delivery of nucleic acids.............................................. 179
Nanoparticles linked to viral vectors for phothermal therapy......................................... 180
Nanoparticles for p53 gene therapy of cancer ............................................................ 180
Immunolipoplex for delivery of p53 gene .................................................................. 180
Intravenous nanoparticle formulation for delivery of FUS1 gene .................................... 181
Silica nanoparticles for gene delivery........................................................................ 181
Gelatin nanoparticles for gene delivery.......................................................................... 182
Calcium phosphate nanoparticles as non-viral vectors ...................................................... 182
Dendrimers for gene transfer.................................................................................. 182
DNA-PEG complexes as nanoparticles....................................................................... 182
Compacted DNA nanoparticles ................................................................................ 183
Cochleate -mediated DNA delivery................................................................................. 183
Dendrimer-based synthetic vector for targeted cancer gene therapy................................... 184
Nanorod gene therapy................................................................................................ 184
NanodelÔ gene vector................................................................................................ 185
NanoNeedles for delivery of genetic material into cells ..................................................... 185
Nanomachines for gene delivery................................................................................... 185
Application of pulsed magnetic field and superparamagnetic nanoparticles........................... 185
Nanocomposites for gene therapy................................................................................. 186
Nonionic polymeric micelles for oral gene delivery ........................................................... 186
Nanocarriers for simultaneous delivery of multiple anticancer agents .................................. 186
Nanobiotechnology-based transdermal drug delivery....................................................187
Delivery of nanostructured drugs from transdermal patches.............................................. 187
NanoCyte transdermal drug delivery system................................................................... 187
Nanobiotechnology-based drug delivery in cancer........................................................188
Nanoparticle formulations of paclitaxel ..................................................................... 189
Pegylated nanoliposomal formulation ....................................................................... 189
Folate-linked nanoparticles..................................................................................... 190
Rerouting lipoprotein nanoparticles to cancer-associated receptors ................................ 190
Carbon magnetic nanoparticles for targeted drug delivery in cancer............................... 190
Gold nanoparticles for targeted drug delivery in cancer................................................ 191
Nanoparticles for targeted delivery of drugs into the cancer cells................................... 191
Non-aggregating nanoparticles................................................................................ 192
Protosphere nanoparticle technology ........................................................................ 192
Perfluorocarbon nanoparticles................................................................................. 193
Nanoparticles containing albumin and antisense oligonucleotides................................... 193
Targeted drug delivery with nanoparticle-aptamer bioconjugates................................... 193
Micelles for drug delivery in cancer .......................................................................... 194
Dendrimers for anticancer drug delivery ................................................................... 195
Application of dendrimers in boron neutron capture therapy ......................................... 195
Application of dendrimers in photodynamic therapy .................................................... 196
Fullerenes for enhancing tumor targeting by antibodies.................................................... 196
Other nanoparticles as adjuncts to photodynamic therapy of cancer............................... 197
Lipid based nanocarriers ........................................................................................ 197
Anticancer drug particles incorporated in liposomes .................................................... 198
Convection-enhanced delivery with nanoliposomal CPT-11........................................... 198
Exosomes............................................................................................................ 198
Cisplatin nanocapsules........................................................................................... 199
Encapsulating drugs in hydrogel nanoparticles ........................................................... 199
Antiangiogenic therapy using nanoparticles ............................................................... 199
Nanocell for targeted drug delivery to tumor.............................................................. 200
Aphios' SuperFluids™ technology............................................................................. 200
Polymersomes for targeted cancer drug delivery ........................................................ 201
Nanodroplets for site -specific cancer treatment.......................................................... 201
Nanocomposite devices.......................................................................................... 202
Nanoengineered silicon for brachytherapy ................................................................. 202
Nanoparticles for boron neutron capture therapy........................................................ 202
Nanoparticles and thermal ablation.......................................................................... 203
Carbon nanotubes for laser-induced cancer destruction ............................................... 203
Nanoparticles combined with ultrasound radiation of tumors......................................... 204
RNA nanotechnology for delivery of cancer therapeutics .............................................. 204
Nanotechnology-based drug delivery to the CNS...........................................................204
Nanoparticle technology for drug delivery across BBB ...................................................... 205
Delivery across BBB using NanoDelÔ technology ........................................................ 205
Nanoparticles for delivery of drugs to brain tumors across BBB ..................................... 205
NanoMed technology to mask BBB-limiting characteristics of drugs................................ 206
Nanotechnology-based devices and implants for CNS ....................................................... 207
Nanotechnology-based delivery to the cardiovascular system .......................................207
Liposomal nanodevices for targeted cardiovascular drug delivery....................................... 207
Anti-restenosis drugs encapsulated in biodegradable nanoparticles..................................... 208
ElectroNanoSpray technology for coating drug-eluting stents............................................. 208
Nano-size ceramic powders for coating drug-eluting stents ............................................... 208
Low molecular weight heparin-loaded polymeric nanoparticles........................................... 208
Injectable peptide nanofibers for myocardial ischemia...................................................... 209
Nanotechnology approach to the vulnerable plaque as cause of cardiac arrest...................... 209
Nanoparticle-based drug delivery to the eye.................................................................209
Nanoparticle-based drug delivery to the inner ear ........................................................211
Nanoparticles for drug delivery to the respiratory system.............................................211
Nasal drug delivery using nanoparticles .......................................................................212
Companies involved in nanobiotechnology-based drug delivery ....................................212
Future prospects of nanotechnology -based drug delivery..............................................215
Nanomolecular valves for controlled drug release ............................................................ 216
7. Clinical Applications of Nanobiotechnology ....................................... 217
Introduction................................................................................................................217
Nanomedicine .............................................................................................................217
Clinical nanodiagnostics ..............................................................................................218
Nano-endoscopy........................................................................................................ 218
Application of nanotechnology in radiology..................................................................... 219
High-resolution ultrasound imaging using nanoparticles.................................................... 219
Nanobiotechnology for developing stem cell-based therapies........................................220
Nanobiotechnology in tissue engineering .....................................................................220
Nanobiotechnology for organ replacement and assisted function ..................................221
Exosomes for drug-free organ transplants...................................................................... 221
Nanobiotechnology and organ-assisting devices .............................................................. 222
Nanotechnology-based human nephron filter for renal failure............................................ 223
Blood-compatible membranes for renal dialysis............................................................... 223
Nanosurgery ...............................................................................................................223
Miniaturization in surgery............................................................................................ 223
Minimally invasive surgery using catheters..................................................................... 224
Nanorobotics ............................................................................................................ 224
Nanoscale laser surgery.............................................................................................. 225
Nano-oncology ............................................................................................................225
Nanobiotechnology for early detection of cancer to improve treatment................................ 225
Impact of nanotechnology-based imaging in management of cancer................................... 226
Nanoparticle-MRI for tracking dendritic cells in cancer therapy...................................... 226
Nanoparticle-CT scan............................................................................................. 226
QDs aid lymph node mapping in cancer .................................................................... 227
Nanosensor device as an aid to cancer surgery .......................................................... 227
Role of nanoparticle-based imaging in oncology clinical trials........................................ 227
Nanoshells for thermal ablation in cancer....................................................................... 228
Nanobody-based cancer therapy .................................................................................. 229
Nanoparticles for targeting tumors................................................................................ 229
Nanoshell-based cancer therapy................................................................................... 230
Nanobomb for cancer ................................................................................................. 230
Combination of diagnostics and therapeutics for cancer.................................................... 231
Targeted therapy with magnetic nanomaterials guided by antibodies ............................. 231
Magnetic nanoparticles for imaging as well as therapy of cancer.................................... 231
Gold nanorods for diagnosis plus photothermal therapy of cancer.................................. 231
A cancer killing device based on nanotechnology............................................................. 232
Nanoparticles for protection against adverse effects of radiation therapy ............................. 232
Role of nanobiotechnology in personalized management of cancer ..................................... 232
Nanobiotechnology for diseases of the nervous system ................................................233
Application of nanotechnology for neuroprotection........................................................... 233
Nanotube-neuron electronic interface............................................................................ 234
Nanowires for monitoring brain activity ......................................................................... 234
Nanoneurosurgery ..................................................................................................... 234
Femtolaser neurosurgery ....................................................................................... 235
Nanofibers as an aid to CNS regeneration by neural progenitor cells .............................. 235
Nanofiber brain implants ........................................................................................ 235
Nanoparticles as an aid to neurosurgery ................................................................... 236
Nanoscaffold for CNS repair.................................................................................... 236
PEBBLEs for brain tumor therapy............................................................................. 237
Bucky balls for brain cancer.................................................................................... 237
Application of nanotechnology to pain therapeutics......................................................238
Cardiovascular diseases...............................................................................................238
Cardiac monitoring in sleep apnea ................................................................................ 238
Detection and treatment of unstable plaques in the arteries .............................................. 238
Nanolipoblockers for atherosclerotic arterial plaques ........................................................ 239
IGF-1 delivery by nanofibers to improve cell therapy for myocardial infarction...................... 239
Tissue engineering and regeneration of the cardiovascular system ..................................... 239
Restenosis after percutaneous coronary angioplasty ........................................................ 240
Nanotechnology -based personalized medicine for cardiovascular disorders.......................... 240
Monitoring for disorders of blood coagulation.................................................................. 241
Orthopedics.................................................................................................................241
Reducing reaction to orthopedic implants ....................................................................... 241
Enhancing the activity of bone cells on the surface of orthopedic implants ........................... 242
Nanobone implants .................................................................................................... 242
Synthetic nanomaterials as bone implants ..................................................................... 243
Carbon nanotubes as scaffolds for bone growth .............................................................. 243
Aligning nanotubes to improve artificial joints................................................................. 243
Nanotechnology as an aid to arthroscopy of cartilage disorders of joints .............................. 244
Scanning force arthroscope .................................................................................... 244
Nanodentistry .............................................................................................................245
Bonding materials...................................................................................................... 245
Dental caries ............................................................................................................ 245
Nanospheres for dental hypersensitivity......................................................................... 246
Ophthalmology............................................................................................................246
Nanobiotechnology and microorganisms ......................................................................247
Nanobiotechnology and virology................................................................................... 247
Study of interaction of nanoparticles with viruses ....................................................... 247
Study of pathomechanism of viral diseases ............................................................... 247
Nanofiltration to remove viruses from plasma transfusion products................................ 247
Role of nanobacteria in human diseases ........................................................................ 248
Nanobacteria and kidney stone formation.................................................................. 248
Nanobacteria in cardiovascular disease..................................................................... 249
Nanotechnology-based microbicidal agents .................................................................... 249
Nanoscale bactericidal powders ............................................................................... 249
Nanotubes for detection and destruction of bacteria.................................................... 249
Carbon nanotubes for protection against anthrax attack .............................................. 250
Nanoemulsions as microbicidal agents ...................................................................... 250
Silver nanoparticle coating as prophylaxis against infection.......................................... 251
Nanotechnology-based vaccines................................................................................... 251
Nanoparticles to combat biological warfare agents........................................................... 252
Nanotechnology for wound healing..............................................................................252
Nanotechnology-based products for skin disorders.......................................................253
Nanoparticles for improving targeted topical therapy of skin.............................................. 253
Topical nanocreams for inflammatory disorders of the skin ............................................... 253
Nanoparticle-based sun screens................................................................................... 253
Cubosomes for treating skin disorders of premature infants. ............................................. 254
Personal care products based on nanotechnology .........................................................254
Nanotechnology for hair care....................................................................................... 255
Nanoparticles for chemo-radioprotection .....................................................................255
Treatment of poisoning and biological attacks ..............................................................256
Nanosuspension formulations for treating bioweapon-mediated diseases ............................. 256
Use of antidotes as nanoparticulate formulations............................................................. 256
Removal of toxins from blood ...................................................................................... 256
Blood substitutes....................................................................................................... 257
Artificial red cells.................................................................................................. 257
Companies using nanotechnology for healthcare..........................................................257
Nanobiotechnology for public health............................................................................259
Nanobiotechnology and nutrition.................................................................................259
Nanobiotechnology and food industry............................................................................ 260
Role of nanobiotechnology in personalized nutrition......................................................... 260
Future potential of nanomedicine.................................................................................260
US Federal funding for nanobiotechnology...................................................................... 261
Nanomedicine initiative of NIH..................................................................................... 261
NCI Alliance for Nanotechnology in Cancer ..................................................................... 262
Research in cancer nanotechnology sponsored by the NCI ................................................ 262
Global Enterprise for Micro-Mechanics and Molecular Medicine ........................................... 265
Nanobiotechnology research in the academic centers....................................................... 265
8. Ethical, Safety and Regulatory issues ............................................... 269
Introduction................................................................................................................269
Ethical, legal and social implications of nanobiotechnology ...........................................269
Nanotechnology standards...........................................................................................269
Safety concerns about nanobiotechnology....................................................................270
Toxicity of nanoparticles............................................................................................. 270
Testing for toxicity of nanoparticles.......................................................................... 271
Quantum dot safety issues..................................................................................... 271
Gold nanoparticle toxicity....................................................................................... 272
Safety of carbon nanotubes in the body......................................................................... 272
Fate of nanoparticles in the human body ....................................................................... 273
Pulmonary effects of nanoparticles ............................................................................... 273
Blood compatibility of nanoparticles .............................................................................. 274
Carbon nanoparticle-induced platelet aggregation....................................................... 274
Compatibility of lipid-based nanoparticles with blood and blood cells.............................. 274
Transfer of nanoparticles from mother to fetus ............................................................... 275
Cytotoxicity of nanoparticles........................................................................................ 275
Nanoparticle deposits in the brain................................................................................. 275
Measures to reduce toxicity of nanoparticles................................................................... 276
A screening strategy for the hazard identification of nanomaterials..................................... 276
Concluding remarks on safety issues of nanoparticles ...................................................... 276
Research into environmental effects of nanoparticles ...................................................277
Role of US government agencies in research on safety of nanoparticles............................... 277
Work at NanoSafety Laboratories Inc UCLA .................................................................... 278
Center for Biological and Environmental Nanotechnology .................................................. 278
Public perceptions of the safety of nanotechnology ......................................................279
Evaluation of consumer exposure to nanoscale materials.................................................. 279
Safety recommendations of the Royal Society of UK .....................................................280
Safety of nanoparticle-based cosmetics........................................................................280
Regulations in the European Union ............................................................................... 280
Nanotechnology-based sunscreens ............................................................................... 281
FDA regulation of nanobiotechnology products.............................................................281
FDA’s Nanotechnology Task Force................................................................................. 283
FDA collaboration with agencies/organizations relevant to nanotechnology .......................... 283
Regulation of nanotechnology in the European Union ...................................................284
9. Nanobiotechnology Markets ............................................................. 285
Introduction................................................................................................................285
Markets according to areas of applications ...................................................................286
Markets for nanomedicine ........................................................................................... 287
Markets for in vitro nanodiagnostics.............................................................................. 287
Imaging agents......................................................................................................... 287
Pharmaceuticals ........................................................................................................ 287
Role of nanobiotechnology in drug delivery market..................................................... 287
Nanobiotechnology in life sciences research market......................................................... 288
Markets according to technologies ...............................................................................288
Markets for nanomaterials........................................................................................... 288
Markets for biomedical nanodevices.............................................................................. 289
Markets for nanotools................................................................................................. 289
Markets for nanosensors............................................................................................. 289
Geographical distribution of markets............................................................................289
Nanobiotechnology in the European Union ...................................................................290
Nano2Life................................................................................................................. 292
Nanobiotechnology in Australia....................................................................................292
Nanobiotechnology in Asia...........................................................................................293
Japan...................................................................................................................... 293
South Korea ............................................................................................................. 294
China ...................................................................................................................... 294
Taiwan .................................................................................................................... 295
India ....................................................................................................................... 295
Nanobiotechnology in Russia.......................................................................................296
Venture capital investment in nanotechnology .............................................................296
Big pharma and nanotechnology ..................................................................................297
Impact of nanobiotechnology on markets for current pharmaceuticals................................. 297
Drivers for the development of nanobiotechnology markets..........................................297
Strategies for developing markets for nanobiotechnology .............................................298
Collaborations of industry with academic research centers................................................ 298
Collaborations of pharmaceutical and nanotechnology companies....................................... 298
Collaboration of chemical industry and the government.................................................... 299
Cost-benefit of nanotechnology-based drug delivery ........................................................ 299
Education of healthcare professionals............................................................................ 299
Education of the public............................................................................................... 300
Unmet needs in nanobiotechnology............................................................................... 300
10. References............................................................................... 301

Tables
Table 1-1: Dimensions of various objects in nanoscale................................................................. 17
Table 1-2: Classification of basic nanobiotechnologies ................................................................. 18
Table 1-3: Historical landmarks in the evolution of nanotechnology................................................ 20
Table 2-1: Companies with nanoliter devices and biochip technologies ........................................... 28
Table 2-2: Applications of optical nanoscopy.............................................................................. 35
Table 2-3: Applications of cantilever technology ......................................................................... 38
Table 2-4: Potential applications of dendrimers in nanobiotechnology............................................. 50
Table 2-5: Nanobiotechnological applications of S-layers.............................................................. 54
Table 2-6: Nanomaterials for biolabeling................................................................................... 57
Table 2-7: Companies providing services and products for nanobiotechnology industry ..................... 60
Table 3-1: Companies that provide nanotechnologies for life sciences research ................................ 93
Table 4-1: Nanotechnologies with potential applications in molecular diagnostics ............................. 96
Table 4-2: Companies developing nanomolecular diagnostics...................................................... 134
Table 5-1: Basic nanobiotechnologies relevant to drug discovery................................................. 139
Table 5-2: Companies involved in nanobiotechnology-based drug discovery and development.......... 149
Table 6-1: Comparison of features of drug delivery by micronization vs nanonization...................... 151
Table 6-2: Nanomaterials and nanobiotechnologies used for drug delivery .................................... 153
Table 6-3: Examples of application of nanoparticles for gene therapy ........................................... 178
Table 6-4: Classification of nanobiotechnology approaches to drug delivery in cancer...................... 188
Table 6-5: Companies involved in nanobiote chnology-based drug delivery .................................... 212
Table 7-1: Nanomedicine in the 21st century ........................................................................... 218
Table 7-2: Companies using nanotechnology for healthcare and therapeutics ................................ 257
Table 7-3: Applications of nanotechnologies in food and nutrition sciences.................................... 259
Table 7-4: Non-commercial institutes/laboratories involved in nanobiotechnology........................... 265
Table 9-1: Markets for nanobiotechnology according to areas of application .................................. 286
Table 9-2: Markets for nanobiotechnology according to areas of application .................................. 288
Table 9-3: Geographical distribution of nanobiotechnology markets 2005-2015.............................. 290
Table 9-4: Drivers for the development of nanobiotechnology markets ......................................... 298
Table 9-5: Strategies for developing markets for nanobiotechnology ............................................ 298
Table 9-6: Cost-benefit of nanotechnology-based drug delivery................................................... 299

Figures
Figure 1-1: Top-down and bottom-up approaches....................................................................... 19
Figure 1-2: Relationship of nanobiotechnology to healthcare and related technologies....................... 21
Figure 2-1: Schematic representation of Dip Pen Nanolithography (DPN) ........................................ 25
Figure 2-2: The core, branching and surface molecules of dendrimers............................................ 49
Figure 2-3: Concept of nanopore-based sequencing .................................................................... 53
Figure 4-1: Scheme of bio-barcode assay................................................................................ 111
Figure 4-2: Scheme of a novel optical mRNA biosensor.............................................................. 123
Figure 4-3: Surface plasmon resonance (SPR) technology .......................................................... 124
Figure 6-1: A lipid nanoparticle.............................................................................................. 164
Figure 6-2: Lipid-protein nanotubes for drug delivery................................................................ 170
Figure 6-3: Cochleate-mediated gene therapy.......................................................................... 184
Figure 6-4: NanodelÔ gene vector ......................................................................................... 185
Figure 7-1: Role of nanobiotechnology in personalized management of cancer............................... 233
Figure 9-1: Components of the $1 trillion market for nanotechnologies in the year 2015.................. 285
Figure 9-2: Nanobiotechnology markets according to applications 2005-2015................................ 286
Figure 9-3: Geographical distribution of nanobiotechnology markets 2005-2015 ............................ 290
Figure 9-4: Unmet needs in nanobiotechnology applications ....................................................... 300

T A B L E O F C O N T E N T S
10. Nanobiotech Companies ..................................................................... 5
Introduction...................................................................................................................5
Classification of companies..............................................................................................5
Profiles..........................................................................................................................5
Collaborations .............................................................................................................224
Tables
Table 10-1: Collaborations in nanobiotechnology...................................................................... 224