Table Of Content

The Handbook of Nanomedicine The Handbook of Nanomedicine Kewal K. Jain MD, FRACS, FFPM JainPharmaBiotech, Basel, Switzerland KewalK.Jain JainPharmaBiotech Basel,Switzerland [email protected] ISBN:978-1-60327-318-3 e-ISBN:978-1-60327-319-0 LibraryofCongressControlNumber:2007940762 (cid:2)c2008HumanaPress,apartofSpringerScience+BusinessMedia,LLC Allrightsreserved.Thisworkmaynotbetranslatedorcopiedinwholeorinpartwithoutthewritten permissionofthepublisher(HumanaPress,999RiverviewDrive,Suite208,Totowa,NJ07512USA), exceptforbriefexcerptsinconnectionwithreviewsorscholarlyanalysis.Useinconnectionwithany form of information storage and retrieval, electronic adaptation, computer software, orby similar or dissimilarmethodologynowknownorhereafterdevelopedisforbidden. Theuseinthispublicationoftradenames,trademarks,servicemarks,andsimilarterms,eveniftheyare notidentifiedassuch,isnottobetakenasanexpressionofopinionastowhetherornottheyaresubject toproprietaryrights. Whiletheadviceandinformationinthisbookarebelievedtobetrueandaccurateatthedateofgoing topress,neithertheauthorsnortheeditorsnorthepublishercanacceptanylegalresponsibilityforany errorsoromissionsthatmaybemade.Thepublishermakesnowarranty,expressorimplied,withrespect tothematerialcontainedherein. Printedonacid-freepaper 987654321 springer.com Preface Nanomedicine is the application of nanobiotechnology to clinical medicine. However, new technologies do not always enter medical practice directly. Nano- biotechnologiesare being used to research the pathomechanism of disease, refine molecular diagnostics, and help in the discovery, development, and delivery of drugs.Insomecases,nanoparticlesarethenanomedicines.Theroleisnotconfined todrugsbeforedevices,andsurgicalproceduresarerefinedbynanobiotechnology, referredtoasnanosurgery. The Handbook of Nanomedicine covers the broad scope of this field. Starting with the basics, the subject is developed to potential clinical applications, many of which are still at an experimental stage. The prefix nano is used liberally and indicates the nanodimension of existing scientific disciples and medical special- ties. Two important components of nanomedicine are nanodiagnostics and nano- pharmaceuticals,whichconstitutethelargestchapters. Keepinginmindthatthereadersofthebookwillincludenonmedicalscientists, pharmaceuticalpersonnel,aswellasphysicians,technologydescriptionsandmedi- calterminologyarekeptassimpleaspossible.Asasingle-authorbook,duplication isavoided.Ihopethatreadersatalllevelswillfinditaconcise,comprehensive,and usefulsourceofinformation. Thereisvoluminousliteraturerelevanttonanomedicine.Selectedreferencesare quotedinthetext. KewalK.Jain,MD Basel,Switzerland v Contents Preface . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . v ListofFigures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xix ListofTables. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xxi ListofAbbreviations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .xxiii 1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 Nanomedicine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 BasicsofNanobiotechnologyinRelationtoNanomedicine . . . . . . . . . . 2 RelationofNanobiotechnologytoNanomedicine.. . . . . . . . . . . . . . . . 4 LandmarksintheEvolutionofNanomedicine . . . . . . . . . . . . . . . . . . . 4 2 Nanotechnologies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 ClassificationofNanobiotechnologies . . . . . . . . . . . . . . . . . . . . . . . . 7 Micro-andNanoelectromechanicalSystems . . . . . . . . . . . . . . . . . . . . 7 BioMEMS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9 MicroarraysandNanoarrays . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9 ProteinNanoarrays . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10 MicrofluidicsandNanofluidics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10 NanotechnologyonaChip . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11 UseofNanotechnologyinMicrofluidics . . . . . . . . . . . . . . . . . . . . . 12 VisualizationandManipulationonNanoscale . . . . . . . . . . . . . . . . . . . 14 AtomicForceMicroscopy. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14 MagneticResonanceForceMicroscopy . . . . . . . . . . . . . . . . . . . . . 15 ScanningProbeMicroscopy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16 Near-FieldScanningOpticalMicroscopy . . . . . . . . . . . . . . . . . . . . 16 MultipleSingle-MoleculeFluorescenceMicroscopy . . . . . . . . . . . . . 17 NanoparticleCharacterizationbyHaloTMLM10Technology . . . . . . . 17 NanoscaleScanningElectronMicroscopy . . . . . . . . . . . . . . . . . . . . 18 OpticalImagingwithaSilverSuperlens . . . . . . . . . . . . . . . . . . . . . 20 vii viii Contents FluorescenceResonanceEnergyTransfer . . . . . . . . . . . . . . . . . . . . 21 4PiMicroscope . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21 PrincipleandApplicationsofCantilevers . . . . . . . . . . . . . . . . . . . . 22 SurfacePlasmonResonance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22 Nanoparticles . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24 QuantumDots. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24 GoldNanoparticles . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26 SilicaNanoparticles . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26 Lipoparticles. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27 AssemblyofNanoparticlesintoMicelles. . . . . . . . . . . . . . . . . . . . . 27 BiomedicalApplicationsofSelf-AssemblyofNanoparticles . . . . . . . 28 ParamagneticandSuperparamagneticNanoparticles . . . . . . . . . . . . . 29 FluorescentNanoparticles . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30 BacterialStructuresRelevanttoNanobiotechnology . . . . . . . . . . . . . 30 Cubosomes. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31 Dendrimers. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32 DNA–NanoparticleConjugates . . . . . . . . . . . . . . . . . . . . . . . . . . . 34 DNAOctahedron. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35 Fullerenes. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35 Nanoshells . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 36 CarbonNanotubes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 37 Nanopores . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 38 NanostructuredSilicon . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 39 NetworksofGoldNanoparticlesandBacteriophage . . . . . . . . . . . . . 39 NanotechnologiesforBasicResearchRelevanttoMedicine. . . . . . . . . . 40 NanoSystemsBiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 40 MolecularMotors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 41 DisguisingQuantumDotsasProteinsforCellEntry . . . . . . . . . . . . . 45 ApplicationofNanolasersinLifeSciences . . . . . . . . . . . . . . . . . . . . . 46 Nanogenomics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 47 DNANanotechnology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 47 RNANanotechnology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 48 RoleofNanobiotechnologyinIdentifying Single-NucleotidePolymorphisms . . . . . . . . . . . . . . . . . . . . . . . . 49 ClinicalNanoproteomics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49 MultiphotonDetection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 50 NanoflowLiquidChromatography . . . . . . . . . . . . . . . . . . . . . . . . . 50 High-FieldAsymmetricWaveformIonMobilityMassSpectrometry . . 50 NanoproteomicsforStudyofMisfoldedProteins . . . . . . . . . . . . . . . 51 UseofNanotubeElectronicBiosensorinProteomics . . . . . . . . . . . . 51 StudyofProteinSynthesisandSingle-MoleculeProcesses. . . . . . . . . 52 NanofilterArrayChip. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 53 StudyofSingle-MembraneProteinsatSubnanometerResolution . . . . 54 Nanoparticle–ProteinInteractions. . . . . . . . . . . . . . . . . . . . . . . . . . 54 Self-AssemblingPeptideScaffoldTechnologyfor3DCellCulture . . . 54 Contents ix NanobiotechnologyforStudyofMitochondria . . . . . . . . . . . . . . . . . . 55 NanomaterialsfortheStudyofMitochondria. . . . . . . . . . . . . . . . . . 56 StudyofMitochondriawithNanolaserSpectroscopy. . . . . . . . . . . . . 56 NanobiotechnologyandIonChannels . . . . . . . . . . . . . . . . . . . . . . . . 57 AquaporinWaterChannels . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 57 NanotechnologyandBioinformatics . . . . . . . . . . . . . . . . . . . . . . . . . 58 3DNanomapofSynapse. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 59 Nanomanipulation.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 59 NanomanipulationbyCombinationofAFMandOtherDevices . . . . . 60 SurgeryonLivingCellsUsingAFMwithNanoneedles . . . . . . . . . . . 60 OptoelectronicTweezers. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 61 3 NanomolecularDiagnostics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 63 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 63 Nanodiagnostics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 64 RationaleofNanotechnologyforMolecularDiagnostics . . . . . . . . . . 64 NanoarraysforMolecularDiagnostics . . . . . . . . . . . . . . . . . . . . . . . . 64 NanoProTMSystem . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 65 Nanofluidic/NanoarrayDevicestoDetect aSingleMoleculeofDNA . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 66 Self-AssemblingProteinNanoarrays . . . . . . . . . . . . . . . . . . . . . . . 67 Fullerene Photodetectors for Chemiluminescence Detection onMicrofluidicChips . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 68 ProteinMicroarrayforDetectionofMoleculeswithNanoparticles . . . 68 ProteinNanobiochip . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 68 NanoparticlesforMolecularDiagnostics . . . . . . . . . . . . . . . . . . . . . . 69 GoldNanoparticles . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 69 QuantumDotsforMolecularDiagnostics . . . . . . . . . . . . . . . . . . . . 70 MagneticNanoparticles . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 73 UseofNanocrystalsinImmunohistochemistry.. . . . . . . . . . . . . . . . 76 ImagingApplicationsofNanoparticles . . . . . . . . . . . . . . . . . . . . . . 76 StudyofChromosomesbyAtomicForceMicroscopy. . . . . . . . . . . . . . 81 ApplicationsofNanoporeTechnologyforMolecularDiagnostics. . . . . . 81 DNA–ProteinandDNA–NanoparticleConjugates . . . . . . . . . . . . . . . . 82 ResonanceLightScatteringTechnology . . . . . . . . . . . . . . . . . . . . . . . 83 DNANanomachinesforMolecularDiagnostics. . . . . . . . . . . . . . . . . . 84 NanobarcodesTechnology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 84 NanobarcodeParticleTechnologyforSNPGenotyping . . . . . . . . . . . 85 QdotNanobarcodeforMultiplexedGeneExpressionProfiling . . . . . . 85 BiobarcodeAssayforProteins. . . . . . . . . . . . . . . . . . . . . . . . . . . . 86 Single-MoleculeBarcodingSystemforDNAAnalysis . . . . . . . . . . . 87 Nanoparticle-BasedColorimetricDNADetectionMethod. . . . . . . . . . . 88 SNPGenotypingwithGoldNanoparticleProbes . . . . . . . . . . . . . . . 88 Nanoparticle-BasedUp-ConvertingPhosphorTechnology. . . . . . . . . . . 89 Surface-EnhancedResonantRamanSpectroscopy . . . . . . . . . . . . . . . . 89 x Contents Near-Infrared(NIR)-EmissivePolymersomes . . . . . . . . . . . . . . . . . . . 90 NanobiotechnologyforDetectionofProteins . . . . . . . . . . . . . . . . . . . 91 CaptamerswithProximityExtensionAssayforProteins . . . . . . . . . . 91 Nanobiosensors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 91 CantileversasBiosensorsforMolecularDiagnostics. . . . . . . . . . . . . 92 CarbonNanotubeBiosensors. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 95 FRET-BasedDNANanosensors. . . . . . . . . . . . . . . . . . . . . . . . . . . 97 IonChannelSwitchBiosensorTechnology . . . . . . . . . . . . . . . . . . . 97 ElectronicNanobiosensors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 97 ElectrochemicalNanobiosensors . . . . . . . . . . . . . . . . . . . . . . . . . . 98 QuartzNanobalanceBiosensors. . . . . . . . . . . . . . . . . . . . . . . . . . . 99 ViralNanosensors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 99 PEBBLENanosensors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 100 Microneedle-MountedBiosensors . . . . . . . . . . . . . . . . . . . . . . . . . 100 OpticalBiosensors. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 100 Nanowire(NW)Biosensors. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 105 NanoscaleErasableBiodetectors . . . . . . . . . . . . . . . . . . . . . . . . . . 107 FutureIssuesintheDevelopmentofNanobiosensors . . . . . . . . . . . . 108 ApplicationsofNanodiagnostics . . . . . . . . . . . . . . . . . . . . . . . . . . . . 109 NanotechnologyforDetectionofBiomarkers. . . . . . . . . . . . . . . . . . 109 PerfluorocarbonNanoparticlestoTrackTherapeuticCellsInVivo . . . 110 MonitoringofImplantedNeuralStemCellsLabeledwithNanoparticles110 NanobiotechnologiesforSingle-MoleculeDetection . . . . . . . . . . . . . 111 Protease-ActivatedQuantumDotProbes . . . . . . . . . . . . . . . . . . . . . 111 NanotechnologyforPoint-of-CareDiagnostics. . . . . . . . . . . . . . . . . 112 NanodiagnosticsfortheBattleField . . . . . . . . . . . . . . . . . . . . . . . . 114 NanodiagnosticsforIntegratingDiagnosticswithTherapeutics. . . . . . 114 ConcludingRemarksAboutNanodiagnostics . . . . . . . . . . . . . . . . . . . 115 FutureProspectsofNanodiagnostics . . . . . . . . . . . . . . . . . . . . . . . . . 116 4 Nanopharmaceuticals . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 119 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 119 NanobiotechnologyforDrugDiscovery . . . . . . . . . . . . . . . . . . . . . . . 119 GoldNanoparticlesforDrugDiscovery. . . . . . . . . . . . . . . . . . . . . . 120 UseofQuantumDotsforDrugDiscovery . . . . . . . . . . . . . . . . . . . . 120 NanolasersforDrugDiscovery . . . . . . . . . . . . . . . . . . . . . . . . . . . 120 CellsTargetingbyNanoparticleswithAttachedSmallMolecules . . . . 121 RoleofAFMforStudyofBiomolecularInteractions forDrugDiscovery . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .121 NanoscaleDevicesforDrugDiscovery . . . . . . . . . . . . . . . . . . . . . . 122 NanotechnologyEnablesDrugDesignatCellularLevel . . . . . . . . . . 123 Nanobiotechnology-BasedDrugDevelopment.. . . . . . . . . . . . . . . . . . 123 DendrimersasDrugs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 123 FullerenesasDrugCandidates. . . . . . . . . . . . . . . . . . . . . . . . . . . . 124 Nanobodies. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 125 RoleofNanobiotechnologyintheFutureofDrugDiscovery . . . . . . . . . 126 Contents xi NanobiotechnologyinDrugDelivery . . . . . . . . . . . . . . . . . . . . . . . . . 127 NanoscaleDeliveryofTherapeutics . . . . . . . . . . . . . . . . . . . . . . . . 127 NanobiotechnologySolutionstotheProblemsofDrugDelivery . . . . . 127 NanosuspensionFormulations . . . . . . . . . . . . . . . . . . . . . . . . . . . . 128 NanotechnologyforSolubilizationofWater-InsolubleDrugs . . . . . . . 129 ImprovedAbsorptionofDrugsinNanoparticulateForm . . . . . . . . . . 129 IdealPropertiesofMaterialforDrugDelivery . . . . . . . . . . . . . . . . . 129 NanomaterialsandNanobiotechnologiesUsedforDrugDelivery . . . . 130 VirusesasNanomaterialsforDrugDelivery . . . . . . . . . . . . . . . . . . . . 131 Nanoparticle-BasedDrugDelivery . . . . . . . . . . . . . . . . . . . . . . . . . . 132 GoldNanoparticlesasDrugCarriers. . . . . . . . . . . . . . . . . . . . . . . . 132 CalciumPhosphateNanoparticles . . . . . . . . . . . . . . . . . . . . . . . . . 133 CyclodextrinNanoparticlesforDrugDelivery . . . . . . . . . . . . . . . . . 133 DendrimersforDrugDelivery . . . . . . . . . . . . . . . . . . . . . . . . . . . . 134 FullereneConjugateforIntracellularDeliveryofPeptides . . . . . . . . . 135 PolymerNanoparticles . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 135 CeramicNanoparticles . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 136 Nanocrystals . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 137 NanoparticlesBoundTogetherinSphericalShapes . . . . . . . . . . . . . . 138 EncapsulatingWater-InsolubleDrugsinNanoparticles . . . . . . . . . . . 139 TrojanNanoparticles . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 140 Self-AssemblingNanoparticlesforIntracellularDrugDelivery. . . . . . 141 ParticleReplicationinNonwettingTemplates . . . . . . . . . . . . . . . . . 141 FlashNanoPrecipitation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 142 NanoparticleCombinationsforDrugDelivery . . . . . . . . . . . . . . . . . 143 Liposomes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 145 LiposomesIncorporatingFullerenes . . . . . . . . . . . . . . . . . . . . . . . . 146 PolymerizedLiposomalNanoparticle . . . . . . . . . . . . . . . . . . . . . . . 146 StabilizationofPhospholipidLiposomesUsingNanoparticles . . . . . . 146 ApplicationsofLipidNanoparticles . . . . . . . . . . . . . . . . . . . . . . . . 147 Liposome–NanoparticleHybrids . . . . . . . . . . . . . . . . . . . . . . . . . . 149 Nanospheres. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 149 NanosphereProteinCages. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 149 NanovesicleTechnologyforDeliveryofPeptides. . . . . . . . . . . . . . . . . 149 Nanotubes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 150 Lipid–proteinNanotubesforDrugDelivery . . . . . . . . . . . . . . . . . . . 151 SingleWallCarbonNanotubesforDrugDelivery . . . . . . . . . . . . . . . 151 HalloysiteNanotubesforDrugDelivery . . . . . . . . . . . . . . . . . . . . . 152 Nanocochleates. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 153 Nanobiotechnology-BasedTransdermalDrugDelivery . . . . . . . . . . . . . 154 DeliveryofNanostructuredDrugsfromTransdermalPatches . . . . . . . 154 NanoCyteTransdermalDrugDeliverySystem . . . . . . . . . . . . . . . . . 155 EthosomesforTransdermalDrugDelivery . . . . . . . . . . . . . . . . . . . 155 Nanoparticle-BasedDrugDeliverytotheInnerEar . . . . . . . . . . . . . . . 156 PulmonaryDrugDeliverybyNanoparticles . . . . . . . . . . . . . . . . . . . . 157 NasalDrugDeliveryUsingNanoparticles. . . . . . . . . . . . . . . . . . . . . . 157

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