This document provides an overview of the application of nanotechnology in biomedicine. It discusses how nanoparticles can be used for diagnostic and therapeutic purposes, including for cancer detection and drug delivery. The document describes several types of nanoparticles that are being researched, such as liposomes, polymeric nanoparticles, metallic nanoparticles, and metal oxide nanoparticles. It also discusses some of the methods used to produce nanoparticles and highlights potential safety issues that require further study before clinical use.

1. Chapter- Application of Nanotechnology in Biomedicine
( sarita Maurya)
Abstract-Nanotechnologyisthe developmentof engineereddevicesatthe atomic, molecular
and macromolecular level innanometerrange. Nanoparticleshave potential applicationin
medical fieldincludingdiagnosticsand therapeutics.Nanotechnologydevicesare beingdeveloped
for diagnosisof cancer and infectious diseaseswhichcan helpinearly detectionof the disease.
Advances innanotechnologyalso proved beneficial intherapeuticfieldsuchas drug discovery,
drug deliveryand gene/proteindelivery.Nanoparticlescanbe constructed by various
methodologyso that effectcan be targeted at desiredsite.In this review,some of the applications
of nanoparticlesin medicine asdiagnostics and therapeutics which can be employedsafelyat the
clinical level have beendescribed.On otherhand, as the particles become generally smallertheir
likehoodofcausing harm to the lungincreases.Therefore,there is a needto study safety of
nanoparticles.
Keywords:Cancer, Diagnosis,Drug delivery,Nanoparticles,Nanotoxicity,Therapy.
INTRODUCTION:-
DefinitionandHistory ofNano:-
Nanotechnologyisa broad term that refersto all technologiesinnano-scale.Many nano-scale is
about 1nm to 100nm. (1 nanometeris a billionthof a meter).Nanotechnologyis a fieldofapplied
science,and it covers a wide era of sciences. The main theme of thisbranch of knowledge isto
control devicesor substanceslessthan one micrometerin size.Nanotechnologyisa science to
understandand employthe new propertiesofmaterials and systems at the nano-scale which
shows effectsofmodern physics - mainlyinfluencedbypropertiesof quantum physics.
Nanotechnologyisa multidisciplinaryknowledge,andithas a tendencyto differentsubjectssuch
as medicine, pharmacy, drug design,veterinarymedicine,biology,appliedphysics,materials
engineering,semiconductordevices,supper-molecule chemistry,mechanical,electrical and
chemical engineering.Researchersbelieve thatnanotechnology,biotechnologyandinformation
technology(IT) are the three kingdomsof third ScientificIndustrial Revolution.Nanoand
nanotechnologywas first introducedby Richard Feynmaninearly 1959 (it was not yet named) .
Because he brought up nanotechnologyin a speechentitled"There isplentyof space on the lower
levels”.He offeredthe theorythat we can manipulate moleculesandatoms directly.But the term
nanotechnologywas first introducedin 1974 by ProfessorNorio Taniguchi from Tokyo Science
University.He used the term nano to describe the material or equipmentwithnanometerrange
precisionand accuracy . Anotherbreakthrough in nanotechnologyoccurred in1985 when,Richard
Smalley& Robert Curl and JamesHeath discovered“C60” a soccer ball like carbon made of nano-
ranging pieces. It was a unique molecule called" buckminsterfullerene" butmostlyknownas

2. buckyball that was first designedby“Richard Buckminster "Bucky" Fuller” an American engineer.
It was also an extremelyrugged molecule,whichcouldeasilywithstand whenclashing with metal
and other materials withspeed greater than 20,000 milesperhour. Its unique shape and
roughnessmakes it a potential good candidate for using it infuel chambers of car engines.In
1991, SumioIijima from NEC in Japan discovereda newform of carbon callednanotubes,which
consist ofmany tubesthat are placednext to each other . Two years later, Donald S. Bethune and
others from IBM in the UnitedStates discoveredsingle-wallednanotubeswitha thicknessof 1-2
nm. Nano-tubesbehave like metalsor other semiconductors,but they couldconduct electrons
betterthan copperand heat betterthan diamonds; therfore they were identifiedasstrong solid
materials.One of the most important progressesinthe applicationof nanotechnologywas Dip-
Pennanotechnologyor DPN that was discoveredbyChad A. Mirkin, the Director ofthe
International Institute for Nanotechnologyand Centerfor Nanofabrication and Molecular Self-
Assemblyat NorthwesternUniversity. This ideawas based on an antique quill penof 17th
century. DPN technologyusedto designmetal, chemical or other biological moleculesonthe
nano-scale by using atomic microscopes. Nanotechnologyis classifiedintovarioussectionsand
divisionsas follows:nano-coatings,nano-materials,nano-powders,nano-tubes,nano-compos.
Nanomedicine isthe applicationof nanotechnologyintreatment, diagnosis,monitoringand
control of biological systems,and is at the leading-edge ofclinical medicine andpreclinical
research. Increasingattentionhas beenpaidto the application of nanotechnologyinmedicine
recently.Nanotechnologymeansthe control of matter and processesat a nanoscale (1–100 nm) in
one or more dimensions.The material and devicesoperatedat the nanoscale usually have
differentphysical propertiescomparedwith those at the normal size.Nanomedicine-based
approaches have thus an unprecedentedpotential tobettercontrol biological processesand to
improve the detection,therapyand preventionofmultiple diseases.The applicationsof
nanotechnologyand its safety have become the highlightofcurrent biomedical research.This
paper focuseson the main nanotechnologiesandtheirbiosafetyencounteredinbiomedical
research,diagnosisand therapy. it involvesscientistsfrommany differentareasincluding
physicists,chemists,engineersandbiologists.Inthis review,the emergingtechnologybeing
developedformedical applicationfor diagnostic and therapeuticpurposeshas beenreviewed.
A briefoverviewof nanotechnologyand differenttools ofnanotechnologyavailable for diagnosis
and targeting of diseaseshas beencoveredinthe first section.The secondsectionfocuseson
applicationof nanotechnologyto medicine,whichis the leadingissue in today’s world (i.e.cancer,
contraception,drug delivery).The thirdsectioncomprisesa descriptionof toxicologyof
nanomaterials.ites,nanowires,nano-electronics,nano-sensors,nano-transistors,molecular
engineeringandmolecular.
Life is a seriesof processesin nano-scale inthe cell.So, everypossible structural similaritywith
theirnatural sourcesin livingcellswill allow nanoparticlesto react withbiological moleculeson
the surface or inside the cellsand as results;theywould influence cellularresponsesinadynamic
and selective way.Materials in such dimensionshave attracted much more attentionsfor medical
applications.Several therapeuticoptions at the nano-scale are risingfor the treatment of severe
diseasessuchas cancer . Some featuresof nano-particlessuchas shape,chemical structure and
especiallysize have directlyaffectedtheirbiological operates . Gene delivery,drugtargeting, cell
labeling,biosensor,treatinginhigh temperature condition,imaging,diagnosisand treatment of
cancers are the most important operatesof nano-materialsin medicine .Therapeutic potential of
nano-materialsis the most important applicationsthet,whichhave recentlyattracted more
attentions.Clinical applicationof various forms of nano-materialssuch as nanoparticles,nano-rod,

3. the nanowires,nanotubes,and nano-fibersstudied.The optical,magnetic and biological
propertiesof nanoparticlesare important in the studytheir of biological processesand medical
applications.Role ofnanoparticles inthe clinical treatments; especiallyincancer is rapidlyrising.
Nanoparticlesinduce apoptosis incancer cellsby several mechanisms,comprisingproducingactive
oxygenand oxidative stress.
Different types of nanoparticles used in medicine
1) Liposom Nanoparticle:-
Liposomeswere discoveredin the mid-1960 . Liposomesare spherical nanoparticleswith a bilipid
membrane which are the most important tools in nano-scale drug delivery.It has beenshown
that whenchemotherapydrugs and othertoxic agents such amphotericinB, are deliveredto
tissuesby liposomes the efficacyand safetyof these drugs will be much more than other
conventional methods.One of the most important featuresof liposomesisthat theycan be
designedsothat theycan target a specifictissue or organ. Usingliposome in drug deliveryraises
specificityofdrug actions on tissues;also, it reducesfailuresand side effectsofdrugs on other
tissuesresultsin greater safetyand specificityofdrugs. So the liposome drug deliverysystems
usedto reduce drug toxic and side effectson adjacent tissues.These are spherical vesicleswitha
membrane composedof a lipidbilayercontainingan aqueoussubstance.The amphiphilic
moleculesusedforthe preparation of these vesiclesare similarto biological membranessoas to
improve the efficacyand safety of differentdrugs . The active compound can be hydrophilicand
therefore locatedin the aqueous space or hydrophobic,remainingin the lipidmembrane.The
synthesisof a liposome dependsmainlyonthe followingparameters:(a) the physicochemical
characteristics of the material to be entrappedand those of the liposomal compounds; (b) the
nature of the mediuminwhich the lipidvesiclesare dissolved,the concentrationof the entrapped
substance,and itspotential toxicity; (c) additional processesimplicatedinduring the fabrication,
application,or deliveryofthe vesicles;(d) dispersity,size,andshelf-life ofthe vesiclesforthe
intendedapplication;and (e) batch-to-batch reproducibilityandpossibilityoflarge-scale
production ofsafe and efficientliposomal products.Liposomescan be synthetizedbysonicatinga
dispersionofamphipatic lipids,such as phospholipids,inwater. In fact, low shearrates can create
multilamellarliposomes.The original aggregateshave many layers, thus formingprogressively
smaller,eventuallyunilamellarliposomes.Sonicationisa “gross” methodof preparation,as it can
damage the structure of the drug to be encapsulated.In addition,there are othermethods,such

4. as extrusionand the Mozafari method , whichare employedto produce materialsfor human use.
Finally,it isimportant to mentionthat usinglipidsotherthan phosphatidylcholine cangreatly
facilitate liposome preparation. Liposomesare a class ofwell-establisheddrugcarriers that have
foundnumerous therapeuticapplications.The successof liposomes,togetherwithrecent
advancementsin nanotechnology,has motivatedthe developmentofvariousnovel liposome-like
nanostructures with improveddrug deliveryperformance.These nanostructurescan be
categorizedinto five major varieties,namely:(1) polymer-stabilizedliposomes,(2) nanoparticle-
stabilizedliposomes,(3) core-shell lipid-polymerhybridnanoparticles,(4) natural membrane-
derivedvesicles,and(5) natural membrane coated nanoparticles.They have receivedsignificant
attentionand have become populardrug deliveryplatforms.Herein,we discussthe unique
strengths ofthese liposome-like platformsindrugdelivery,witha particular emphasison how
liposome-inspirednovel designshave ledtoimprovedtherapeuticefficacy,and reviewrecent
progress made by each platform in advancing healthcare.
2) Polymeric Nanoparticles
Most polymericnanoparticlesare known for their biodegradabilityandbiocompatibility,
constitutingthe most commonly used NPsin drug deliverysystems .This type of nanoparticle can
be made from natural polymers,such as chitosan, or syntheticpolymers, such as polylactides
(PLA),poly (methyl methacrylate) (PMMA),or polyethylene glycol (PEG) .Theyexhibitgreat
potential for surface modificationand have a good pharmacokineticprofile in that their size and
solubilitycan be controlledduring manufacture. Polymericnanoparticlescan be preparedby
differentmethods,includingtwo-stepproceduresbasedonemulsification,emulsification-solvent
evaporation,emulsification-solventdiffusion,andemulsification–reverse salting-out.Additionally,
there are methods such as one-stepproceduresinvolvingnanoprecipitationmethods,dialysisand
supercritical fluidtechnology.Among the techniquesusedto analyse surface properties,we can
findenergydispersive spectroscopy(EDS),zeta potential (ζ-potential),X-rayphotoelectron
spectroscopy(XPS), Fouriertransform infraredspectroscopy (FTIR),and Raman. These techniques
reveal the chemical compositionof polymericnanoparticle surface and surface functionalization.
However,only by usingmicroscopic techniquesisit possible to identifymorphologyand shape.
Finally,it isimportant to take into account that, in orderto improve drug-loadingefficiencyand
prolong drug release,the nature of polymer-druginteractions,as well as the polymer type and
itsphysicochemical properties,mustbe considered . Polymericnanoparticles(PNPs) are composed
of various kindsof polymer,usedfor the production of nanocapsulesor nanospheres.Whenthe

5. polymersthat compose the structure ofNPs are biodegradable or nontoxic,many opportunitiesto
employthese systemsarise, mainlyin biomedical applications,suchas potential systemsfor the
controlledrelease ofdrugs, carriers in gene therapy, or guideddrug deliveryto the desiredtissues
or organs .
Kumar etal. developeda biodegradable polymericNPfor oral drug deliveryofquercetin.The
polymerusedwas poly-ɛ-caprolactone (PCL),whichis nontoxic,FDA approved, permeable,
biodegradable,andbiocompatible.The authors concludedthat the particlesallowedthe
controlledrelease ofthe drug, and that theycould further be used inthe pharmaceutical industry.
3) Metallic Nanoparticles-
These include preciousmetals(gold or silver) and magneticmetals (ironoxide or cobalt and
manganese dopedferrites).Metallicnanoparticlessuch as gold (Au) possessunique electronicand
optical propertiesand are nontoxicand biocompatible,andtheir surface can be modifiedwith
other biomoleculesdue totheirnegative charge . A goldsurface offersa fantastic opportunityto
conjugate ligandssuch as proteins,oligonucleotides,andantibodiescontainingfunctional groups
such as phosphines,thiols,mercaptans, and amines,which have a high affinityfor the gold surface
. Goldnanoconjugates coupledwithstrongly enhancedlocalizedsurface plasmon resonance gold
nanoparticleshave applicationsin imagingtechniquesfor the diagnosis ofvarious diseases . In
fact, El-Sayedet al. establishedthe use of gold nanoparticles(AuNPs) forcancer imagingby
selectivelytransportingAuNPs into the cancer cell nucleus,thushighlightingthe importance of
these nanoparticlesin biomedicine.Inorderto do this,they conjugatedarginine–aspartic acid–
glycine peptide and a nuclear localizationsignal peptide to a 30 nm AuNPs. The conjugated
arginine–aspartic acid–glycine peptide targetsαvβ6 integrinreceptorson the surface of the cell,
whereasthe lysine–lysine–lysine–arginine–lysinesequenceassociateswithkaryopherins
(importins) inthe cytoplasm, whichenablestranslocation to the nucleus . Metallicnanoparticles
have fascinatedscientistfor over a century and are now heavilyutilizedinbiomedical sciencesand
engineering.Theyare a focus ofinterestbecause of their huge potential in nanotechnology.Today
these materialscan be synthesizedandmodifiedwithvarious chemical functional groups which
allow themto be conjugatedwith antibodies,ligands,and drugs of interestand thus openinga

6. wide range of potential applicationsin biotechnology,magneticseparation,and preconcentration
of target analytes,targeted drug delivery,and vehiclesforgene and drug deliveryand more
importantly diagnosticimaging. Moreover,variousimaging modalitieshave beendevelopedover
the periodof time such as MRI, CT, PET, ultrasound, SERS, and optical imagingas an aid to image
various disease states.These imaging modalitiesdifferinboth techniquesandinstrumentation
and more importantly require a contrast agent with unique physiochemical properties.Thisledto
the inventionofvarious nanoparticulatedcontrast agent such as magnetic nanoparticles(Fe3O4),
gold,and silvernanoparticlesfor theirapplication in these imagingmodalities.Inaddition, to use
various imagingtechniquesin tandemnewermultifunctional nanoshellsandnanocages have been
developed.Thusinthis reviewarticle,we aim to provide an introductionto magnetic
nanoparticles(Fe3O4),gold nanoparticles,nanoshellsand nanocages,and silvernanoparticles
followedbytheir synthesis,physiochemical properties,andcitingsome recent applicationsin the
diagnosticimaging and therapy of cancer.
4) Metal Oxide Nanoparticles
These NPs exhibitcatalytic and antioxidantactivities,chemical stability,optical properties,and
biocompatibility,all of whichmake them suitable for several biomedical applications.The most
widelyusedare iron oxide (Fe3O4),titania (TiO2), zirconia (ZrO2), and more recently,ceria (CeO2)
. For instance, titania nanoparticlesare incorporated intomedical implants due to the
biocompatibilityoftheir surface,and ceria nanoparticlesare the object of increasingattention
because of theircatalytic and antioxidant capacity, which allowsthem to act as antioxidant and
anti-inflammatoryagents . TiO2 is a widelystudiedmaterial due to itsbiocompatibility,chemical
stability,and optical properties,whichendow it withimportant applications,for instance,as a
biosensor. Other metal oxide nanoparticlesof increasinginterestfor their potential biomedical
applicationsare cerium oxide (CeO2) nanoparticlesor nanoceria. Nanoceria have the unique
property of beingable to switch betweenoxidationstates , therefore enhancingtheirapplication
in oxidative stress-relateddiseases.Ceriumoxide nanoparticleshave many defectson their
surface,mainly O2 vacanciesthat resultin a combinationof coexistingcerium(IV) and cerium (III)
oxidationstates. This leadsto a redoxcouple,which underliesnanoceria’scatalytic activity. These
characteristics endownanoceria with great potential as a biological antioxidant.Other examples
of metal oxide nanoparticlesare porous silica(SiO2).The biomedical applicationsof these
nanoparticlesare increasingdue to their unique properties,whichinclude large specificsurface
area, pore volume,controllable particle size,and good biocompatibility.Itis due to these
propertiesthat mesoporoussilica nanoparticleshave beeninvestigatedfortheiruse indrug
deliveryinbiomedicine andbiosensors . metal oxide nanoparticlesas important technological

7. materials,authors provide a comprehensive reviewofresearcheson metal oxide nanoparticles,
theirsynthetic strategies, and techniques,nanoscale physicochemical properties,definingspecific
industrial applicationsin the various fieldsofappliednanotechnology.Thiswork expansively
reviewsthe recent developmentsofsemiconductingmetal oxide gassensorsfor environmental
gases includingCO2, O2, O3, and NH3; highlytoxicgases includingCO, H2S, and NO2; combustible
gases such as CH4, H2, and liquefiedpetroleumgas;and volatile organic compounds gases.The
gas sensingpropertiesof differentmetal oxidesnanoparticles towards specifictargetgases have
beenindividuallydiscussed.Promisingmetal oxide nanoparticlesforsensitive andselective
detectionofeach gas have beenidentified.
5) Ceramic Nanoparticles
These are inorganic compoundswith porous characteristics that have recentlyemergedasvehicles
for drugs. They are capable of transporting moleculessuchas proteins,enzymes,or drugs without
swellingor compromisingtheirporosity due to the external effectsofpH or temperature . The
componentsmost commonly usedin ceramic nanoparticlesare silica and aluminum.However,the
core of these nanoparticlesis not limitedto these two materials;in fact, they can be composedof
a combinationof metallicand nonmetallicmaterials . For instance, CeO2-cappedmesoporous
silicananoparticles (MSN) have beendevelopedtoact as vehiclesfordrug deliverybyreleasingβ-
cyclodextrininto lungcancer cells .
There are a wide range of ceramic materials withmultiple applications,includingclay minerals,
cement,and glass. Biocompatible ceramics,also known as bioceramics,are mainlyused for the
bone,teeth,and other medical applications.Bioceramics have good biocompatibility,
hydrophilicity,osteoconductivity,biodegradability,andreabsorbability.The most widelyused
ceramic nanobiomaterialsare calcium phosphate (CaP),calcium sulphate and carbonate,
tricalcium phosphate (TCP),hydroxyapatite (HAP), TCP+HAP, bioactive glasses,bioactive glass
ceramics, titania-basedceramics,alumina ceramics,zirconia ceramics, and ceramic polymer
composites.All have beenappliedinnanomedicine,orthopedics,bone regeneration,dentistry,
and tissue development,inadditionto other biomedical usesinthe human body .
Challenges associatedwithnanotechnology

8. Today, Nanotechnologyis gainingimportance in biologydue to its small size and targeted
effects.Nanoscale devicesare 100-10,000 timessmallerthan the human cell.Because of their
small size and larger surface area relative to theirvolume,nanoscale devicescan readilyinteract
with biomolecules(suchasenzymesand receptors) on both, the surface of the cell and inside the
cell.By gaining access to various areas of the body, nanoparticleshave the potential to detect
disease at the micro level anddelivertreatment.Work is currently beingconductedto find ways
to safelymove these newresearch tools into clinical practice . Nanoparticles,forexample can
have multiple functionalitiesthatcan provide detailedinformationon the progressionof disease.
Nanoparticlescan be made from a vast range of materials,such as metals(gold,silver),metal
oxides,[e.g.titaniumdioxide (TiO2),Silicondioxide (SiO2)],inorganicmaterials(carbonnanotubes,
quantum dots),polymericmaterialsand lipids2.The other newsets oftools is available in
nanotechnology are nanocrystals ,cantilevers,dendrimers,nanoshellsandnanowires.These
particlescan range from fewto severalofnanometersin diameter.Products made from each of
these tools can be usedfor diagnosis(asbiomarkers) and therapy.As reportedby Service3
nanotechnologyin just 5years has developedfrombeinga specialtyof physicistsand chemiststo a
worldwide scientificand industrial enterprise.Currentlymost of the researchwork focuseson the
use of nanoparticlesto treat diseasessuch as cancer, HIV and diabetesandas carrier for drug
delivery. Didenkoand Baskin4 have describedan enzymatic approach for labelingnanotubeswith
quantum dots. The labelingwas performedvia enzymaticbiotinylationof nanotubes inthe
tyramide-horseradishperoxidase (HRP) reaction.They achievedbothdirect and indirect
fluorescentlabelingofsingle walledcarbon nanotubes(SWNTs) usingeitherbiotinyltyramide or
fluorescentlytaggedtyramides.Linking semiconductornano crystals, quantum dots (Q-dots) on
the surface of nanotubesresultedin theirfluorescentvisualization,whereasconventional
fluorophoresboundto SWNTsdirectlyor through biotin-streptavidinlinkage were completely
quenched.Usingthisapproach other organic moleculessuchas proteins,antibodiesor DNA can be
conjugatedto biotinylatedSWNTs,whichcould be useful for a number of biomedical applications.
Nanotechnology andits applicationto cancer
Cancer, a major killer disease is a complex sequence starting from diagnosis till
therapy.Currently detection and diagnosis of cancer usually depends on changes in cells
and tissues which occur at the nanoscale level inside the cells and are detected eitherby
physical examination or imaging expertise. Scientists would now like to make it possible
to detet cancer when the earliest molecular changes occur.Detecting cancer at an early
stage before it spreads,completely changes the scenariofor treatment of most cancer.

9. Nanotechnology offers a wealth of tools that provide cancer researchers with new and
innovative ways to diagnose and treat cancer.
National Cancer Institute (NCI) US is working on Nanotechnology in Cancer. NCI has also
established the nanotechnology characterization laboratory, which will develop a cascade
of assays for further product development and regulatory review. Dr. Gregory Downing,
Director of NCI5 has described how nanotechnology can help in product development
from ‘bench to bedside’ and improve drug discovery efforts by addressing the
complexities of cancer.Nanoscale devices can deliver multiple therapeutic agents to a
tumor in order to simultaneously attack multiple points in the pathway involved in
cancer.Similarly, nanotechnology generates in vivo biosensors that have the capability of
detecting and pointing the location of tumor and metastatic changes that are smaller than
those detectable using conventional technologies.
Nanotechnology in biomedical analysis and research
Fluorescence imaging has been widely used in biology and medicine. Single-molecule
detection (SMD) can detect signals from individual molecules, which removes the average
effect in classical ensemble experiments . Besides the confocal fluorescence microscopy,
the main SMD techniques include total internal reflection fluorescence microscopy
(TIRFM), single-molecule fluorescence resonance energy transfer (smFRET), cylindrical
illumination confocal.

10. spectroscopy (CICS), epi-fluorescence microscopy, confocal microscopy, quasi-TIRFM and
single-point edge excitation subdiffraction microscopy (SPEED). SMD techniques are
widely used in membrane protein research. For instance, in the experiment regarding TGF-
beta type II receptors of neonatal rat cardiomyocytes, the dimerized receptors were found
to increase in hypertrophic cardiomyocytes by SMD, which infers the functioning of TGF-
beta signaling in cardiac remodeling. Another study tracked the 1A-adrenergic receptor,
and found that endocyticpathway is involved in 1A-AR-induced ERK1/2 activation, and is
independent of G(q)/PLC/PKC signaling. Moreover, some nanomaterials are potential
florescence probes in relevant technologies. For instance, quantum dots are of high photo
stability, high identification accuracy and controllable colors, and have been used as
fluorescence imaging probes,fluorescent protein FRET probes and molecular beacons .
Nanotechnology in diagnosis
Nanodevicessuchas nanowiresand cantileverscan provide rapid and sensitive detectionof
cancer relatedmoleculesby enablingscientiststodetect molecular changesevenwhen theyoccur
only ina small percentage ofcells.This would helpinearly detection of cancer. The attachment of
nanomaterialsto the molecule ofinterestcan be used as diagnostic markers.The cantileveris one
tool with potential aid in cancer diagnosis.Nanoscale cantilevers-tinybarsanchored at one end
can be engineeredtobindto moleculesassociatedwithcancer. Whenthe cancer associated
molecule bindsto the cantilevers,it changes the surface tensioncausing the cantileverto bend. By
monitoringwhetherthe cantileversare bent and to what extent,scientistscan assess,whether
the cancer moleculesare present.One tool Quantum dot can detect earlyDNA changes in the
body. Quantum dots are tiny crystals that glow whenthey are stimulatedby ultravioletlight.The
wavelengthor color of the lightdependson the size of the crystal. Latex beads filledwiththese
crystals can be designedto bindto specificDNAsequences.Whenthe crystals are stimulatedby
light,the colors theyemit act as dyesthat lightup the sequencesofinterest.By combining

11. differentsize quantumdots withina single bead,researcherscan create probesthat release a
spectrum of variouscolors and intensitiesoflight servingas spectral bar code. To detect cancer,
one can designbeadscontaining quantum dots to bind to the sequence ofDNA that isassociated
with cancerous cells.Researchis underway to findout innovative ways at the nanoscale level
which couldbe useful to detectearly mutagenicchanges.
Nanodevicessuchas nanowiresand cantileverscan provide rapid and sensitive detectionof
cancer relatedmoleculesby enablingscientiststodetect molecular changesevenwhen theyoccur
only ina small percentage ofcells.This would helpinearly detection of cancer. The attachment of
nanomaterialsto the molecule ofinterestcan be used as diagnostic markers.The cantileveris one
tool with potential aid in cancer diagnosis.Nanoscale cantilevers-tinybarsanchored at one end
can be engineeredtobindto moleculesassociatedwithcancer. Whenthe cancer associated
molecule bindsto the cantilevers,it changes the surface tensioncausing the cantileverto bend. By
monitoringwhetherthe cantileversare bent and to what extent,scientistscan assess,whether
the cancer moleculesare present.One tool Quantum dot can detect earlyDNA changes in the
body. Quantum dots are tiny crystals that glow whenthey are stimulatedby ultravioletlight.The
wavelengthor color of the lightdependson the size of the crystal.Latex beadsfilledwiththese
crystals can be designedto bindto specificDNAsequences.Whenthe crystals are stimulatedby
light,the colors theyemit act as dyesthat lightup the sequencesofinterest.By combining
differentsize quantumdots withina single bead,researcherscan create probesthat release a
spectrum of variouscolors and intensitiesoflight servingas spectral bar code. To detect cancer,
one can designbeadscontaining quantum dots to bind to the sequence ofDNA that isassociated
with cancerous cells.Researchis underway to findout innovative ways at the nanoscale level
which couldbe useful to detectearly mutagenicchanges.
Nanotechnology in therapy
Nanomaterials have been introduced to the therapy of multiple diseases, including drug
delivery system and nanodrugs. Drug delivery is one of the typicalapplications of
nanomaterials in medicine. For example, tumor targeting,imaging and drug delivery can
be accomplished by administrated gold nanoparticles and nanorods, iron oxide
nanoworms and drug loaded liposomes . Some other nanomaterials can be used to
decorate gold nanoparticles to improve the capability . The nanotechnology has also been

12. applied to the intelligent drug-delivery systems and implantable drug-delivery systems , so
as to realize the controlled and targeted release of therapeuticdrugs.Besides drug
delivery, nanomaterials have been adopted in some specific tumor therapies. Au
nanoparticles have the potential to be developed as novel contrast agents in
photothermal cancer therapy . They concentrate in the diseased region, absorb light and
convert it into heat to destroy the malignant cells. Gd@C82(OH)22 nanoparticles have
been demonstrated to be a potent antitumor nanomedicine acting on the tumor
microenvironment . They have no direct tumor cytotoxicity, and their antineoplastic
activity is based on the inhibition of oxidation stress and angiogenesis, the activation of
immune reaction, the imprisoning of cancer cells, and the reversing of drug-resistance
combination. Au nanoparticles have similar impact on tumor microenvironment .The
application of nanotechnology has opened a new realm in the advance of regenerative
medicine. The development of nanotechnology offers more opportunities of applying
stem cells in the regeneration of tissues and organs.
After diagnosis when it is time to treat cancer,nanoscale devices have the potential to
improve cancer therapy otherthan the existing conventional (chemotherapy,
radiotherapy) techniques and also to discovernew therapeuticagents. It is useful for
developing ways to eradicate cancer cells without harming healthy, neighboring cells.
Scientists hope to use this technology to create therapeuticagents that can target specific
cells and deliver toxins in a controlled, time released manner. The ultimate goal of
researchers is to find out agents of these nanoparticles which can circulate through the
body, detect cancer associated molecular changes, assist in imaging, release a therapeutic
agent and then monitor the effectiveness of the intervention. It can reduce the
unpalatable side-effects that accompany many current cancer therapies.
One such molecule with potential to link treatment with detection and diagnosis is
known as dendrimer. A useful feature of dendrimer is their branching shape, which
provides a vast surface area so that scientists can attach therapeutic agents or other
biological molecules. A single dendrimer can carry a molecule that can recognize cancer
cells, a therapeutic agent that kills these cells and a molecule that recognizes the signals of
cell death. Majoros et al . have reported dendrimer based multifunctional cancer
therapeutic conjugates, which have been designed and synthesized by them. The
functional molecule FITC (an imaging agent), folic acid (FA, targets overexpressed folate
receptors on specific cancer cells) and palcitaxel (taxol, a chemotherapeutic drug) were
conjugated to the dendrimers. These dendrimer conjugates have been tested in vitro for
targeted delivery of chemotherapeutic and imaging agents to specific cancer cells. This
experiment has shown that only cells containing the folic acid receptor took up the
dendrimer and was highly toxic to the cells. In contrast, the dendrimer construct had no
effect on the cells without the folic acid receptor. Dr Hawkins, Chief Medical Officer of
American Bioscience, on the basis of clinical trials , found that Abraxane is safer and more
effective than Taxol in treating patients with breast cancer who had failed earlier
therapies. He also showed that Abraxane is also effective at treating lung cancer and
metastatic melanoma. Nanoshells, another recent invention, are miniscule beads coated
with gold. These beads can be designed to absorb specific wavelength of light. The most

13. useful nanoshells are those which can easily penetrate several centimeters of human
tissue. The absorption of light by the nanoshells creates an intense heat that is lethal to
the cells. Researchers can link nanoshells to antibodies that recognize cancer cells. Metal
nanoshells which are intense near-infrared (NIR) absorbers are effective both in vivo and
in vitro on human breast carcinoma cells.
Application of nanotechnology in drug delivery
Currently, the most promising consequence of the application of nanotechnology, with
respect to medicine, is of drug delivery. The major problem with most of the new chemical
entities is their insolubility.Therefore the first principal aim of nanotechnology is to
improve their solubility and bioavailability. The second is to enhance the release rate of
the drug. Due to these reasons nanotechnology has focused on targeted drug delivery and
controlled drug release. A targeted drug delivery system can convey drugs more
effectively, increase patient compliance and extend product life cycle. According toDubin,
drugs tend to perform more effectively in nanoparticulate form and with fewer side-
effects. Further, specific nanosized receptors present on the surface of a cell can recognize
the drug and elicit an appropriate response, by delivering and releasing therapy exactly
wherever needed. Thus drugs can be loaded via encapsulation, surface attachment or
entrapping. The architecture of nanoparticles, material, drug type and targeted location
can determine the attachment technique. Encapsulated drugs can be protected from
degradation. The drug may be in particles with coating only a few nanometers in
thickness. Drugs are normally ingested or implanted and designed to deliver a controlled
release of drug, which may last for many months and can be activated at different sites in
the body. Nanopores can act as tiny particles for releasing drugs. By making the
nanopores only slightly larger than the molecules of drugs, they can control the rate of
diffusion of the molecules, keeping it constant, regardless of the amount of drug
remaining inside a capsule. Drugs in such a nanocrystalline form can be administered in
smaller doses because they can be delivered directly tothe tissue and in controlled doses.
In this section we summarize different types of nanoparticles which are under
investigation and can be useful for drug delivery systems and their prospective
therapeutic applications. Due to poor water solubility of drugs, therapeutic drugs can be

14. nanosized in the range of 100-200 nm. Larger particles of drugs cannot enter the tumor
pores while nanoparticles in the range of 50-100 nm can easily move into a tumor which
would be useful in cancer treatment. Polymers such as polylactide, poly lactide co-
glycolide (PLG), poly acrylates etc. can be used to coat nanoparticles which can be useful
as a drug carrying device. The use of magnetic nanoparticles in targeted drug delivery
systems is under investigation by several research groups. Therapeutic drug molecules
have been immobilized on the surface of magnetic nanoparticles or nanocrystals and
directed to specific targeted tissue using a magneticfield gradient. The drug is released by
radio frequency (RF) pulse and if magnetic field is applied, nanoparticles become heated,
causing destruction of the cancerous cells. Gold coated iron, nickel or cobalt
ferromagnetic nanoparticles have been employed in this “tag and drag” method. To
improve oral drug delivery one study reports the use of two anti-fungal drugs clotrimazole
and econazole. Each drug was encapsulated in nanoparticles of a syntheticpolymer(PLG)
or a natural polymer (alginate stabilized with chitosan). The formulations were orally
administered to mice and the drugs were analyzed in plasma by a validated HPLC
technique. There was a controlled drug release for 5-6 days with each of the formulations,
compared with unencapsulated drugs, which were cleared within 3– 4 hr of
oral/intravenous administration. Further, the drugs were detected in tissues (lungs, liver
and spleen) until 6-8 days in case of nanoparticles whereas free drugs were cleared by 12
hr. Buxton has discussed some of the more promising targets for nanotechnology-based
treatment of heart, lung and blood diseases. Yih and Al-fandihave described different
types of nanoparticles drug delivery systems under investigation and their prospective
therapeutic applications. Recently Ferrari’s work on porous nanocontainers has been
referred by Service. These containers can be used to ferry compounds to a site anywhere
in the body. Although, he cautions that it could take years to prove safety and efficacy of
these containers.
The biosafety of nanotechnology
Biosafety is mostly concerned in nanotechnological applications. It is important to better
understanding the metabolic fate and biological effect in cells or organs as increasing
nanomaterials are hopeful materials to be applied in medicine. The toxicity of most
nanomaterials applied in biomedicine has been examined in preclinical research in that
the low toxicity and optimal biocompatibility are necessary for their clinical applications.
Gd@C82(OH)22 nanoparticles have no discernible toxic effects either in vitro orin vivo
.Carbon nanotubes (CNTs) are nanomaterials widely applied in biomedicine. However, the
high cytotoxicity limits their use in humans. Water-soluble single-walled carbon
nanotubes and fullerene C70(C(COOH)2) exerted more serious adverse effects on BY-2
cells . Gold nanoparticles are considered to be relatively safe as elemental Au is highly
inert. However, some study found it was hazardous in some cases . However, those
undesired side effects can be avoided by simply changing the capping agents. The
functionalization of CNTs can improve their solubility and biocompatibility, and change
the interaction with cells, resulting in reduced cytotoxicity .The cell uptake and metabolic

15. fate of nanomaterials were also studied. The cellular uptake of nanoparticles depended
on the time of incubation and the concentration of nanoparticles in the medium. Up-
taken CNTs are shown to traffic through the different cellularbarriers by energy-
independent mechanisms . SPIONs entered cells through multiple endocytic pathways and
be subsequently passaged to daughter cells, degraded in the lysosome, or exocytosed out
of the cells . In this process, SPIONs did not induce cell damage, except for the effect on
iron metabolism. Better understanding of the nanomaterial metabolic pathways will
contribute to the development of nanobiology and advocate the secure use of
nanotechonology in medicine.
Nanoparticle toxicity is routinely assessed in cultured cells in vitro. The data from these
studies require verification from animal experiments, as they could be inconsistent and
misleading . Thus it is important to clarify the reliability of cell nanoparticle toxicity
assessment. Whether the excessive subculture could disturb the response of cultured cells
to nanoparticles was studied, so as to obtain consistent toxicity test results. The
investigators compared the cellular responses to silver nanoparticles across multiple
passage numbers in Ba/F3-BCR-ABL cells . The action of culture was not found to affect
the cell response if the cultured cells were maintained in optimal state. Thus, it is
suggested that cells isolated from normal tissues should be applied in the study of
nanomaterials exposure on cells. It is highly promising that nanotechnologies be applied
in biomedicine . Nanomaterial-based contrast agents in molecularimaging usually have
higher sensitivity and possibly fewer side-effects, and can circulate in the blood for longer
time. They are also potential prominent drug carriers in the research, diagnosis and
therapy of multiple diseases, and are potential cancerdrugs targeting on the tumor
microenvironment. The unique property of nanomaterials for drug delivery and
antineoplastic function highlights the new drug development in the future. Therefore the
nanomaterial biosafety needs to be assessed systematically. What’s more,
nanotechonologies applied in basic biomedical research create a novel platform at the
nano-scale to study and develop novel therapies for multiple diseases.
Targets of nanotechnology in contraception
Between the years 1980 and 2000 total world population increased from 4 billion toabove
6 billion and if this trend continues, by 2025 it will reach to 8 billion. Overpopulation is
particularly acute in economically developing countries where contraception has become
a social necessity. In most of the countries a number of methods for contraception are
available over the counter. Oral contraception is popular in western world while IUDs are
preferred in many of the developing countries. Injectables and implants are not available
in all the countries. Sterilization, vasectomy and tubectomy, after the birth of 2-3 children
have been opted by couples. Yet, barrier methods such as condoms are advocated for
birth control as well as prevention of HIV, which is one of the major problems in Southeast
Asia and Africa. The inherent link between brain and reproductive function is well
recognized. Therefore the contraceptives such as orals, injectables, implants which act
through parental route may cause sideeffects than the barrier methods such as condoms,
vaginal pessaries and creams. Use of contraceptives should not only prevent unwanted

16. pregnancies but also benefit the individual to maintain good health. This can be achieved
by targeting the organ or tissue such as vaginal contraceptives containing spermicides.
Nanotechnology may be an ideal device for targeting contraception. A drug which is
effective in blocking fertilization can be targeted at oviduct/fallopian tube level while an
anti-implantation drug can be targeted at uterine level to prevent pregnancy without
interfering with otherorgans or systems of the body. Studies with a peptide, FSH binding
inhibitor (FSHBI) purified from human ovarian follicularfluid have revealed contraceptive
effect in mouse and monkeys. At present preliminary studies have been initiated in our
laboratory to elucidate possible use of nanoparticles on FSHBI.
Nanotoxicity
Although the area of nanotechnology is exciting,safety of this innovative technology
should be tested. Due to the small size and large surface area nanoparticles exhibit
greater biological activity per given mass compared tolarge particles. Nanostructure is so
small that the body may clear them rapidly for them tobe effective in detection and
imaging. On the other hand, large nanoparticles may accumulate in vital organs, thus
creating a toxicity problem. Scientists may need to consider factors how nanostructure
will behave in human body and how the body will accept it. The increased activity of
nanoparticles can be either positive or desirable (e.g. carrier capacity for therapeutics,
penetration of cell barriers for drug delivery) or negative and undesirable (e.g. toxicity,
induction of oxidative stress or of cellular dysfunction) or a combination of both.
Therefore priority should be given to the safety evaluation of nanoparticles as their
applications in medicine are increasing. Research on nanotoxicology will provide data for
safety evaluation of nanostructures and devices and it will also help in the field of
nanomedicine by providing information regarding their undesirable effect. The need for
nanotoxicity research and funding has been recite rated by Service21. On the
international front, Organization for Economic Cooperation and Development (OECD)
members are considering setting up a permanent working group on establishing
international nanotoxicology priorities.
Indian scenario
Considering broad scope of nanotechnology worldwide, research efforts need to be
accelerated in India. Bhath as explored the recent developments and industrial progress in
this field. She has also stressed implementation of nanotechnology in our nation. Some of
the research groups in our country are working on liposome as a drug delivery system in
different experimental models. It is seen that other countries like United States, Europe
are serious about strong knowledge base in this area and spending millions of dollars and
euros on nanotechnology. We in India should take appropriate steps to promote research
and industries in nanotechnology. Companies such as Yashnanotech, Mumbai have
initiated global network, to commercialize and explore local technology. Also the research
institutes such as Indian Institute of Science, Bangalore and Indian Institute of Technology,
Mumbai have conducted workshops and seminars on nanotechnology toencourage
scientists and technologists in this upcoming field. Amity Institute of Nanotechnology,

17. Noida, in India has started M.Tech course in Nanotechnology from November 2003.
Government of India has invested 100 crores for the next 5 years on nanotechnology
research and developments. Considering the importance and developments of this new
frontier area, our scientists should be motivated for application of nanotechnology in
clinical use which is still at laboratory level. Government should take initiative in starting
nanotechnology courses at the undergraduate and graduate levels so that specialist in
nanotechnology can emerge. Looking at global scenario; it is high time that Indian
government forges a nanotechnology policy in tune with the specific needs of the country
and its existing strength.
Nanotechnology and treatment of Immune deficiencies following
cancer treatment
Immune deficiencies following cancer treatment with different chemotherapy drugs such
as doxorubicin lead to development of infectious diseases. Use of traditional antibiotics
such as penicillin causes development of resistant microbial strains. With increasing
antibiotic resistant microbial strains, the discovery of new antimicrobial compounds has
been of double significance. Researchers have approved that the nanostructures have a
broad-spectrum of antimicrobial activities against different pathogens (Gram negative and
Gram positive bacteria, fungal pathogens) such as human gut bacteria, Escherichia coli,
Bacillus subtilis, Candida tropicalis, Staphylococcus aureus, Salmonella enteric,
Enterococcus faecium etc. Recent results have shown that different metal nanoparticles
and nanotubes can be promising alternative to antibiotics for annihilation of multidrug-
resistant bacterial strains. Nowadays, nanostructures are considered as a new candidate
for inhibition of microbialgrowth in the different media. Mass production of numerous
nanomaterials with good antibacterial activities such as metal and metal oxide
nanoparticles (silver (Ag), silver oxide (Ag2O), titanium dioxide (TiO2), zinc oxide (ZnO),
gold (Au), calcium oxide (CaO), silica (Si), copper oxide (CuO), and magnesium oxide (MgO)
provide suitable changed applicable condition. So, these nanostructures are one benefit
candidates for prevention of infections in patients with immunodeficiency.
Among these aforementionedstructures,CNTs(MWCNTsand SWCNTs) are more suitable in terms
of antimicrobial activitiesin comparison with other nanostructures. So, these nanotubesare the
antimicrobial agents to inhibitthe microbial growth in differentenvironments.Ithas beenproven
that CNTsexhibithigh antimicrobial activity. Differentstudiesindicatedthat single-walledcarbon
nanotubes(SWCNTs) and multi-walledcounterparts(MWCNTs) showedunique antimicrobial
properties. Differentfactors influence the antimicrobial activitiesofCNTs. Thus, the antimicrobial
activity of CNTs was not equal indifferentforms,size,chemical characteristics, and environments .
Because of immunodeficiencyinpatientswithcancer disease,the isolatedenvironmentsare
necessaryfor preventionof developmentofinfectiousdiseasesinthese patients.Coatingthe
walls,windows,and doors by CNTs can provide this isolatedroom for this purpose. Present
authors have reported a new antimicrobial PVC nanocomposite comprisingof MWCNTs.The
synthesizednanocomposite hasa strong antimicrobial activity against some bacterial strains.
These researchershave suggested that this newinventioncan be usedas a coating for different
surfaces such as window,wall etc.,especiallyforisolationroomin pediatric section.

18. Nanotechnology in biomedicine
nanotechnology have prompted rapid progress in drug delivery and targeted drug
therapies. The Nano drug delivery systems includes nanoparticles, micelles, liposomes,
colloidal dispersions, polymer drug conjugates and many more. Liposomes are one of the
most versatile components for selective drug and gene delivery. Several liposomes based
formulations has been clinically approved and several undertrials for specific drug deploy
for the treatment of a variety of cancers . The first FDA approved nanomedicine for cancer
treatment; which consisted of doxorubicin (DOX) loaded in a liposomal construct (DOXIL)
for the treatment of Kaposi sarcoma, ovarian cancer, and multiple myeloma. Dendrimeric
structural moieties where the drugs binds covalently tothe dendrimeric sites also
allowing controlled drug release, and thereby making them very effective drug delivery
carriers . Metal (for example Au and Ag as well as metal oxide nanoparticles have also
shown to be the potential candidate as targeted drug delivery vehicles, fluorescent bio-
imaging agents, and also in therapeutictreatment of variety of cancers with minimum
collateral damage to healthy tissues/cells. Several current bio-imaging techniques such as
fluorescence imaging, Raman imaging, computated tomography (CT), positron-emission
tomography (PET), magnetic resonance imaging (MRI), Ultrasound have been used for
monitoring effective drug delivery as well as for early diagnosis. The first magnetic
nanoparticle tested in molecular imaging were super paramagnetic iron oxide
nanoparticles, used as a contrast agent in MRI . Fluorescent nanoparticles, with intrinsic
fluorescence or loaded with fluorescent dyes such as porphyrinoids have also been
explored as imaging agents. A high fluorescence quantum efficacy and photostability is
the key towards the good contrast agent. Several organicmaterials based fluorescent
agents are under investigation to be used as potential contrast agents for different
imaging techniques.nanomaterials for medical applications has been carried out in the
last 30 years; most studies focused on their safety and toxicity on human cell and tissue
function. However, there is a lack of consensus about the influences of particle size,
morphology, surface charge on theirinteractions with tissues, uptake by immune system
cells, and correlations with toxicity orsafety risks. Several critical issues involve the ability
to translate inorganicnanoparticle from academic studies to industrial scaling processes
that comply with commercialquality systems, governmental standards, and regulatory
contexts for human use. In particular, inorganic nanoparticle size and shape, their
physicochemical properties and, most importantly, surface and interfacial properties in
biological systems that result in formation of protein corona on particle surfaces are
critical parameters to consider . In vitro tests may therefore provide only a partial
indication of possible toxicity potential, compared to in vivo exposures. The size of
nanoparticles can determine their half‐life and distribution: while particles <10 nm are
filtered by the kidney, those > 200 nm are phagocytosed and removed by the spleen .
Most therapeutic nanoparticles range from 10 to 100 nm, therefore, they can flow
throughout the circulatory system and penetrate in target tissues through capillaries.
Applications of nanomaterials in medicine involve diagnosticand therapeutic processes
for several diseases affecting different organs.Safe‐by‐design delivery of drugs by means

19. of nanosized carriers may significantly impact drug development and treatment .
Nanosized reporter probes may be employed todeliver and monitor drugs and provide
immediate feedback on the therapeutic effectiveness of the active ingredient.
Novel Therapeutics and Drug Delivery Systems
Nanosizeddrug deliverysystemshave already enteredroutine clinical use and Europe has been
pioneeringinthis field.The most pressingchallenge isapplicationof nanotechnologyto designof
multifunctional,structured materialsable to target specificdiseasesor containingfunctionalities
to allow transport across biological barriers. In addition,nanostructured scaffoldsare urgently
neededfortissue engineering,stimuli-sensitivedevicesfordrugdeliveryand tissue engineering,
and physicallytargeted treatmentsfor local administration oftherapeutics(e.g.via the lung, eye
or skin). To realise the desiredclinical benefitsrapidly, the importance of focusingthe designof
technologiesonspecifictarget diseases was stressed:cancer, neurodegenerativeand
cardiovascular diseaseswere identifiedasthe first priority areas. Longer term prioritiesinclude
the designof synthetic,bioresponsive systemsforintracellular deliveryofmacromolecular
therapeutics(syntheticvectors for gene therapy),and bioresponsive orselfregulateddelivery
systemsincludingsmart nanostructuressuch as biosensorsthat are coupledto the therapeutic
deliverysystems.
Clinical Applications and Regulatory Issues
As the technologies are designed based on a clear understanding of a particulardisease,
diseasespecific oriented focus is required for the development of novel pharmaceuticals.
In addition, it will be important to establish a case-by-case approach to clinical and
regulatory evaluation of each nanopharmaceutical. High priority should be given to
enhancing communication and exchange of information among academia, industry and
regulatory agencies encompassing all facets of this multidisciplinary approach.
The Importance of Nanotechnology in Biomedical Sciences
Patientstoday are seekingbetterhealthcare, while healthcare providersand insurance companies
are calling for cost-effective diagnosisandtreatments.The biomedical industrythus faces the
challenge ofdevelopingdevicesandmaterialsthat offerbenefitstoboth patients and the
healthcare industry. The combinationof biologyand nanotechnology,is expectedtorevolutionize
biomedical researchby exploitingnovel phenomenaandproperties(physical chemical and
biological) ofmaterial presentat nanometer length(10-9m) scale and systemsthrough control of
matter on the nm scale and the directapplication of nanomaterialsto biological targets.Today,
nanomaterialshave beendesignedfora varietyof biomedical and biotechnological applications,
includingbiosensors,enzyme encapsulation;neuronal nanotechnologyisbasedon the
introductionof novel nano-materialswhich can result in revolutionarynewstructures and devices
usingextremelybiological sophisticatedtoolsto preciselypositionmolecules.Carbonnanotubes
(CNT) and functionalizedfullerenesBuckyballs withbio-recognitionpropertiesprovide toolsat a
scale,which offersa tremendousopportunityto study biochemical processesand to manipulate
livingcellsat the single molecule level.Manynanomaterialshave novel chemical and biological
propertiesand most of them are not naturally occurring. Carbon nanotubes have won enormous
popularity innanotechnologyfor their unique propertiesand applications.CNTs have highly
desirable physicochemical propertiesforuse in commercial,environmental and medical sectors.

20. Inclusionof CNTs to improve the qualityand performance of many widelyusedproducts, as well
as potentiallyin medicine,will dramaticallyaffectoccupational and public exposure toCNT-based
bionanomaterialsin the near future. Evensince the discoveryof carbon nanotubes,researchers
have beenexploringtheirpotential inbio applications.One focal point has beenthe production of
nanoscale biosensors and drug deliverysystemsbasedon carbon nanotubes,which has been
drivenby evidence that biological speciessuchas proteinsand enzymescan be immobilizedeither
in the hollow cavity or on the surface of carbon nanotubes.Nanoparticlesornanoporous particles
functionalizedwithorganic groups can be usedas biomarkers,tracer, and drug deliverysystems
with evenall-in-one functionalities forthe treatmentof cancer . Tumor cellscan be imagedin-vivo
or in-vitroby magneticresonance imaging (MRI) using nanoparticlesas contrasting agents.Many
other supports such as of nanoporous sol-gel glasses bioencapsulatedwithproteinscan be used
to mimic and to study folding/unfoldingprocessin-vitrobutalso to trace and detect the
interactionsof encapsulatednanoparticlesemployedas biomarkers.This is a challengingtask that
we are trying to overcome with fluorinatednanoparticlesat fluorotronics withthe development
and utilizationof the new patentedand emergingtechnique knownas Carbon-Fluorin
Spectroscopy.Therefore,there isthenan important issue ofusing nanotechnologyto findnew
therapeuticsbut also as a way for theranostics and nanomedicine.
Nanoparticles in biomedical applications
Nanoparticles are defined as solid colloidal particles ranging in size from 10 to 1000 nm.
Nanoparticles offer many benefits to largerparticles such as increased surface-to-volume
ratio and increased magnetic properties. Over the last few years, there has been a steadily
growing interest in using nanoparticles in different biomedicalapplications such as
targeted drug delivery, hyperthermia, photoablation therapy, bioimaging and biosensors.
Iron oxide nanoparticles have dominated applications, such as drug delivery,
hyperthermia, bioimaging, cell labelling and gene delivery, because of their excellent
properties such as chemical stability, non-toxicity, biocompatibility, high saturation
magnetisation and high magnetic susceptibility. In this review, nanoparticles will be
classified into four different nanosystems metallic nanoparticles, bimetallic or alloy

21. nanoparticles, metal oxide nanoparticles and magnetic nanoparticles. This review
investigates the use of nanosystems other than iron oxide nanoparticles such as metallic
nanoparticles like gold (Au) and silver (Ag), bimetallic nanoparticles like iron cobalt (Fe-Co)
and iron platinum (Fe-Pt) and metal oxides including titanium dioxide (TiO2) cerium
dioxide (CeO2), silica (SiO2) and zinc oxide (ZnO) with a focus on the lesser studied
nanoparticles such as silver (Ag), iron-platinum (Fe-Pt) and titanium dioxide (TiO2) and
how their unique properties allow for their potential use in various biomedical
applications.
Nanoparticles are defined as ‘solid colloidal particles ranging in size from 10 to 1000 nm (1
μm)’ . Nanoparticles are used in biomedical applications as they offer many advantages to
larger particles such as increased surface to volume ratio and increased magnetic
properties . Nanoparticles may be classified into different nanosystems. For the purpose
of this review, nanoparticles will be divided into four nanosystems; metallic nanoparticles,
bimetallic or alloy nanoparticles, metal oxide nanoparticles and magnetic nanoparticles.
Classificationof nanosystems
we will classify nanoparticles into different nanosystems. For the purpose of this review,
nanoparticles will be classified into four different nanosystems metallic nanoparticles,
bimetallic or alloy nanoparticles, metal oxide nanoparticles and magnetic nanoparticles as

22. shown in figure . Please see Appendix 1 for further information on the cell lines
mentioned during this review of the different nanosystems, as shown in Figure, used in
biomedical applications. Some of the bimetallic, metal oxide and magnetic nanoparticles
such as Fe–Pt, Cu–Ni and Fe3O4 may overlap. The list of metallic nanoparticles includes
gold and silver. The bimetallic list includes Fe–Co, Fe–Ni, Fe–Cu, Cu–Ni and Fe–Pt
nanoparticles. The metal oxide nanoparticles consist of TiO2, CeO2, SiO2 and ZnO.
Magnetic nanoparticles are comprised of Fe3O4, Co–Fe2O4 and Mn–Fe2O4. These
nanoparticles are the most investigated as they all possess unique properties that are
essential for use in different biomedical applications such as targeted drug delivery,
magnetic hyperthermia, contrast agents for bioimaging, photoablation therapy and
biosensors.
Targeted drug delivery
Chemotherapy depends on the circulatory system to transport anticancer drugs to the
tumour. There are negative side effects of this treatment such as non-specificity and
toxicity of the drug, whereby the drugs attack healthy cells and organs as well as the
cancerous cells. Therefore, targeted drug delivery is being developed as one alternative to
chemotherapy treatment. The aim of targeted drug delivery is to direct the drug to the
specific area where the tumour is located and thereby increasing the amount of drug
delivered at the tumour site and reducing the side effects. In targeted drug delivery,
magnetic nanoparticles are used to deliver the drug to its specific location. Generally, the
magnetic nanoparticles are coated with a biocompatible layer, such as gold or polymers,
this is done to functionalise the nanoparticles so that the anticancer drug can either be
conjugated to the surface or encapsulated in the nanoparticle as shown in Figure . Once
the drug/nanoparticle complex is administered, an external magnetic field is used to guide
the complex to the specific tumour site. The drug is released by enzyme activity or by
changes in pH, temperature or osmolality.
Magnetic hyperthermia

23. Hyperthermia is a therapeutic technique whereby heat is applied to destroy cancerous
cells and tissue. The temperature of the infected or diseased area is raised to 41–46 °C to
kill the cancerous cells without damaging the healthy cells. Cancerous cells have a higher
sensitivity to temperature than healthy cells. Cell apoptosis will occur when the cancerous
cells are heated to 41–46 °C, this is called hyperthermic effect. Necrosis will occur if the
cells are heated to above 46–48 °C, referred to as thermoablation. Hyperthermia
treatment is used in combination with radiotherapy and chemotherapy to treat cancerous
cells. There are three different types of hyperthermia treatment local, regional and whole
body hyperthermia. In local hyperthermia treatment, heat is applied to a small area which
can be done using different techniques such as radio frequency, microwave and
ultrasound. These methods are used to supply energy toraise the temperature of the
tumour. Magnetic nanoparticles can also be used in local hyperthermia treatment.
Regional hyperthermiais generally used to treat large tissue areas. In this treatment,
external devices are used to heat an organ or limb. Whole body hyperthermia is often
used to treat metastatic cancer that has spreads throughout the body. Local hyperthermia
treatment is the main type of hyperthermia that will be discussed here. For local
hyperthermia treatment, magnetic nanoparticles can be delivered to the tumour in four
possible ways arterial injection, direct injection, in situ implant formation and active
targeting. Arterial injection requires injecting the fluid containing the magnetic
nanoparticles into the tumours arterial supply. Direct injection involves directly injecting
the fluid containing the magneticparticles into the tumourthis method is the most
commonly used. In situ implant formation entails using injectable formulations that form
gels such as hydrogels (chitosan and sodium alginate) and organogels (Poly (ethylene-co-
vinyl alcohol and cellulose acetate) to entrap magnetic particles into tumours.
Active targeting is another method of delivering magnetic nanoparticles to the tumour
site. It generally involves coating the magnetic nanoparticles with a tumour-specific
antibody and injecting into the bloodstream. The antibodies are tumour specificand will
bind to the target site.
Magnetic fluid hyperthermia is based on the principle of converting electromagnetic
energy into heat. The magnetic nanoparticles are distributed around the target site and an
alternating magneticfield is applied. This alternating magnetic field supplies energy which
helps the magnetic moments in the particles to overcome the reorientation energy
barrier. Energy is dissipated when the moments in the particles relax to an equilibrium
state. This then results in the heating of the particles by Brownian rotation or Neél
relaxation .
Bioimaging
There are different bioimaging techniques such as MRI, computed tomography (CT),
positron emission tomography (PET) and ultrasound that are used for the detection and
diagnosis of diseases. These techniques are non-invasive and some can produce high-
resolution images of internal organs. Contrast agents are generally used in these

24. bioimaging techniques in order to identify the organ or tissue of interest as well as
identifying healthy tissue from diseased tissue. The main issue with the current
contrasting agents in use for MRI and CT imaging is the toxicity, low retention time and
low imaging time. In order to improve the imaging time and increase the biocompatibility
of contrast agents, different compounds such as core–shell nanoparticles have been
investigated as possible contrasting agents as they can offer an increased biocompatibility
and imaging time.
Photoablation therapy: photodynamic and
photothermal therapy
Photoablation therapy is classified into photodynamic therapy (PDT) and photothermal
therapy. PDT uses non-toxic light sensitive compounds called photosensitisers and upon
exposure to light, at a certain wavelength, these compounds become toxic. This therapy is
mainly used to target diseased cells such as cancer. In the PDT process once the
photosensitisers, such as TiO2 nanoparticles, are exposed to light at a specific wavelength,
photo-induced electrons and holes are created. The photo-induced electrons and holes
can further react with hydroxyl ions or water and can form oxidative radicals in the form
of reactive oxygen species (ROS) and singlet oxygen. The production of these species leads
to inevitable cell death. Photothermal therapy uses a near infrared (NIR) light source to
irradiate tumour cells. This light energy can be converted to heat energy which can cause
hyperthermia to occur resulting in cell death. TiO2 has many attractive properties such as
biocompatibility, chemical stability and photocatalytic activity. It is these properties
especially its photocatalytic activity that make it an attractive species for use in
photothermal therapy.

25. Figure shows a schematic of the photocatalytic process for TiO2. The photocatalytic
process for TiO2 has three steps excitation, diffusion and surface transfer. In the first step,
the nanoparticles absorb photons from a light source. This energy is enough to overcome
the band gap and promote the electron into the conduction band. This leaves vacancies or
holes in the valance band. The holes and electrons then diffuse to the surface of the
photocatalyst. The last step in this photocatalytic reaction is the production of chemical
reactions on the surface. The creation of holes and electrons results in these reactions.
The holes can react with absorbed surface water and produce hydroxyl radicals, while the
electrons combine with oxygen toform superoxide radical. Figure 4 depicts the
photocatalytic reaction of TiO2.
Biosensors
A biosensor is an analytical device that is used for analysing biological samples. It converts
a chemical, biological or biochemical response into an electrical signal. A biosensor
contains three essential components (1) bioelement or bioreceptor, which are generally
made up of enzymes, nucleic acids, antibodies, cells or tissues (2) the transducer which
can be electrochemical, optical, electronic, piezoelectric, pyroelectric or gravimetric and
(3) the electronic unit which contains the amplifier, processor and display. Figure 5 shows
a schematic of these components. The bioreceptorrecognises the target
analyte/substrate of interest, the transducer then transforms the resulting signal into an
electrical signal that is more easily quantified. Nanoparticles can be used as bioreceptors
once coated with a bioresponsive shell. Biosensors are utilised in many different areas
including environmental, bio/pharmaceutical, food and medical industries.

26. Figure shows a typical schematic of a biosensor. As mentioned previously a typical
biosensor is composed of three main parts the electronic system, which contains the
signal amplifier, processor and display unit, the transducer, which converts the reaction of
the sample analyte and bioreceptorinto an electrical signal and a bioreceptor, which is
composed of a biological substance which targets and or binds to a specific compound.
The transducer used in the biosensor depends on the reaction that is generated between
the sample and the bioreceptor. Electrochemical biosensors such as amperometric sensors
detect changes in current due to oxidation/reduction reactions. Potentiometricsensors
can detect changes in charge distribution. Optical biosensors can be colorimetric which
detect changes in light adsorption or photometric which detect changes in photon output.
Piezoelectric sensors can detect changes in mass.
Disadvantages of Nanotechnology
Beside of mentioned advantages of nanotechnology in biomedicicne, especially in cance
therapy, there are some adverse side effects that limit the widespread use of
nanostructures. According to our previous study, overuse of nanomaterials has led to an
ever growing exposure of living organisms to these substances. Iron oxide nanoparticles
can augment rate of cell death through oxidative stress and lipid peroxidation. Exposure
to zinc oxide, gold and silver nanoparticles can result in cell death via mitochondrial
dysfunction, expression of abnormal protein in cells, andaltering the patterns of gene
expression, respectively. Likewise, carbon nanotubes can lead to an increased rate of cell
death through the reduction of membrane fluidity, thereby destroying cell membrane. All
of used nanostructurs have known and unknown toxicity on all living organism.
Conclusion
In this chapter, the investigation reports on application of nanotechnology in biomedicine
nanostructures in nanotechnology are systematically presented. According tothis chapter,
nanotechnology has potent and benefit application in medicine and this application leads
to the appearance of a new field known as nanomedicine. Nanomadicine can use for
disease treatment especially for cancer disease. The nanostructures including

27. nanopaerticles, nano rods, carbon nanotubes, liposomes and etc. have great potential for
possibly replacing current active agents that used for treatment of cancer. These agents
can also use in cancer- related diseases such as infectious diseases. So, nanotechnology
has opened new cranes on medical research especially on research about new approach
for cancer treatment. However, the adverse side effects of nanostructures have been
limited the widespread use of nanostructures and more investigation in this field is
required.
Acknowledgements
The authors gratefully acknowledge SaritaMaurya ,university of Allahabad , centre of
Bioinformatics and Subhashiashish Dwivedi, I. E.T. for support to conduct this review
work.
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