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NANOTECHNOLOGY CRITICAL ENDEAVOR IN CANCER

1.0 ABSTRACT The advent of nanotechnology in cancer research co ldn!t have co"e at a "ore o##ort ne ti"e$ The vast %no&ledge of cancer geno"ics and #roteo"ics e"erging as a res lt of the H "an Geno"e 'ro(ect is #roviding critically i"#ortant details of ho& cancer develo#s) &hich) in t rn) creates ne& o##ort nities to attac% the "olec lar nder#innings of cancer$ Ho&ever) scientists lac% the technological innovations to t rn #ro"ising "olec lar discoveries into *enefits for cancer #atients$ It is here that nanotechnology can #lay a #ivotal role) #roviding the technological #o&er and tools that &ill ena*le those develo#ing ne& diagnostics) thera#e tics) and #reventives to %ee# #ace &ith today!s e+#losion in %no&ledge$ Nanotechnology #rovides the si,ed "aterials that can *e synthesi,ed and f nction in the sa"e general si,e range and -iologic str ct res$ Atte"#ts are "ade to develo# for"s of anticancer thera#e tics *ased on nano"aterials$ Dendritic #oly"er nanodevices serves as a "eans for the detection of cancer cells) the identification of cancer signat res) and the targeted delivery of anti.cancer thera#e tics /cis.#latin) "ethotre+ate) and ta+ol0 and contrast agents to t "or cells$ Initial st dies doc "ented the synthesis and f nction of a targeting "od le) several dr g delivery co"#onents) and t&o i"aging1contrast agents$ Analytical techni2 es have *een develo#ed and sed to confir" the str ct re of the device$ 'rogress has *een "ade on the s#ecifically triggered release of the thera#e tic agent &ithin a t "or sing high.energy lasers$ The &or% to date has de"onstrated the feasi*ility of the nano.device conce#t in act al cancer cells in vitro$

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2.0 INTRODUCTION Nanotechnology offers the n#recedented and #aradig".changing o##ort nity to st dy and interact &ith nor"al and cancer cells in real ti"e) at the "olec lar and cell lar scales) and d ring the earliest stages of the cancer #rocess$ Thro gh the concerted develo#"ent of nanoscale devices or devices &ith nanoscale "aterials and co"#onents) the NCI Alliance for Nanotechnology in Cancer &ill facilitate their integration &ithin the e+isting cancer research infrastr ct re$ The Alliance &ill *ring ena*ling technologies for3 I"aging agents and diagnostics that &ill allo& clinicians to detect cancer earliest stages 4yste"s that &ill #rovide real.ti"e assess"ents of thera#e tic and s rgical efficacy for accelerating clinical translation 5 ltif nctional) targeted devices ca#a*le of *y#assing *iological *arriers to deliver " lti#le thera#e tic agents directly to cancer cells and those tiss es in the "icroenviron"ent that #lay a critical role in the gro&th and "etastasis of cancer $ Agents that can "onitor #redictive "olec lar changes and #revent #recancero s cells fro" *eco"ing "alignant Novel "ethods to "anage the sy"#to"s of cancer that adversely i"#act 2 ality of life Research tools that &ill ena*le ra#id identification of ne& targets for clinical develo#"ent and #redict dr g resistance$ 3.0 NANOTECHNOLOGY IN CANCER Nanoscale devices are so"e&here fro" one h ndred to ten tho sand ti"es s"aller than h "an cells$ They are si"ilar in si,e to large *iological "olec les /6*io"olec les60 s ch as en,y"es and rece#tors$ As an e+a"#le) he"oglo*in) the "olec le that carries o+ygen in red *lood cells) is a##ro+i"ately 7 nano"eters in dia"eter$ Nanoscale devices s"aller than 78 nano"eters can easily enter "ost cells) &hile those s"aller than 98 nano"eters can "ove o t of *lood vessels as they circ late thro gh the *ody$ -eca se of their s"all si,e) nanoscale devices can readily interact &ith *io"olec les on *oth the s rface of cells and inside of cells$ -y gaining access to so "any areas of the *ody) they have the #otential to detect disease and deliver treat"ent in &ays ni"agined *efore no&$ And since *iological #rocesses) incl ding events that lead to cancer) occ r at the nanoscale at and inside cells) nanotechnology offers a &ealth of tools that are #roviding cancer researchers &ith ne& and innovative &ays to diagnose and treat cancer . 4.0 NANOTECHNOLOGY AND CANCER THERAPY www.Fullinterview.com

www.Fullinterview.com Nanoscale devices have the #otential to radically change cancer thera#y for the *etter and to dra"atically increase the n "*er of highly effective thera#e tic agents$ Nanoscale constr cts can serve as c sto"i,a*le) targeted dr g delivery vehicles ca#a*le of ferrying large doses of che"othera#e tic agents or thera#e tic genes into "alignant cells &hile s#aring healthy cells)greatly red cing or eli"inating the often n#alata*le side effects that acco"#any "any c rrent cancer thera#ies$ On an e2 ally nconventional front) efforts are foc sed on constr cting ro* st :s"art; nanostr ct res that <ill event ally *e ca#a*le of detecting "alignant cells in vivo) #in#ointing their location in the *ody) %illing the cells) and re#orting *ac% that their #ayload has done its (o*$ The o#erative #rinci#les driving these c rrent efforts are "od larity and " ltif nctionality) i$e$) creating f nctional * ilding *loc%s that can *e sna##ed together and "odified to "eet the #artic lar de"ands of a given clinical sit ation$ 5.0 NANOWIRES In this diagra") nano si,ed sensing &ires are laid do&n across a "icrofl idic channel$ These nano&ires *y nat re have incredi*le #ro#erties of selectivity and s#ecificity$ As #articles flo& thro gh the "icrofl idic channel) the nano&ire sensors #ic% # the "olec lar signat res of these #articles and can i""ediately relay this infor"ation thro gh a connection of electrodes to the o tside &orld$ These nanodevices are "an."ade constr cts "ade &ith car*on) silicon and other "aterials that have the ca#a*ility to "onitor the co"#le+ity of *iological #heno"enon and relay the infor"ation) as it is "onitored) to the "edical care #rovider$ They can detect the #resence of altered genes associated &ith cancer and "ay hel# researchers #in#oint the e+act location of those changes

6.0 CANTILEVERS

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www.Fullinterview.com Nanoscale cantilevers = "icrosco#ic) fle+i*le *ea"s rese"*ling a ro& of diving *oards = are * ilt sing se"icond ctor lithogra#hic techni2 es$ These can *e coated &ith "olec les ca#a*le of *inding s#ecific s *strates>DNA co"#le"entary to a s#ecific gene se2 ence) for e+a"#le$ 4 ch "icron.si,ed devices) co"#rising "any nano"eter.si,ed cantilevers) can detect single "olec les of DNA or #rotein$ As a cancer cell secretes its "olec lar #rod cts) the anti*odies coated on the cantilever fingers selectively *ind to these secreted #roteins$ These anti*odies have *een designed to #ic% # one or "ore different) s#ecific "olec lar e+#ressions fro" a cancer cell$ The #hysical #ro#erties of the cantilevers change as a res lt of the *inding event$ Researcherscan read this change in real ti"e and #rovide not only infor"ation a*o t the #resence and the a*sence * t also the concentration of different "olec lar e+#ressions$ Nanoscale cantilevers) constr cted as #art of a larger diagnostic device) can #rovide ra#id and sensitive detection of cancer.related "olec les$

7.0 NANOSHELLS Nanoshells have a core of silica and a "etallic o ter layer$ These nanoshells can *e in(ected safely) as de"onstrated in ani"al "odels$-eca se of their si,e) nanoshells &ill #referentially concentrate in cancer lesion sites$ This #hysical selectivity occ rs thro gh a #heno"enon called enhanced #er"eation retention /E'R0$4cientists can f rther decorate the nanoshells to carry "olec lar con( gates to the antigens that are e+#ressed on the cancer cells the"selves or in the t "or "icroenviron"ent$ This second degree of s#ecificity #referentially lin%s the nanoshells to the t "or and not to neigh*oring healthy cells$ As sho&n in this e+a"#le) scientists can then e+ternally s ##ly energy to these cells$ The s#ecific #ro#erties associated &ith nanoshells allo& for the a*sor#tion of this directed energy) creating an intense heat that selectively %ills the t "or cells$ The e+ternal energy can *e "echanical) radio fre2 ency) o#tical = the thera#e tic action is the sa"e$The res lt is greater www.Fullinterview.com

www.Fullinterview.com efficacy of the thera#e tic treat"ent and a significantly red ced set of side effects$ 8.0 NANOPARTICLES Nanoscale devices have the #otential to radically change cancer thera#y for the *etter and to dra"atically increase the n "*er of highly effective thera#e tic agents$In this e+a"#le) nano#articles are targeted to cancer cells for se in the "olec lar i"aging of a "alignant lesion$ Large n "*ers of nano#articles are safely in(ected into the *ody and #referentially *ind to the cancer cell) defining the anato"ical conto r of the lesion and "a%ing it visi*le$ These nano#articles give s the a*ility to see cells and "olec les that &e other&ise cannot detect thro gh conventional i"aging$ The a*ility to #ic% # &hat ha##ens in the cell > to "onitor thera#e tic intervention and to see &hen a cancer cell is "ortally &o nded or is act ally activated > is critical to the s ccessf l diagnosis and treat"ent of the disease$ Nano#artic late technology can #rove to *e very sef l in cancer thera#y allo&ing for effective and targeted dr g delivery *y overco"ing the "any *iological) *io#hysical and *io"edical *arriers that the *ody stages against a standard intervention s ch as the ad"inistration of dr gs or contrast agents$

9.0 CHALLENGES www.Fullinterview.com

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The si+ "a(or challenge areas of e"#hasis incl de3 9.1 P !"!#$%&# '#( C&#$ &) &* C'#+! , Develo#ing nanoscale devices that can deliver cancer #revention agents Designing " ltico"#onent anticancer vaccines sing nanoscale delivery vehicles 9.2 E' )- D!$!+$%&# '#( P &$!&.%+/, Creating i"#lanta*le) *iofo ling.indifferent "olec lar sensors that can detect cancer.associated *io"ar%ers that can *e collected for e+ vivo analysis or analy,ed in sit ) &ith the res lts *eing trans"itted via &ireless technology to the #hysician Develo#ing :s"art; collection #latfor"s for si" ltaneo s "ass s#ectrosco#ic analysis of " lti#le cancer.associated "ar%ers$ 9.3 I.'0%#0 D%'0#&/$%+/, Designing :s"art; in(ecta*le) targeted contrast agents that i"#rove the resol tion of cancer to the single cell level Engineering nanoscale devices ca#a*le of addressing the *iological and evol tionary diversity of the " lti#le cancer cells that "a%e # a t "or &ithin an individ al$ 9.4 12)$%*2#+$%&#') T3! '4!2$%+/, Develo#ing nanoscale devices that integrate diagnostic and thera#e tic f nctions Creating :s"art; thera#e tic devices that can control the s#atial and te"#oral release of thera#e tic agents &hile "onitoring the effectiveness of these agents 9.5 52')%$- &* L%*! E#3'#+!.!#$ %# C'#+! , Designing nanoscale devices that can o#ti"ally deliver "edications for treating conditions that "ay arise over ti"e &ith chronic anticancer thera#y) incl ding #ain) na sea) loss of a##etite) de#ression) and diffic lty *reathing$ 9.6 I#$! (%/+%4)%#' - T '%#%#0, Coordinating efforts to #rovide cross.training in "olec lar and syste"s *iology to nanotechnology engineers and in nanotechnology to cancer researchers$ Creating ne& interdisci#linary co rse&or%1degree #rogra"s to train a ne& generation of researchers s%illed in *oth cancer *iology and nanotechnology$

10.0 CONCLUSION

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www.Fullinterview.com <or% is c rrently *eing done to find &ays to safely "ove these ne& research tools into clinical #ractice$ Today) cancer.related nanotechnology is #roceeding on t&o "ain fronts3 la*oratory.*ased diagnostics and in vivo diagnostics and thera#e tics$ Nanodevices can #rovide ra#id and sensitive detection of cancer.related "olec les *yena*ling scientists to detect "olec lar changes even &hen they occ r only in a s"all #ercentage of cells$ Nanotechnology is #roviding a critical *ridge *et&een the #hysical sciences and engineering) on the one hand) and "odern "olec lar *iology on the other$ 5aterials scientists) for e+a"#le) are learning the #rinci#les of the nanoscale &orld *y st dying the *ehavior of *io"olec les and *io"olec lar asse"*lies$ In ret rn) engineers are creating a host of nanoscale tools that are re2 ired to develo# the syste"s *iology "odels of "alignancy needed to *etter diagnose) treat) and lti"ately #revent cancer$ In #artic lar) *io"edical nanotechnology is *enefiting fro" the co"*ined efforts of scientists fro" a &ide range of disci#lines) in *oth the #hysical and *iological sciences) &ho together are #rod cing "any different ty#es and si,es of nanoscale devices) each &ith its o&n sef l characteristics$

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