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Nanotechnology and Cancer TreatmentOm Pal Singh and R. M. NehruAtomic Energy Regulatory BoardNiyamak Bhavan, Anushakti NagarMumbai - 400 049, India

Abstracts : Cancer is caused by damage of genes which control the growth and division ofcells. Detection/diagnose/treatment is possible by confirming the growth of the cells and treatedby rectifying the damaging mechanism of the genes or by stopping the blood supply to thecells or by destroying it. Conventional detection of the cancer is done by observing the physicalgrowth/changes in the organ by X-rays and/or CT Scans and is confirmed by biopsy throughcell culture. However, the limitation of these methods is that these are not very sensitive andthe detection is possible only after substantial growth of the cancerous cells. Nano Particles(NP) being of a few of nano meters size and the cells being of the size of few microns, NP canenter inside the cells and can access the DNA molecules/Genes and therefore, there is apossibility that the defect in the genes can be detected. The conventional treatment options ofcancer are surgery, radiation therapy and chemo therapy. However, all the these methods havetheir own limitations (in surgery one loses the organ and the cancer may appear again, inradiation therapy even the healthy cells get burnt, cancerous cells burning is not uniform andthe burnt part may become dead and non functional, in chemotherapy treatment is harmful tohealthy cells, approach is gross and rarely successful if the cancer is in advanced stage). Inthe nanotechnology methods, certain NP can be designed to absorb preferentially certain wavelength of radiation and if they enters in the cancerous cells, they will burn them. Nanotechnologycan be used to create therapeutic agents that target specific cells and deliver toxin to kill them.The NP will circulate through the body, detect cancer associated molecular changes, assistwith imaging, release a therapeutic agent and then monitor the effectiveness of the intervention.In this paper, the details of these possible detection/ diagnose/ treatment methods ofnanotechnology are presented. In addition the toxic effects of NP and their regulatory aspectsare also discussed.Key word : Cancer, Nanotechnology, Cantilevers, Nanopores, Nanoshells, Quantum Dotes,Health and Environmental Effects, Nanotechnology and Toxicity, Nanotechnology andRegulatory Aspects.

Asian J. Exp. Sci., Vol. 22, No. 2, 2008, 45-50

IntroductionThe theme of nanotechnology is the

control of material on a scale of 1 to 100nanometers and fabricates the devices on thisscale of length. On nano scale, there is vastlyincrease in ratio of surface area to volume.Due to this, materials at nano scale showvery different properties compared to whatthey exhibit on a micro scale, enabling uniqueapplications. For instance,• opaque substances become transparent

(copper),

• inert material becomes catalysts(platinum),

• stable material turn combustible(aluminium),

• solids turns into liquids at roomtemperature (gold),

• insulator become conductors (silicon).A material such as gold which is inert

can become potent chemical catalyst at nanoscale. Some of the unique applications ofnano materials include,

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• titanium dioxide nanoparticles insunscreen,

• cosmetics and some food products,• silver nanoparticles in food packing,

clothing, disinfectants and house-holdappliances.

• zinc oxide nanoparticles in cosmetics,surface coatings, paints and outdoorfurniture varnishes.However, further applications require

actual manipulations or arrangement ofnanoscale components await furtherresearch.

Cancer : Cancer is caused by damageof genes which control the growth anddivision of cells. Genes carry the instructionsfor basic functions of cells. Cancerous cellneed blood supply to grow. A hormone likemolecule causes nearby blood vessel to growtowards the cell to supply the oxygen andother nutrients. Cancer can be cured byrectifying the damaging mechanism of thegenes or by stopping the blood supply to thecells or by destroying it. Detection/diagnoseis possible by confirming the growth of thecells.

One nanometer (nm) is one billionth,or 10–9 of a meter. For comparison, typicalcarbon-carbon bond lengths, or the spacingbetween these atoms in a molecule, are in therange 0.12 - 0.15 nm, and a DNA double-helix has a diameter around 2 nm. On theother hand, the smallest cellular life forms, thebacteria of the genus Mycoplasma, arearound 200 nm in length. Many of the cellsare of the dimensions of micro meter. Thisprovides the possibility of nanoparticlesentering the cells and detect/treat themolecular changes that occur due tocancerous causes, in small percentage of

cells. Therefore, the necessary tools must beextremely sensitive. Scientists andresearchers hope that nanotechnology can beused to create therapectic agents that targetspecific cells and deliver the toxin in acontrolled, time-release manner. The basicaim is to create single agents that are able toboth detect cancer and deliver treatment.The nanoparticles will circulate through thebody, detect cancer-associated molecularchanges, assist with imaging release atherapeutic agent and then monitor theeffectiveness of the intervention.

Cancer DetectionConventional : Conventional detection

of the cancer is done by observing thephysical growth/changes in the organ by X-rays and/or CT Scans and is confirmed bybiopsy through cell culture. However thelimitation of this method is that it is not verysensitive and the detection is possible onlyafter substantial growth of the cancerouscells. Often the treatment is also not possibleonce the cancer is in such an advanced stage.

Nano Technology Detection : Asmentioned before, nanoparticles (NP) are ofa few of nm and the cells are of the size offew microns. So NP can enter inside the cellsand can access the DNA molecules/Genesand, there is a possibility that the defect inthe genes can be detected. DNA moleculescan be detected in their incipient stage. Thiscould be possible in vivo or in vitro. It willbe shown latter that NP do show potentialof cancer detection in its incipient stage.

Cancer TreatmentConventional : One of the treatment

option is surgery. That is, remove thecancerous part. However, the limitation isthat one loses the organ and the cancer mayappear again. Further, the surgery is not

Singh O.P. and Nehru R.M. (2008) Asian J. Exp. Sci., 22(2), 45-50

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possible for all types of cases of the cancer.Second option is radiation therapy. In this thecancerous cells are burnt by radiation ofspecific frequency band and the intensity. Thelimitation of this method is that even thehealthy cells get burnt, cancerous cellsburning is not uniform and the burnt part maybecome dead and non functional. The thirdoption is chemotherapy. That is, cancerouscells are killed by drugs toxic to cells or bystopping cells from taking nutrients neededto divide the cells or stop the mechanismresponsible for division of the cell. Normallya combination of drugs is given so that drugsaffect all the three aspects of the cancertreatment. The limitation of this approach isthat treatment is harmful to healthy cells,approach is gross and rarely successful if thecancer is in advanced stage.

Nanotechnology : Certain nanoparticles can be designed to absorbpreferentially certain wave length of radiationand gets heated. Such a NP if enters in the

cancerous cell will burn it if irradiated bysuitable wavelength radiation. This is kind ofthe analogue of radiation therapy. Asmentioned before, nanotechnology can beused to create therapeutic agents that targetspecific cells and deliver toxin to kill them.The NP will circulate through the body, detectcancer associated molecular changes, assistwith imaging release a therapeutic agent andthen monitor the effectiveness of theintervention.

Tools of NanotechnologySome of the tools of nanotechnology

having applications in cancer detection andtreatment are the following :

(i) Cantilevers : Tiny bars anchoredat one end can be engineered to bind tomolecules associated with cancer. Thesemolecules may bind to altered DNA proteinsthat are present in certain types of cancer(Fig.1). This will change the surface tensionand cause the cantilevers to bend. By

Fig.1 : Schematic diagram showing Cantilevers (Source: National Cancer Institute, USA)

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monitoring the bending of cantilevers, itwould be possible to tell whether the cancermolecules are present and hence detect earlymolecular events in the development ofcancer.

(ii) Nanopores : Nanopores (holes)allow DNA to pass through one strand at atime and hence DNA sequencing can bemade more efficient. Thus the shape andelectrical properties of each base on thestrand can be monitored. As these propertiesare unique for each of the four bases thatmake up the genetic code, the passage ofDNA through a nanopore can be used todecipher the encoded information, includingerrors in the code known to be associatedwith cancer.

(iii) Nanotubes : Nanotubes aresmaller than Nano pores. Nanotubes &carbon rods, about half the diameter of amolecule of DNA, will also help identifyDNA changes associated with cancer (Fig.2). It helps to exactly pin point location ofthe changes. Mutated regions associatedwith cancer are first tagged with bulkymolecules. Using a nano tube tip, resemblingthe needle on a record player, the physicalshape of the DNA can be traced. A computer

translates this information into topographicalmap. The bulky molecules identify the regionson the map where mutations are present.Since the location of mutations can influencethe effects they have on a cell, thesetechniques will be important in predictingdisease.

(iv) Quantum Dotes (QD) : Theseare tiny crystals that glow when these arestimulated by ultraviolet light. The latexbeads filled with these crystals whenstimulated by light, the colors they emit actas dyes that light up the sequence of interest.By combining different sized quantum doteswithin a single bead, probes can be createdthat release a distinct spectrum of variouscolors and intensities of lights, serving as sortof spectral bar code.

(v) Nanoshells (NS) : These areanother recent invention. NS are minisculebeads coated with gold. By manipulating thethickness of the layers making up the NS, thebeads can be designed that absorb specificwavelength of light. The most usefulnanoshells are those that absorb near-infrared light that can easily penetrate severalcentimeters in human tissues. Absorption oflight by nanoshells creates an intense heat thatis lethal to cells. Nanoshells can be linked toantibodies that recognize cancer cells. Inlaboratory cultures, the heat generated by thelight-absorbing nanoshells has successfullykilled tumor cells while leaving neighbouringcells intact.

(vi) Dendrimer : A number ofnanoparticles that will facilitate drug deliveryare being developed. One such molecule thathas potential to link treatment with detectionand diagnostic is known as dendrimer. Thesehave branching shape which gives them vastamounts of surface area to which therapeuticagents or other biologically active moleculescan be attached. A single dendrimer can carry

Fig. 2 : Schematic diagram showingNanotubes (Source: National Cancer Institute,

USA)

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a molecule that recognizes cancer cells, atherapeutic agent to kill those cells and amolecule that recognizes the signals of celldeath. It is hoped that dendrimers can bemanipulated to release their contents only inthe presence of certain trigger moleculesassociated with cancer. Following drugreleases, the dendrimers may also reportback whether they are successfully killingtheir targets.

The technologies mentioned above arein the various stages of discovery anddevelopment. Some of the technologies likequantum dots, nano pores and other devicesmay be available for detection and diagnosisand for clinical use within next ten years.

Challenges of TechnologyToday, much of the science on the

nanoscale is basic research, designed toreach a better understanding of how matterbehaves on this small scale. The surface areaof nano-materials being large, the phenomenalike friction and sticking are more importantthen they are in large systems. These factorswill affect the use of nanomaterials bothinside and outside the body. Nanostructuresbeing so small; the body may clear them toorapidly to be effective in detection or imaging.Larger nanoparticles may accumulate in vitalorgans, creating a toxicity problem.

Some Important DevelopmentsCarbon Nano Tubes (CNT) have anovel and useful properties and theirmanufacturing will increase. The availableknowledge indicates that CNT may haveunusual toxicity properties.Chitosom nanoparticles withenccapslated quantum dots have beensynthesized and used to deliver of HERZSiRNA. Using such a construct, thedelivery and transfection of the SiRNAcan be monitored by the presence of

fluorescent QDs in the Chitosan NPs.Targeted delivery of HERZ SiRNA toHER2 – over expressing SKBR3 breastcancer cells has been shown to bespecific with chetosen/QD NP surfacelabled with HERz antibody targeting theHERz receptors on SkBR3 cells. Genesilencing effects of the conjugatedSiRNA has also been established usingthe luciferase and HER2ELISA assays.These self tracking SiRNA delivery NPwill aid in the monitoring of future genesilencing studies in vivo.By the use of quantum dots which arepowerful tools used for simultaneousimaging of multiple proteins, the minutedifferences in the subcellular niche ofthese two proteins in normal and cancercells has been visualized.

Health and Environmental EffectsThere is a growing body of scientific

evidence which demonstrates the potentialfor some nanomaterials to be toxic to humansor the environment. The smaller a particle,the greater its surface area to volume ratioand the higher its chemical reactivity andbiological activity. The greater chemicalreactivity of nanomaterials results in increasedproduction of reactive oxygen species(ROS), including free radicals. ROSproduction has been found in a diverse rangeof nanomaterials including carbon fullerenes,carbon nanotubes and nanoparticle metaloxides. ROS and free radical production isone of the primary mechanisms ofnanoparticle toxicity; it may result in oxidativestress, inflammation, and consequent damageto proteins, membranes and DNA. Theextremely small size of nanomaterials alsomeans that they are much more readily takenup by the human body than larger sizedparticles. Nanomaterials are able to crossbiological membranes and access cells,

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tissues and organs that larger-sized particlesnormally cannot. Nanomaterials can gainaccess to the blood stream followinginhalation or ingestion. At least somenanomaterials can penetrate the skin; evenlarger microparticles may penetrate skinwhen it is flexed. Broken skin is an ineffectiveparticle barrier, suggesting that acne, eczema,shaving wounds or severe sunburn mayenable skin uptake of nanomaterials morereadily. Once in the blood stream,nanomaterials can be transported around thebody and are taken up by organs and tissuesincluding the brain, heart, liver, kidneys,spleen, bone marrow and nervous system.Studies demonstrate the potential fornanomaterials to cause DNA mutation andinduce major structural damage tomitochondria, even resulting in cell death.

Size is therefore a key factor indetermining the potential toxicity of a particle.However it is not the only important factor.Other properties of nanomaterials thatinfluence toxicity include: chemicalcomposition, shape, surface structure,surface charge, aggregation and solubility,and the presence or absence of functionalgroups of other chemicals. The large numberof variables influencing toxicity means that itis difficult to generalise about health risksassociated with exposure to nanomaterials –each new nanomaterial must be assessedindividually and all material properties mustbe taken into account.

Regulatory AspectsIn a report of seminar in 2004,

Nanoscience and naotechnologies:Opportunities and Uncertaintities, the UnitedKingdom’s Royal Society recommended thatnanomaterials be regulated as new chemicals.Research laboratories and factories shouldtreat nanomaterials “as if they were

hazardous“. That release of nanomaterialsinto the environment be avoided as far aspossible, and that products containingnanomaterials be subject to new safety testingrequirements prior to their commercialrelease. Yet regulations world-wide still failto distinguish between materials in theirnanoscale and bulk form.This means thatnanomaterials remain effectively unregulated.There is no regulatory requirement fornanomaterials to face new health and safetytesting or environmental impact assessmentprior to their use in commercial products, ifthese materials have already been approvedin bulk form.

Summary• Nanotechnology has large potential in

detection and treatment of cancer in itsincipient stage.

• The potential arises due to the ability ofNP entering inside the cells and accessto the chromosomes/FNA molecules.

• Certain nano structures likenanocantilevers, nanopores, nanotubes,nanoshells and quantum dotes areprospective structures that would help indetecting and treatment of cancers.

• Dendrimers are to serve detection,treatment and signaling that the cells arekilled.

• Still there are many challenges that areto be met before use of NT becomes areality.

• Toxicity of the NP is an issue that is tobe resolved through legislative andregulatory means.

Acknowledgement :The paper has been prepared based on

the information available on the internet.

Singh O.P. and Nehru R.M. (2008) Asian J. Exp. Sci., 22(2), 45-50