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Gopal Krishan
The Technological Institute of Textile& Sciences,
Bhiwani-127021
[email protected]
C. L. Mittal
ABES Engineering College, Noida
[email protected]
Kapil Singal
The Technological Institute of Textile
& Sciences, Bhiwani-127021
[email protected]
Hitesh
The Technological Institute of Textile
& Sciences, Bhiwani-127021
[email protected]
Carbon Nanotubes &
Nanoparticles in Cancer
TherapyAbstract- The field of nanotubes and nanoparticle is
evolving at a
rapid pace, with many potential applications in electronics,
optics,and sensors, to name a few. This paper reviews the
applications of
Carbon Nanotubes & Nanoparticles in Cancer Therapy.
Carbon
nanotubes are unique nanostructures with remarkable
electronicand mechanical properties. Fullerene research has
blossomed in
many different directions, and has attracted a great deal of
attentionto Carbon Science. We have presented an overview of
various
growth methods for multi-walled and single-walled carbon
nanotubes. Single-walled carbon nano-tubes (SWCNTs) have
beenidentified as a transporter for anticancer drugs.
Keywords: Cancer Therapy, CNT, Microscopy, Tumour, Nano-
particle,
1. INTRODUCTION
With more than 10 million new cases everyyear, cancer is one of
the most devastating diseases[6]. Though the current treatments of
cancer bysurgery, radiation and chemotherapy are successfulin
several cases, these curative methods also killhealthy cells and
cause toxicity to the patient [1], like
bone marrow suppression, gastric erosion, hair loss,renal
toxicity, cardiomyopathy, and several effectson other systems
[2].
It would therefore be desirable to developmethods to directly
target cancerous cells withoutaffecting normal ones [1].
Nanotechnology is beingapplied extensively to provide targeted
drugtherapy, diagnostics, tissue regeneration, cellculture,
biosensors and other tools in the field ofmolecular biology.
Various nanotechnology
platforms like CNT, fullerenes, quantum dotsliposomes,
dendrimers and bucky-balls are beingdeveloped [2].
2. MATERIALS AND METHODS
CNT (Carbon Nano-tubes)
The first carbon nanotube was discovered in1991 by scientist
Sumio Iijima [3], are tubularstructures like a sheet of graphite
rolled into a
cylinder capped at one or both ends by a bucky-ball[2]. A few
years later in 1993, single walledcarbon nanotubes (SWCNT) were
discovered byIijimas group at NEC and Donald Bethune's groupat
IBM's Almaden Research Center in California [3].Carbon nanotubes
(CNTs) are of particular interestin a wide variety of applications
due to their 1Dnature [7], and their versatile mechanical [8], [9],
[10], [11]
and electronic properties [12]. CNTs are analogous toa mono
layered graphite sheet rolled into tubes ofdiameter 1-10 nm, and
hence form hollow tubulesof a single layer of carbon atoms,
rendering themhighly sensitive to changes of their sidewall
surface
properties [13], [4].
The potential use of SWCNTs & MWCNTsis to treat several
types of cancers, with minimal orno toxic effects to normal cells
[1]. Single Walled
Nanotube (SWCNT) has an internal diameter of 1-2nm and multi
walled nanotube has a diameter of 2-25 nm with 0.36 nm distance
between layers ofMWCNT. These vary in their length ranging from 1m
to a few micrometers [14], [2].
As the sidewall of SWCNTs is highly
hydrophobic, they are practically insoluble in water.Therefore,
SWCNTs are functionalized by covalentor non-covalent routes that
will help indisentangling the CNT bundles and make themsoluble in
water. Liu et al. [15] prepared a solution of
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SWCNTs wrapped in poly ethylene glycol (PEG)with a tumour-
targeting cyclic arginineglycineaspartic acid peptide to the end of
the PEG chains.This solution was injected into mice bearingtumours
and it was observed that the targetedSWCNTs accumulated in tumors
[15], [1].
The above finding has prompted studies to
attach a cancer chemotherapy drug doxoyrubicin(DOX) molecule
onto pre-functionalized nanotubes,
possibly for in vivo cancer therapy [16], [1].
FULLERENES
Fullerenes, a carbon allotrope, also called asbucky balls were
discovered in 1985 [17]. TheBuckminster fullerene is the most
common form offullerene measuring about 7 in diameter with 60carbon
atoms arranged in a shape known as
truncated icosahedrons[18]
. It resembles a soccer ballwith 20 hexagons and 12 pentagons
and is highlysymmetrical [19]. Fullerenes are being investigatedfor
drug transport of antiviral drugs, antibiotics andanticancer agents
[2].
Unlike other molecules that haveapplications as cancer drug
delivery vehicles,fullerenes don't break down in the body and
areexcreted intact. This trait can be important for somecancer
treatment compounds that are dangerous to
healthy cells [20].
Fig-1 Fullerenes
QUANTUM DOTS
Quantum dots are Nano crystals measuringaround 2-10 nm which can
be made to fluorescencewhen stimulated by light. It can also be
used forimaging of sentinel node in cancer patients fortumour
staging and planning of therapy [22]. This
method can be adopted for various malignancieslike melanoma,
breast, lung and gastrointestinaltumors [2].
Fig-2 Quantum Dots
LIPOSOMESLiposomes discovered in mid 1960s were
the original models of Nano scaled drug deliverydevices. They
are spherical nanoparticles made oflipid bilayer membranes with an
aqueous interior
but can be uni-lamellar with a single lamella ofmembrane or
multi-lamellar with multiplemembranes. Cancer chemotherapeutic
drugs andother toxic drugs like amphotericin and hamycin,when used
as liposomal drugs produce much betterefficacy and safety as
compared to conventional
preparations. These liposomes can be loaded withdrugs either in
the aqueous compartment or in thelipid membrane [23], [2].
Fig-3 liposomes
During cancer treatment they encapsulatedrugs, shielding healthy
cells from their toxicity,and prevent their concentration in
vulnerable tissuessuch as those of a patient's kidneys and
liver.
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Liposomes can also reduce or eliminate certaincommon side
effects of cancer treatment such asnausea and hair loss [5].
DENDRIMER
This fascinating particle holds significant promise for cancer
treatment. Its many branches
allow other molecules to easily attach to its
surface.Researchers have fashioned dendrimers intosophisticated
anti-cancer machines carrying fivechemical tools- a molecule
designed to bind tocancer cells, a second that fluoresces upon
locatinggenetic mutations, a third to assist in imaging tumorshape
using X-rays, a fourth carrying drugs releasedon demand, and a
fifth that would send a signalwhen cancerous cells are finally
dead. The creatorsof these dendrimers have had successful tests
withcancer cells in culture and plan to try them in living
animals soon [5].
BUCKY-BALLS
Bucky-ball is the common name for amolecule called
Buckminsterfullerene, which ismade of 60 carbon atoms formed in the
shape of ahollow ball. British scientist Harry Krotodiscovered it
in 1985[24], [5].
Bucky-balls may see widespread use in
future products and applications, from drug-deliveryvehicles for
cancer therapy [25] as hollow success-bucky-balls for cancer
treatment [5].
Fig-4 Hollow success bucky-ball
Trapping C60 Bucky-balls in lipid globescould deliver improved
cancer treatments, Atsushi
Ikeda and colleagues from the Nara Institute ofScience and
Technology in Ikoma showed that thecarbon isotope C60 could be
delivered into human
cancer cells by hollow lipid spheres and used toinduce cell
death under visible light irradiation [20].3. Medical effects of
CNT & other Nano-
particles
Development of newer drug deliverysystems based on
nanotechnology methods is being
tried for conditions like cancer, diabetes, fungalinfections,
viral infections and in gene therapy. Themain advantages of this
modality of treatment aretargeting of the drug and enhanced safety
profile.
Nanotechnology has also found its use in diagnosticmedicine as
contrast agents, fluorescent dyes andmagnetic nanoparticles [2]. It
is shown in Table-1.
Table-1 Carbon Nanoparticles Used For Medical
Application
Product Description
Use
AuroLase Gold Nanoshell
Head and neckcancer
INGN 401 Nanoparticleformulationof tumour
suppressiongeneFUS1
Lung cancer
Abraxane albumin boundtaxane
particles
Non-small celllung cancer
Doxil Liposomaldoxorubicin
Ovarian tumour
MRX 952 Nanoparticlepreparation to
encapsulatecamptothecinanalogues
Tumours
Targeted Nano
Therapeutics(TNT)system
TNT with
polymer coatediron oxidemagnetic
particle
Solid tumours
Cyclosert-Camptothecin
IT 101
-Cylcodextrinpolymerdrug deliverysystem
Solid tumours
4. Experimental Detail
In 2004, Sirdeshmukh et al. used CM(Confocal Microscopy) and TEM
(TransmissionElectron Microscopy) with negative staining using
phosphotungstic acid to view fluorescently tagged
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CNTs in monoclonal mouse IgG to cell surfacereceptors in cancer
cells [4].
In 2006, Gong, et al. used Scanning ElectronMicroscopy (SEM) and
Transmission ElectronMicroscopy (TEM) technologies and A
ZeissDSM982 Gemini Field Emission Scanning ElectronMicroscope
(FESEM) with a Schottky electronsource used into the detection of
protein cancer
biomarkers not only in serum but in cellular tissues[29].
In 2009, Heister, et al. used ScanningElectron Microscopy (SEM),
High ResolutionTransmission Electron Microscopy (HR-TEM),Atomic
Force Microscopy (AFM), RamanSpectroscopy, and Thermo-Gravimetric
Analysis(TGA) technologies in order to evaluate the purityand
physical - chemical properties of pristine and
oxidised Nanolab SWCNTs. These allows for theattachment of a
monoclonal antibody for targetingpurposes, an anti-cancer drug, and
a fluorescent dyeat non-competing binding sites to
enablevisualization of cellular uptake and also in thesecond step
of the coupling reaction, the anti-cancerdrug doxorubicin is
non-covalently attached to thesidewalls of oxidized carbon
nanotubes via p-stacking and hydrophilic interactions
withcarboxylic groups [30].
In 2010, Zhu, et al. used Anti-Sense Oligo-Deoxy-Nucleotides
(ASODNs) to investigation inmany different fields such as cancer
therapy,cardiovascular disease, and infectious disease anddevelops
a novel and nontoxic vector based on thefunctionalized carbon
nanotube for cancer therapyand intracellular locations [31].
5. Coat Carbon Nanotubes In Cancer
Treatment
SWCNTs do not only aid in chemotherapytreatment, but in several
other innovative cancertreatments as well as Coat Carbon Nanotubes
withfolate molecules and insert them into the cancer
patients body. The CNTs are coated with folatemolecules because
cancerous cells, unlike healthyones, contain receptors for the
vitamin folate. Thusthe carbon nanotubes will only enter the
malignantcells and not the healthy ones. Because of the
folatemolecules, this process targets and kills only the
cancerous cells within the body, leaving the healthyones
untouched and undamaged [27],[3].
Another treatment for killing cancerous cellsis very similar to
the one discussed in the previous
paragraph. In this case, scientist BalajiPanchapakesan, from the
University of Delaware,
patented a process in which he uses explodingcarbon nanotubes to
kill cancerous cells [28].
6. Research to Futuristic Approach
Over the past few years, breakthroughs have been made pertaining
to the use of carbonnanotubes in the medical field. Many of
theseadvances have been specifically focusing on the useof carbon
nanotubes in cancer research. Scientistshave been trying to find
ways to utilize the amazing
properties of carbon nanotubes to fight cancer andto alleviate
some of the side effects associated withother cancer treatments,
such as chemotherapy [26].
7. At last the ray of light
It might have been found that Single-walledcarbon nanotubes have
been proven safe and stableto use in inserting and transporting
drugs into the
body. Though very small, their properties allowthem to make a
huge impact on the field of science.If advances continue,
single-walled carbonnanotubes may just be the answer to a
brighterfuture for cancer and chemotherapy treatment [3].
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