Carbon nanotubes show promise for cancer treatment through targeted drug delivery and imaging. They can be functionalized with targeting ligands and loaded with anticancer drugs. Nanotubes effectively deliver drugs intracellularly and release their payload within cells. Detection of cancer biomarkers is also improved using carbon nanotube-based electrochemical sensors and immunosensors. Overall, carbon nanotubes represent a nanotechnology platform that can enhance chemotherapy through improved targeting and monitoring of cancer.
2. introducti
on
• Cancer is a group of diseases which involves uncontrollable and abnormal growth
by means of the potential to invade or spread to other parts of the body. Due to lack of
target specificity and advocating high toxic adverse effect, chemotherapy is less
opted for cancer treatment.
• Nanotechnology has greatly revolutionized the therapy of cancer. It
minimizes the current limitations in conventional therapy. Thus, nanoparticle
increases the target specificity and therapeutic utility of drug.
• Nanotechnology is mainly concerned with the synthesis of nanoparticles of
variable sizes, shapes, chemical compositions and controlled dispersity and
their potential use for biomedical applications.
3. introductio
n
• Nanoparticle is a term may be defined as a particle having either one
or more dimensions of the order of 1000 nm size or less.
• Cancer nanotherapeutics is being implemented in new era
• Nanocarriers selectively use the exclusive pathophysiology of
cancerous cell by enhancing their retention effect, permeability and
the tumor microenvironment.
• Various pharmaceutical nanotechnology based systems which can be
termed as Nano pharmaceuticals are polymeric nanoparticules,
Magnetic nanoparticules, liposomes, carbon nanotubes, quantum
dots, dendrimers, metallic nanoparticules, polymeric nanoparticules,
etc.
4. CNT
• Carbon nanotubes (CNTs) are allotropes of carbon with a
cylindrical nanostructure.
• Nanotubes are members of the fullerene structural family. Their
name is derived from their long, hollow structure with the walls
formed by one-atom-thick sheets of carbon, called graphene.
• These sheets are rolled at specific and discrete angles, and the
combination of the rolling angle and radius decides the
properties.
• Carbon nanotubes (also known as buckytubes) are
shaped allotropes of carbon which have been constructed
with length-to-diameter ratio of up to 132,000,000:1
• CNTs are 50,000 times smaller than the average human hair
5. CNT
• CNTs are more dynamic compared with other nanomaterials in
their biological applications, and they are one of the most
interesting nanocarriers in scientific studies.
• CNTs have displayed obvious prospect that they can cross the
biological barriers as novel delivery systems.
• CNTs can also be applied in drug delivery and thermal ablation.
• They have the ability to enter cells, and this behavior is
independent of cell type and functional group at their surface.
Currently the detailed mechanisms of internalization (endocytosis
or needle like penetration) have not been completely explained
6. CNT
• The high area of CNTs can provide multiple sites for attachment
of different molecules, which makes polyvalent derivatization
possible.
• CNTs are able to adsorb or conjugate with a wide variety of
therapeutic molecules (drugs, proteins, antibodies, DNA,
enzymes, etc.). when bonded to CNTs, these molecules are
delivered more effectively and safely into cells than by
traditional methods
• Based on the number of layers, structures of CNTs are classified
into two types:
single-walled carbon nanotubes (SWCNTs)
multiwalled carbon nanotubes (MWCNTs)
7. Types
armchair zigzag chiral
Carbon nanotube structures of armchair, zigzag and chiral configurations. They
differ in chiral angle and diameter: armchair carbon nanotubes share electrical
properties similar to metals. The zigzag and chiral carbon nanotubes possess
electrical properties similar to semiconductors.
8. Types
o SWCNTs consist of a single graphene
cylinder with diameter varying
between 0.4 and 2 nm, and usually
occur as hexagonal close-packed
bundles.
9. Types
• MWCNTs consist of two to several
coaxial cylinders, each made of a
single graphene sheet
surrounding a hollow core. The
outer diameter of MWCNTs
ranges from 2 to 100 nm, while
the inner diameter is in the range
of 1–3 nm, and their length is 0.2
to several 𝜇m
10. Types
• Single layer of graphene
• Purity is poor
• Catalyst is required for synthesis
• Less accumulation in body
• Easily twisted
• Multiple layer of graphene
• Purity is high
• Can be produced without catalyst
• More accumulation in body
• Difficult to twist to
11. Synthes
is
Arc discharge
method
Laser ablation
method
Laser pulse-
graphite-oven-
1200℃- pressure
500 torr
Expensive so only
used for swcnt , high
yield
Chemical vapors
diposition method
Catalyst is deposited
on
substrate,nucleation
of catalyst
Atomized carbon
molecule deposited in
subsrtrate ,coated with
catalyst and nanotube
formed
swcnt
• Inert Gas
• Optical plasma control
• Catalyst
• Open air synthesis with
welding and torch
mwcnt
• Synthesis in liq nitrogen
• Mag field synthesis
• Plasma rotating arc discharge
12. synthes
is
flame synthesis
method
Swcnt formed in a
controlled flame from
HC fuel and catalyst
Catalyst:Iron
pentacarbonyl vapor
Silane solution
method
Substrate dipped in a
metal catalys such as
silane solution
Gas containing carbon
source such as ethylene
fed through the
substrate-
14. functionalizati
on
Functionalization of CNTs
• CNTs can be modified to improve their solubility by efficient methods,
which can be employed in several biological applications.
• Through functionalization of carbon nanotubes, i.e., the attachment of
appropriate chemical functionalities onto their conjugated sp2 carbon
scaffold, the prerequisites for facilitating the production of possible
applications of such nanostructures are established.
• The derivatized tubes exhibit improved properties with respect to
solubility and ease of dispersion, manipulation and processability, and
can be considered a true subdivision of organic molecules.
• Functionalization include attachment of COOH , AMINE , OH , AMIDE ,
THIOL, AMINO ACID,CARBOHYDRATE etc.
15. funtionlaizatio
n
• all kinds of active molecules can be linked to the functionalized
carbon nanotubes (f- CNTs), including peptides, proteins,
nucleic acids, and other therapeutic agents
• Moreover, the nonfunctionalized CNTs exhibit high cytotoxicity,
and it may be due to the insolubility of CNTs or the residual
metal catalysts in CNTs
20. diagnosi
s
Immunodetection of prostate cancer
cell using CNT with biomarker
• this are the electrochemical immunosensor using carbon nanotube
conjugate with multi labelled secondary antibody for highly sensitive
detection of cancer biomarker in serum and tissue lysate
• Greatly amplified sensitivity was attained by using bioconjugates
featuring horseradish peroxidase (HRP) labels and secondary antibodies
(Ab2) linked to carbon nanotubes (CNT) at high HRP/Ab2 ratio
• The signal from tumor cells was 2-6 times larger than the control signal
for no cancer cells
• SWNT immunosensors using the Ab2 -CNT-HRP bioconjugates gave
superior mass sensitivity to all commercial PSA immunoassays currently
available. The immunosensors require 10 times less sample than these
methods, and had a mass detection limit 10-100 times better than
commercial assays such as ELISA, Elecsys, IMX, and Tandem-R
21. Diagnosi
s
Carcinoembryonic antigen (CEA) is an important biomarker for the diagnosis of
cervical carcinomas, and pancreatic, gastric, colorectal, and lung cancer.
Various CNT-based electrochemical sensors were developed for CEA detection
utilizing anti-CEA antibodies as target recognition elements
22. delivery
Long boat delivery on CNTs of anticancer drug
like platinum ( cisplatin ,oxiplatin etc)
• The SWNT longboats produce platinum intracellular levels much
higher than those for the platinum unit administered in the
traditional manner. Efforts to produce potent platinum anticancer
drugs have been hindered by their inactivation in the body prior
to reaching the tumor. Longboat SWNTs provide an opportunity
to shuttle platinum compounds safely through this obstacle
course and into the cancer cell.
• functionalized soluble SWNTs can serve as “longboats” to carry
Pt(IV) prodrugs into cells through clathrin-dependent endocytosis
• SWNTs tethered to substrates by disulfide linkages use the
reducing environment of endosomes into which they are taken to
selectively release their drug only following cellular internalization
23. Delivery
Figure A has a
conventional prodrug of
cisplatin
And swcnt conjugate
cisaplatin via phospholipid
tethered amine linkage
Figure B indicate the
cytotoxicity of free
platinum drug and swnt
bound platinum drug
24. Treatme
nt
Due to optical
stimulation of swcnt
inside the cancer cell
Continu
ous NIR
Radiatio
n
Excessiv
e
heating
of swcnt
inside
the cell
swcnt
Folate
moiety
Tumour
marker
Cell
destruction
Selective
internalization into d
cancer cell
Selective destruction of carcinoma cell by CNTs
linked ligand using NIR radiation
(Photothermal therapy)
29. Treatme
nt
immunomodulation using CNTs is a possible
strategy to treat cancer.
• Glioma is a brain tumor that is able to evade the host immune system,
resulting in lack of benefit from conventional chemotherapy. This is
because glioma cells secrete the immunosuppressive cytokines such as
prostaglandins E and TGF-Beta and IL-10 .
• Macrophages have a preferential affinity towards CNTs when compared to
glioma cells . Using a GL261 murine intracranial glioma cancer model,
VanHandel and coworkers have developed an immunotherapy approach
using MWNTs based on the fact that macrophages prefer to engulf CNTs
compared with glioma cells.
• MWNTs caused an increase in the influx of macrophages into the glioma
cells. This was reported to be accompanied by an increase in the levels of
IL-10 expression, suggesting that immunomodulation using CNTs is a
possible strategy to treat cancer.
30. PK
• The biodistribution and pharmacokinetics of nanoparticles depend
on their physicochemical characteristics such as surface
functionalization, solubility, shape, aggregation, and chemical
composition.
• Both SWCNT and MWCNT were found to be excreted through the
renal route and observed to be intact in the excreted urine by
transmission electron microscopy
• One of the studies tells that 94% of cnts excreted in urine in
unchanged form and 6% in feces
• Other studies carried out on mice that CNTs can be broken down by
myeloperoxidase (MPO),a enzyme found on the neutrophils on mice
• all types of CNTs were rapidly cleared from all tissues and a
maximum blood circulation half-life of 3.5 h was determined
31. Toxicity
• One of the major causes of CNTs toxicity arises from the catalyst
residues left after their production. Synthesis of CNTs involves
the use of metal catalysts like Fe, Ni, Co, As, Mo etc. that are
quite toxic by themselves.
• These elements if not removed during the purification step,
tend to catalyze oxidative processes by free radical generation.
The ROS thus generated cause oxidative damage to cells and
membranes.
• E.g When CNTs are engulfed by macrophages, Nicotinamide
adenine dinucleotide phosphate–oxidase (NADPH-oxidase)
inside the cell produces superoxides (O2 ). Fe based catalysts
react with these superoxides to form hydroxyl ions, resulting in
oxidative stress and damage at the molecular level.
• highest purity CNTs have to be used which minimizes the toxic
effects of residual catalysts or surface oxidation
32. Conclusio
n
• Carbon nanotubes are one of the nanomaterials, which include
two forms. CNTs have been functionalized via covalent and
noncovalent interaction.
• CNTs combined with biosensors or other materials have proven
excellent implements for the therapeutic monitoring and the
diagnosis of diseases
• Good drug delivery of a anticancer drug due to their small size
and mass, their incredible mechanical strength, and their high
electrical and thermal conductivity
• CNTs are promising needle-like carriers of both small drug
molecules as well as macromolecules such as genes and
proteins. The needle-like shape of the CNTs enables them to
perforate cellular membranes and transport the carried
therapeutic molecules to the cellular components.
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