Current and future techniques for cancer diagnosis

Background& Introduction
 Cancer
Development of abnormal cells that divide uncontrollably which have
the ability to infiltrate and destroy normal body tissue.
 Techniques to Diagnose
The methods and the procedure involved generally depends on the
locality as well as the type of cancer.
 Nanotechnology is one of the emerging
Domain to be used in detection, prevention
And Treatment of Cancer.

The design, characterization, production, and application of structures, devices,
and systems by controlled manipulation of size and shape at the nanometer scale
(atomic, molecular, and macromolecular scale) that produces structures, devices
and systems with at least one novel/superior characteristic or property.

Nanotechnology in cancerDiagnosis
Different techniques which
involves the use of nanoparticles,
nanoprobes and nanofibres are
now used for different purposes
as shown in the figure.
Nanoshells, carbon nanotubes,
quantum dots, supermagnetic
nanoparticles, nano wires,
nanodiamonds, dendrimers, and
recently synthesized nanosponges
are some of the materials used for
cancer detection.

Detection By Gnps
 GNPs are the colloidal suspension of gold particles of nanometer
sizes.
 Gold nanoparticles (GNPs) have been in the bio-imaging spotlight
due to their special optical properties.
 GNPs with strong surface-plasmon-enhanced absorption and
scattering have allowed them to emerge as powerful imaging labels
and contrast agents.
 They have better absorption and scattering bands than conventional
organic dyes.

Gold Nanoparticle-EnabledBloodTest for Early
Stage Cancer Detection
When citrate ligands-capped gold nanoparticles are mixed with blood sera, a protein
corona is formed. Using a two-step gold nanoparticle-enabled dynamic light scattering
assay, we discovered that the amount of human immunoglobulin G (IgG) in the gold
nanoparticle protein corona is increased in prostate cancer patients compared to
noncancer controls.

The future approach
 For GNPs as stable and versatile molecular imaging agents, a
complementary oligonucleotide-based approach has been
proposed.
 A 5′-thiol-modified and 3′-NH2-modified oligonucleotide was
coated onto the nanoparticles and subsequently conjugated with
anti-EGFR proteins through DNA-DNA hybridization.
 Through this study, gold nanoparticles have proven to be effective
reflectance contrast agents for molecular imaging.

Surfaceplasmon Coupling
 A recent study has been conducted where plasmon resonance
coupling was used for in vivo molecular imaging of carcinogenesis.
 Anti-EGFR antibodies were conjugated to gold nanoparticles and
these nanoparticles were used to obtain information on the over-
expression and nanoscale spatial relationship of EGFRs in cell
membranes.

Advantage
 EGFR-mediated aggregation of GNPs results in color
shift and a contrast ratio much superior than those with
fluorescent dyes when normal and precancerous
epithelium were imaged in vivo.
 Dynamic light scattering (DLS) analysis can also be
used for biomarker sensing. ???

Dynamic Light Scattering
 A combination of GNPs and gold nanorods conjugated with anti-
Prostate Specific Antigen (PSA) antibody was used as a one-step
homogeneous immunoassay for cancer biomarker detection.
 Through DLS analysis, the relative ratio of nano-particle
aggregate versus non aggregated nano-particles can be measured
quantitatively.

And The Modifications
 GNP film electrodes have also been proven to be useful in
detecting cancer biomarker proteins. By applying multilabeled
detection antibody-magnetic bead bioconjugates, an ultrasensitive
electrochemical immunosensor for cancer biomarker proteins has
been designed.

QUANTUM DOTS
 Quantum dots (QDs) are semiconducting, light-emitting
nanocrystals that have emerged as a powerful molecular imaging
agent since their discovery.
 QDs are an exciting material to work with due to their unique
optical properties compared to traditional organic fluorescent
labels.

 QDs can be used as signal amplifying agents in ultrasensitive
cancer biomarker detection.
 A recent study has been conducted with QD functionalized
nanoparticles in immunoassays, targeting alpha-fetoproteins
(AFPs). CdTe QDs have been coated on SiO2 particles.
 Increased amount of QDs per biomarker make the detection more
sensitive, thus enabling detection even at low concentration.

UltrasensitiveImmunosensor for Lung Cancer
Biomarker, hTERT
 Ultrasensitive Graphene Oxide (GO) based electrochemical
immunosensor to detect human telomerase reverse transcriptase
(hTERT), a lung cancer biomarker.
 The immuno-electrode-has been fabricated by covalent
immobilization of rabbit anti-hTERT antibodies (Ab) onto GO
films on ITO coated glass.
 The Fourier Transform Infrared (FTIR) spectroscopic studies
confirms the presence of diverse organic functional groups (-
COOH, -CHO, -OH) of GO, and the binding (anti-hTERT) onto
GO/ITO electrode.
 The low level detection of hTERT warrants the realization of point-
of-care device for early detection of lung/oral cancer through oral
fluids

Carbon Nanotubes
 CNTs have been constantly in the spotlight and have
emerged as a powerful sensing vehicle due to their
exciting properties.
 The conductance of the semiconducting CNT changes
when biomolecules are adsorbed on the walls, causing
changes in local electrostatic environment.
 Many exceptional properties of CNTs allow them to be
applied for sensing biomarkers electrochemically;
 CNTs provide high surface-to-volume ratios, mediate
fast electron-transfer and can be functionalized with
almost any desired chemical species.

A multilayered enzyme-coated carbon nanotube design has been studied as an
ultrasensitive chemiluminescence immunoassay (CLIA) for detecting AFP in
human serum samples. Horse radish peroxide (HRP) was absorbed into
MWNTs, allowing maximized ratio of HRP/antibodies for sensitivity
enhancement. After separating the MWNT-AFP by applying magnetic beads
with antibodies, bromophenol blue (BPB) and H2O2 was added to the
separated solution. The chemiluminescence reaction was triggered by
injecting luminol into the solution.

MWNT functionalized with fluorescein isothiocyanate (FI) and folic
acid (FA) modified amine-terminated dendrimers. FA is for targeting
cancer cells that over-expresses FA receptors and FI dye for imaging.

Some Other techniques…
 Various nanowires have also been applied to biomarker
detection including silicon nanowires In2O3 nanowires, gold
nanowires conducting polymer nanowires.
 Vascular endothelial growth factor (VEGF), yet another cancer
biomarker, has been detected electrically with functionalized
SiNWs.
 A lung cancer biomarker, interleukin-10 (IL-10) and
osteopontin (OPN), has been detected using silica nanowires as
templates, through electrochemical alkaline phosphatase (AP)
assay.
 A lung cancer biomarker, interleukin-10 (IL-10) and
osteopontin (OPN), has been detected using silica nanowires as
templates, through electrochemical alkaline phosphatase (AP)
assay.

Nanoflare..
 A nanoparticle agent that is capable of simultaneously detecting two
distinct mRNA targets inside a living cell. These probes are spherical
nucleic acid (SNA) gold nanoparticle (Au NP) conjugates consisting of
densely packed and highly oriented oligonucleotide sequences
 A NanoFlare is designed to recognize a specific genetic code snippet
associated with a cancer. The core nanoparticle, only 13 nanometers in
diameter, enters cells, and the NanoFlare seeks its target. If the genetic
target is present in the cell, the NanoFlare binds to it and the reporter
“flare” is released to produce a fluorescent signal. The researchers then
can isolate those cells.
NanoFlares light up (red clouds)
individual cells if a cancer (in this study,
breast cancer) biomarker (messenger
RNA, blue) is detected by recognition
DNA (green) molecules coated on gold
nanospheres and containing a fluorescent
chemical (red) reporter flare (credit:
Tiffany L. Halo et al./PNAS)

CONCLUSION
 Nanotechnology has brought revolution in cancer detection and
treatment. It has capability to detect even a single cancerous cell in
vivo and deliver the highly toxic drugs to the cancerous cells
 we finally have the ability to understand malfunctions of the most
complex biological systems at the atomic and molecular level.
 As we progress further into our research, the ability to devise
progressively more innovative and ingenious atomic-scale
solutions and to make them real will allow us to develop amazingly
complex and effective weapons against any ailment.
 However, the field of nanotechnology is still quite young and we
are only beginning to understand its capabilities and potentials.
……………………

…..
 This review summarized recent developments in cancer
detection methods with an emphasis on nanotechnology
 The low detection limit obtained by nanotechnology is
expected to contribute immensely to the early detection and
accurate prognosis of cancers. Since it is of huge importance
to be able to diagnose cancer as early as possible
 It must be however noted that these new technologies must be
validated critically before applying them for clinical
diagnosis.
THANKYOU  

REFERENCES
 1) Hahn, W. C.; Weinberg, R. A. Nat. Rev. Cancer, 2002, 2, 331–
341.
 2) Liotta, L.; Petricoin, E. Nat. Rev Genet, 2000, 1, 48–56.
 3) Henglein, A.; Chem. Rev. 1989, 89, 1861–1873.
 4) Alivisatos, P.; Nat. Biotechnol, 2004, 22, 47–52.
 5) Alivisatos, A .P.; Gu, W. W.; Annu. Rev. Biomed. Eng. 2005, 7,
55–76.
 6) Golub, T .R.; Slonim, D. K.; Tamayo, P.; Huard, C.;
Gaasenbeek, M.; Science, 1999, 286, 531–537.
 7) Woolley, A. T.; Guillemette, C.; Cheung, C. L.; Housman, D. E.;
Lieber, C. M.; Nat.Biotechnol, 2000, 18, 760–763.
 8) Hahm, J.; Lieber, C. M.; Nano Lett, 2004, 4, 51–54.
 9) Patri, A. K.; Curr. Opin. Chem. Biol, 2002, 6, 466-468.
 10) Andresen, T. L.; Prog. Lipid Res, 2005, 44, 68-72.

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