Current and future techniques for cancer diagnosis

BY

NITIN

TALREJA

Background & Introduction

CancerDevelopment of abnormal cells that divide uncontrollably which have the ability to infiltrate and destroy normal body tissue.

Techniques to DiagnoseThe 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.

Approaches to Diagnose 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 cancer Diagnosis

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-Enabled Blood Test 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.

Surface plasmon 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.

Ultrasensitive Immunosensor 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

Reference

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.