Cancer receptors for targeting and treatment

Arun Kumar MauryaM.Tech Biotech

212BM2013

BackgroundEngineered nanoparticles have been used to provide

diagnostic, therapeutic and prognostic information about the status of disease.

Nanoparticles developed for these purposes are typically

modified with targeting ligands (such as antibodies, peptides or small molecules) or contrast agents using complicated processes and expensive reagents.

Cancer cells often overexpress characteristic surface receptors, which provide an opportunity for early diagnosis of the tumour.

Cancer receptor familyEGFR family

erbB1 (c-erbB) erbB2 (neu)

Insulin Receptor family IGF-1 (c-ros)

NeurotrophinsNGFR (trk)BDNFR (trk-B) NT3 R (trk-C)

FGF Family FGFR-1(fig) FGFR-2(K-sam)

PDGFR FamilyCSF-1R (c-fms)SLF R (c-kit)

Cancer receptor

Adopted from : Robert A. Weinberg / The Biology of Cancer

Engineered nanoparticles bind to cancer receptors

Magnetoferritin(M-HFn) nanoparticles

AuNPs conjugate with therapeutic and target peptide

Nanoparticles conjugate with monoclonal antibody

M-HFn nanoparticles

Iron oxide nanoparticles are encapsulated inside a recombinant human heavy-chain ferritin (HFn) protein shell, which binds to tumour cells that overexpress transferrin receptor 1 (TfR1).

The iron oxide core catalyses the oxidation of peroxidase substrates in the presence of hydrogen peroxide to produce a colour reaction that is used to visualize tumour tissues.

Adopted from : Nature nanotechnology doi: 10.1038/NNANO.2012.90

AuNPs conjugate with therapeutic and target peptide

Two peptides, therapeutic (p12) and targeted (CRGDK) conjugated on the surface of ultra-small AuNPs (2 nm).

Neuropilin-1 (Nrp-1) is a key receptor expressed by various cancer cell lines and plays an important role in growth and progression of cancer

Adopted from : A. Kumar et al. / Biomaterials 33 (2012) 1180e1189

Nanoparticles conjugate with monoclonal antibody

The humanized anti-HER2 monoclonal antibody trastuzumab (Herceptin) is useful in the treatment of Erb2-overexpressing breast cancers.

Adopted from : Emerging use of nanoparticles in diagnosis and treatment of breast cancerThe Lancet Oncology, Volume 7, Issue 8, August 2006, Pages 657–667

Conclusion:

 The use of nanoparticles will allow simultaneous tumour targeting and drug delivery in a unique manner by targeting specific cancer receptors.

Achieving rapid, low-cost and sensitive cancer diagnosis.

Reference:

1. Robert A. Weinberg,The Biology of cancer .

2. Kelong Fan1. et al, Magnetoferritin nanoparticles for targeting and

visualizing tumour tissues. Nature nanotechnology doi: 10.1038/NNANO.

(2012).90

3. A. Kumar et al. Gold nanoparticles functionalized with therapeutic and

targeted peptides for cancer treatment . Biomaterials 33 (2012) 1180 –

1189

4. Maksym V Yezhelyev et al, Emerging use of nanoparticles in diagnosis

and treatment of breast cancer . The Lancet Oncology, Volume 7, Issue 8,

(August 2006), 657–667

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