Anti-EGFR antibody conjugated gold nanoparticles: A promising strategy for molecular targeting of epithelial carcinoma.
Posted by: Rama Saad in TherapeuticsDespite great advances in cancer therapy, conventional therapies are still implementing drawbacks and dilemmas that drives cancer research to consider other strategies to overcome the drawbacks implicated by conventional cancer therapy. The cancer treatment using anticancer agents possesses many adverse events related to bone marrow suppression and death of other rapidly proliferating cells is resulting from the either of the two following reasons:
- The narrow therapeutic index of anticancer agents that is in many cases hard to adjust with the inter-individual Pharmacokinetic &/or pharmacogenetic variation among cancer patients.
- The lack of specificity in most of anticancer agents systemically administered where anticancer agents kill both tumor cells and healthy cells.
Both of the above facts driven cancer therapy research in to many different aspects in the hope of optimizing the therapy & providing new techniques to get over the drawbacks of conventional therapy; The pharmacokinetics & /or pharmacogenetics, gene therapy in addition to the targeting therapy including the nanotherapy.
Professor Mostafa El Sayed was awarded the 2007 US National Medal of Science for his huge contribution in the field of nanotherapy in cancer as a molecular targeting approach that overcomes side effects of conventional cancer therapy. The idea lies in two main aspects: The first is molecular targeting & the second is photothermal destruction of malignant cells. The technique encompasses injecting gold nanoparticles conjugated with anti- Epidermal Growth Factor Receptor “anti -EGFR” monoclonal antibody , where the anti-EGFR is responsible for the the specific targeting which is molecularly based on the fact that epithelial carcinoma cells, particularly over-expresses “EGFR”. Regarding the tumor cidal effect it is mainly dependent on the photothermal destruction which is the role of the laser beam & gold nanoparticles, where particular nano size of gold makes it able to absorb light in Near Infra Red Region , which is the region where optical penetration is optimal & scatter laser beam and convert the light energy to thermal energy that is able to damage cell membrane and release the digestive enzymes and hence the death of cancer cells.
Image credit: www.gatech.edu
The choice of the laser light is a matter of the cancer location , where in case of cancer under the skin, Near Infra Red “NIR” laser light is recommended for its larger penetration depth. Gold particles are especially used because they are easily bioconjugated & they served as photoabsorbers due to overlap of absorption band of their specific nanosize with with argon laser beam. The gold nanoparticles are having a silica core and a gold shell & their absorption in the NIR is tuned by adjusting gold layer thickness as well as the size of silica core.
The pioneering success of the technique has been proved effective upon accumulation of Anti-EGFR antibody conjugated gold nanoparticles selectively in carcinoma cells and survival of benign cells as demonstrated by microscopic pictures of both benign & cancer cells as follows:
Gold nanoparticles are concentrated in cancer cells. “Pic 1”
Image credit: www.gatech.edu
Gold nanoparticles are not retained in benign cells. “Pic 2”
Image credit: www.gatech.edu
References:
- Ivan H. El Sayed, Xiaohua Huang, Mostafa A. El Sayed, ” Selective laser Photo-thermal therapy of epithelial carcinoma using anti-EGFR antibody conjugated gold nanoparticles”, Cancer Letters 239 (2006) 129-135.
- Erin B. Dickerson, Erick C. Dreaden, Xiaohua Huang, Ivan H. El Sayed,Hunghao Chu, Sujatha Pushpanketh, John F. Mcdonald, Mostafa A. El Sayed, ” Gold nano assiated near-infrared Plasmonic Phototheramal Therapy (PPTT) of squamos cell carcinoma in mice”, Cancer Letters 269 ( 2008) 57- 66.