Photoinduced Cell Death Caused by Cyclometalated Iridium Complexes: Evaluation of Candidates and Elucidation of Mechanism

S, Smitha A. (2015) Photoinduced Cell Death Caused by Cyclometalated Iridium Complexes: Evaluation of Candidates and Elucidation of Mechanism. Masters thesis, Indian Institute of Science Education and Research Kolkata.

PDF (MS dissertation of Smitha A. S. (10MS75)) Smitha_AS_10MS75.pdf - Submitted Version Restricted to Repository staff only Download (592kB)

Abstract

Photodynamic therapy (PDT) is a promising anticancer therapeutic technique which is less invasive, more targeted and effective in many of the superficial cancers like skin and oral cancers. PDT is also useful in the treatment of other inflammatory conditions such as psoriasis, rheumatoid arthritis etc. Most of the superficial cancers are caused due to the exposure to inflammatory stimuli like UV and use of various carcinogenic substances such as tobacco. Development of inexpensive and targeted methods of treatment of these cancers is important for a country like India where the exposure to these carcinogenic stimulus is very common in daily life. Photodynamic therapy uses a photosensitizer which can be taken up by cancerous tissue and on irradiation with certain wavelength of light generates oxygen free radicals which cause the destruction of the cells. Thus, there is a selective ablation of cancerous cells using PDT which uses a photosensitizing compound combined with irradiation, which provides a high level of targeted killing. I have evaluated the function of a class of cyclometalated iridium complexes as efficient photosensitizing agents. These compounds are based on the scaffold of a cyclometalated Ir (III) polypyridyl complex (C2) reported by our lab earlier (Mandal S, Poria D.K. et al.). The different compounds have been synthesized by our collaborators in the Department of Chemical Sciences by altering the different ligands around the main iridium core. We have selected these compounds based on their high quantum yield, cellular uptake and minimization of self-quenching. I have found that three of these compounds showed specific localization in the endoplasmic reticulum (ER) and cause efficient photo induced cell death when illuminated by light at 405 nm. However they show very little cytotoxicity when not irradiated. I have explored the mechanism of photo induced cell death mediated by these compounds and have found that they cause generation of reactive oxygen species in the cells which finally leads to apoptotic cell death. Trying to elucidate the role of cellular mediators of this process I have fractionated cells treated by the compound C2 and have found that the C2 is specifically localized in the fraction corresponding to the ER. This will allow us to identify the cellular molecules with which C2 is interacting, which causes its ER localization and possibly helps in mediating the photo induced cell death.

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