Abstract B56: Organelle targeted photodynamic therapy

Abstract

Abstract The success of a cancer treatment is directly related to its ability to selectively kill cancer cells. Photodynamic therapy (PDT) with a photosensitizer (PS) that targets mitochondria causes a prompt release of cytochrome c into the cytoplasm and activation of caspases-9 and -3, among other caspases, that are responsible for initiating cell degradation. Photofrin is the FDA approved drug for PDT. Mitochondria have repeatedly been implicated as primary targets of porphyrin mediated PDT. However, a systematic study to direct the PDT drugs towards their cellular target, mitochondria of the cancer cell, is not yet fully explored. Phthalocyanins (Pc) are a class of compounds, which are known to successfully address the drawbacks exhibited by the porphyrin-based compounds. PDT, using the second-generation Pc, causes mitochondrial damage and induces apoptosis. However, the Pc molecules are hydrophobic and must be encapsulated within a liposomal formulation for successful delivery. Given that most effective PDT drug candidates act on the mitochondria of cancer cells and their hydrophobicity require suitable delivery vehicles for their intracellular accumulation, we hypothesize that the construction of engineered targeted drug delivery systems to direct PDT drugs to the mitochondria of the cancer cells would allow an effective phototherapeutic action. This would result in a higher local concentration of singlet oxygen in the mitochondria of cancer cells. In order to study this hypothesis, we have initiated the synthesis of a series of mitochondria targeting polymers to study nanoparticle (NP) assisted targeted delivery and anticancer properties of metallo phthalocyanins. The synthesis and biological activity of these constructs will be discussed. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the Second AACR International Conference on Frontiers in Basic Cancer Research; 2011 Sep 14-18; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2011;71(18 Suppl):Abstract nr B56.