WMIC 2015: Exhibitor Poster Award 2

Photodynamic therapy inhibited tumor growth by targeting upregulated translocator protein in mitochondria

Mingfeng Bai, University of Pittsburgh

Objectives: Photodynamic therapy (PDT) is proposed a less invasive therapeutic approach for treating cancers. Mitochondrion is an attractive target for developing novel PDT agents, as it produces ATP and regulates apoptosis. Current mitochondrial targeting photosensitizers (PSs) are based on cationic molecules which aims the negatively charged mitochondria membrane. However, such PSs are not specific for cancerous cells, which may result in unwanted side effect. Herein, we report a novel tumor mitochondria-specific PDT approach by targeting translocator protein (TSPO), an 18kDa mitochondrial protein up-regulated in multiple types of cancers including breast, prostate, and brain cancer.

Methods: We developed a novel TSPO-targeted photosensitizer, IR700DX-C6DAA1106, by conjugating a phthalocyanine dye IR700DX to a functional TSPO-targeted molecule C6DAA1106. We evaluated the phototherapeutic effect of IR700DX-C6DAA1106 both in vitro and in vivo.

Results: In vitro study indicated that IR700DX-C6DAA1106 phototherapy induced photo damage in TSPO positive breast cancer cells (MDA-MB-231) but not TSPO negative breast cancer cells (MCF-7). The treatment resulted in an apoptosis-like cell death, typically seen in mitochondria mediated cell death. Remarkably, in vivo phototherapy study suggested that, IR700DX-C6DAA1106-mediated phototherapy significantly inhibited the growth of MDA-MB-231 tumors.

Conclusions: In conclusion, we developed a novel mitochondria TSPO targeted photosensitizer IR700DX-C6DAA1106. This photosensitizer effectively induced apoptosis-like cell death in TSPO positive cancer cells. In addition, IR700DX-C6DAA1106 significantly inhibited tumor growth in TSPO positive tumor bearing mice. These combined data suggest that mitochondria TSPO-targeted photosensitizer appears to have great potential as a cancer phototherapeutic agent.

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