The anti-cancer potency of photodynamic therapy of a novel chlorin derivative Amidochlorin p6 (ACP)

Abstract

Photodynamic therapy (PDT) is a minimally invasive method in cancer treatment and has attracted considerable attention recently. In this paper, we have performed a detailed study of photodynamic activity of a chlorophyllous derivative, Amidochlorin p6 (ACP), and evaluated its potential as a photosensitizer in PDT. The singlet oxygen quantum yield (Φ_Δ), the photoreaction mechanisms in PDT, the anti-photobleaching ability in phosphate buffer saline (PBS), the photocytotoxicity and dark toxicity against HeLa cells, cellular uptake and the influence on the expression of survivin and cyclin-dependent kinase (CDK2), were all investigated. The title compound showed significant photocytotoxicity and negligible toxicity in dark, and remarkable photostability. Moreover, ACP could be uptaken by HeLa cells successfully at 20 min leading to damage of cancer cells under light, during which Type I and Type II photodynamic reactions occurred simultaneously on HeLa cells in PDT treatment, and the influence of Type I (the generation of hydroxyl radicals) is slightly larger than Type II (the generation of singlet oxygen). In addition, real-time fluorescent quantitative PCR (RT-qPCR) suggested that ACP could significantly regulate the expression of survivin, which partly explained why ACP could induce the HeLa cell apoptosis and accelerate cell death.