In Vitro and In Vivo Demonstration of Human-Ovarian-Cancer Necrosis through a Water-Soluble and Near-Infrared-Absorbing Chlorin

With
the objective of developing efficient sensitizers for therapeutic
applications, we synthesized a water-soluble 5,10,15,20-tetrakis­(3,4-dihydroxyphenyl)­chlorin
(TDC) and investigated its in vitro and in vivo biological efficacy,
comparing it with the commercially available sensitizers. TDC showed
high water solubility (6-fold) when compared with that of Foscan and
exhibited excellent triplet-excited-state (84%) and singlet-oxygen
(80%) yields. In vitro photobiological investigations in human-ovarian-cancer
cell lines SKOV-3 showed high photocytotoxicity, negligible dark toxicity,
rapid cellular uptake, and specific localization of TDC in neoplastic
cells as assessed by flow-cytometric cell-cycle and propidium iodide
staining analysis. The photodynamic effects of TDC include confirmed
reactive-oxygen-species-induced mitochondrial damage leading to necrosis
in SKOV-3 cell lines. The in vivo photodynamic activity in nude-mouse
models demonstrated abrogation of tumor growth without any detectable
pathology in the skin, liver, spleen, or kidney, thereby demonstrating
TDC application as an efficient and safe photosensitizer.