Enhanced in vitro photocytotoxicity of water-soluble dendritic pheophorbide-a

Photosensitizers can produce highly reactive singlet oxygen with exposure to visible light and are used in photodynamic therapy to treat a variety of tumors. We report on the synthesis of triethylene glycol dendron-conjugated pheophorbide-a 5, a novel photosensitizer. The characteristic absorption bands (Soret and Q-bands, lambda(max) = 405 and 670 nm, respectively) of 5 were appeared clearly in aqueous solution, due to the improved water-solubility of the dendron moiety. The value of singlet oxygen quantum yield of 5 (Phi(Delta) = 0.22) was higher than free pheophorbide-a (Phi(Delta) = 0.17) as reference in aqueous solution. Compound 5 also exhibited an enhanced in vitro phototoxicity than pheophorbide-a (PhA) in the concentration range of 1.0-5.0 mu g/mL: cell viability in cells treated with 5 was reduced by similar to 20%, indicating a cell death rate of similar to 80%, while PhA treatment resulted in a cell death rate of only about 10%. These results indicate that 5 will likely be more efficient in PDT applications. Compared with free PhA, compound 5 showed highly enhanced singlet oxygen generation ability and in vitro photocytotoxicity.