An effective zinc phthalocyanine derivative for photodynamic antimicrobial chemotherapy

Bacterial infection is a common clinical problem. The emergence of antibiotic resistant bacteria posts a severe challenge to medical practice worldwide. Photodynamic antimicrobial chemotherapy (PACT) uses laser light at specific wavelength to activate oxygen molecule in the human tissue into reactive oxygen species as antimicrobial agent. This activation of oxygen by laser light is mediated through a photosensitizer. Two key properties for potent photosensitizer are its absorbance of light in the infrared region (630-700 nm), which promotes tissue penetration depth, and the selective accumulation on bacteria instead of human tissue. We herein report a zinc phthalocyanine derivative, pentalysine beta-carbonylphthalocyanine zinc (ZnPc-(Lys)(5)) and its antimicrobial effects in vitro and in an animal infection model. This photosensitizer has strong capability to kill bacteria at 670 nm. Chemically, it is a water-soluble and cationic photosensitizer carrying positive charge under physiological pH, and can specifically target to bacteria which usually bears negative charges on its surface. Compared with anionic ZnPc counterparts, ZnPc-(Lys)(5) shows a higher phototoxicity toward bacteria. PACT studies of ZnPc-(Lys)(5) in experimental infection animal model showed a significant bacteria inhibition compared to controls, and high selectivity of ZnPc-(Lys)(5) toward bacteria. These findings suggest ZnPc-(Lys)(5) is a promising antimicrobial photosensitizer for the treatment of infectious diseases. (C) 2013 Elsevier B.V. All rights reserved.