Enhancing PDT drug delivery by enzymatic cleavage of porphyrin phosphates

A new anionic porphyrin-phosphate conjugate has been made as the substrate of phosphatase to evaluate its cellular-uptake and potential targeting on cancer cells, taking advantage of the over-expression of phosphatases associated with the development of cancers. The phosphate groups increase the hydrophilicity of porphyrin dityrosine phosphate and facilitate its formulation in aqueous solvent. Upon hydrolysis by phosphatase after cellular uptaking, the more hydrophobic porphyrin-dityrosine promises to give better cellular retention. Indeed, the phosphate conjugate displayed a much better PDT effect than that of the parent porphyrin at the same concentration (10 mu M) and light dosage on HeLa cells, indicating the enzyme-cleavage reaction occurred in HeLa cells plays a role. Photosenzitizers utilizing enzyme-cleavage might be a promising approach for photodynamic therapy.