Catalase–albumin cluster incorporating protoporphyrin IX: an O2 generating photosensitizer for enhanced photodynamic therapy†
Photodynamic therapy (PDT) is a non-invasive cancer treatment using reactive oxygen species (ROS) generated by light irradiation. An excited state photosensitizer produces active radicals (e.g. O2˙− and OH˙) by electron transfer reactions (type I), while an excited triplet state photosensitizer generates singlet O2 (1O2) by direct energy transfer to molecular O2 (type II). This report describes the synthesis and PDT activity of the hemoprotein-based photosensitizer combined with O2 production capability. Covalent wrapping of a catalase (Cat) with human serum albumins (HSAs) yielded the core–shell structured protein cluster Cat-HSA5, in which an average of five HSA molecules are bound to the Cat center. Cat-HSA5 retained the high enzymatic activity of the hydrogen peroxide (H2O2) disproportionation reaction. Subsequently, the incorporation of protoporphyrin IX (PP) into an individual HSA unit resulted in a Cat-(HSA-PP)5 cluster. The 1O2 generation ability of Cat-(HSA-PP)5 was equivalent to that of the HSA–PP complex. Cytotoxicity with light irradiation was evaluated using HeLa cells. Cat-(HSA-PP)5 demonstrated higher PDT activity than the HSA–PP complex. The Cat core provoked conversion of endogenous H2O2 to O2 efficiently in the cells to facilitate 1O2 formation in large amounts. Cat-(HSA-PP)5 is a unique dual functional hemoprotein cluster (O2 generation and photosensitization) that can achieve enhanced PDT.