Catalase–albumin cluster incorporating protoporphyrin IX: an O2 generating photosensitizer for enhanced photodynamic therapy

Abstract

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.