Nanozyme-catalyzed oxygen release from calcium peroxide nanoparticles for accelerated hypoxia relief and image-guided super-efficient photodynamic therapy

摘要

Hypoxia within solid tumors severely limits the efficacy of photodynamic therapy (PDT). Biocompatible calcium peroxide nanoparticles (CaO2 NPs) have superior oxygen generating capacity for hypoxia relief but the relatively slow release of O-2 from CaO2 NPs hampers the PDT efficacy enhancement. Herein, manganese dioxide (MnO2) is applied as a nanozyme to facilitate O-2 release from CaO2 NPs. It is disclosed that the accelerated O-2 release ensures a rapid and efficient amplification of the O-2 level for an increased cytotoxic singlet oxygen production with chlorin e6 and leads to a down-regulated hypoxia-responsive protein expression, which eventually translates to a super-efficient PDT as evidenced by the complete eradication of mice bearing subcutaneous 4T1 tumors. Meanwhile, MnO2 imparts an MR T-1 imaging modality for tumor detection and treatment planning. These findings signify the essential role of accelerated and efficient hypoxia relief in PDT efficacy enhancement and provide an effective paradigm to overcome hypoxia-associated resistance for an enhanced therapeutic efficacy.