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

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 O2 from CaO2 NPs hampers the PDT efficacy enhancement. Herein, manganese dioxide (MnO2) is applied as a nanozyme to facilitate O2 release from CaO2 NPs. It is disclosed that the accelerated O2 release ensures a rapid and efficient amplification of the O2 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 T1 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.