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

Abstract

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.