Nanozyme-catalyzed oxygen self-supplying mitochondria-targeting nanoplatform for precise photodynamic therapy

Abstract

Local hypoxia in tumors poses significant challenges to the effectiveness of oxygen-dependent photodynamic therapy (PDT). Herein, a versatile mitochondrial targeting and pH-responsive nanozyme platform (noted as Mito CPs-p) is developed for solving local hypoxia in tumors and enhancing the PDT efficiency. Mito CPs-p, which consists of carbon-dot-supported atomically dispersed platinum (CPs) with further surface modifications of triphenylphosphine (PPh3) and pH-responsive porphyrin polymers. The PDT of Mito CPs-p was activated in acidic tumor microenvironment and exposed platinum for catalyzing endogenous H2O2 decomposition to produce O2 at tumor sites, due to the hydrophobic-hydrophilic transition of pH-responsive porphyrin-containing polymers in Mito CPs-p from hydrophobic to hydrophilic, which can markedly enhance PDT efficiency. Besides, the rational integration of mitochondria-targeting will improve the bioavailability of reactive oxygen species and further strengthen the PDT efficiency. In vitro results indicated that Mito CPs-p has exhibited excellent mitochondrial targeting capability and the ROS yield of Mito CPs-p was dramatically amplified. In vivo data further revealed that the Mito CPs-p displayed superb therapeutic efficacy. Hence, the Mito CPs-p provides new insights for efficient PDT in hypoxia solid tumors.

Keywords

• Porphyrin
• Photodynamic therapy (PDT)
• Hypoxia tumors
• Mitochondria-targeting