Electrostatically assembled gold nanocluster-enhanced porphyrinic metal-organic framework nanozymes for oxygen-boosted photodynamic therapy of hypoxic tumors

Tumor hypoxia severely limits the therapeutic efficacy of photodynamic therapy (PDT), which relies on molecular oxygen to generate cytotoxic reactive oxygen species (ROS). Herein, an electrostatically assembled gold nanocluster–porphyrinic metal-organic framework nanozyme (AuNCs-pMOF) was developed as an oxygen-supplying platform for enhanced PDT of hypoxic tumors. By integrating catalase-mimetic gold nanoclusters (AuNCs) with a porphyrin-based metal-organic framework (pMOF), the resulting AuNCs-pMOF nanocomposite catalyzes the decomposition of endogenous H 2 O 2 to provide local O 2 , thereby supporting 1 O 2 /ROS generation under oxygen-limited conditions. In vitro studies demonstrated that AuNCs-pMOF maintained efficient ROS production and phototoxicity under hypoxia, whereas pristine pMOF showed reduced PDT efficacy. In vivo antitumor evaluation further confirmed that AuNCs-pMOF combined with light irradiation markedly inhibited tumor growth and induced pronounced tumor cell death, while showing favorable short-term tolerability under the tested experimental conditions. Overall, this work presents an electrostatically assembled oxygen-supplying nanozyme platform to mitigate oxygen shortage during PDT and enhance therapeutic efficacy against hypoxic solid tumors.