Photodynamic therapy (PDT) as a noninvasive therapy mode has attracted considerable attention in the field of oncotherapy. However, the PDT efficacy is restricted either by the tumor hypoxia environment or the inherent properties of photosensitizers (PSs) including bad water solution, photobleaching, and easy aggregation. Herein, we designed and synthesized a new two-dimensional (2D) metal-organic framework, Sm-tetrakis(4-carboxyphenyl)porphyrin (TCPP) nanosheets, by assembling transition metal ions (Sm3+) and PSs (TCPP), on which the catalase (CAT)-mimicking platinum nanozymes were then in situ grown for sufficient oxygen supply during PDT. The prepared Sm-TCPP with nanoplate morphology (∼100 nm in diameter) and ultrathin thickness (<10 nm) showed significantly enhanced 1O2 generation capacity due to the improved physicochemical properties and the enhanced intersystem crossing from heavy Sm nodes. More importantly, the CAT-mimicking Pt nanozyme on the Sm-TCPP nanosheets could effectively convert over-expressed H2O2 in the tumor microenvironment into O2 to relieve tumor hypoxia. Further, the triphenylphosphine (TPP) molecule was introduced to Sm-TCPP-Pt to develop a mitochondrion-targeting and O2 self-supply PDT system. The in vitro and in vivo experimental results based on the MCF-7 breast cancer model revealed that Sm-TCPP-Pt/TPP could relieve tumor hypoxia and the generated reactive oxygen species nearby intracellular mitochondria significantly induced cell apoptosis. This study offers an engineering strategy to integrate 2D PS-based metal-organic frameworks and nanozymes into a nanoplatform to surmount the pitfalls of traditional PDT.
Keywords: 2D metal−organic framework; mitochondrial targeting; nanozymes; photodynamic therapy; reactive oxygen species.