Metal–Organic Framework Assisted and Tumor Microenvironment Modulated Synergistic Image-Guided Photo-Chemo Therapy

The complex tumor microenvironment (TME) and nonspecific drug targeting limit the clinical efficacy of photodynamic therapy in combination with chemotherapy. Herein, a metal–organic framework (MOF) assisted strategy is reported that modulates TME by reducing tumor hypoxia and intracellular glutathione (GSH) and offers targeted delivery and controlled release of the trapped chemodrug. Platinum(IV)-diazido complex (Pt(IV)) is loaded inside a Cu(II) carboxylate-based MOF, MOF-199, and an aggregation-induced-emission photosensitizer, TBD, is conjugated to polyethylene glycol for encapsulating Pt(IV)-loaded MOF-199. Once the fabricated TBD-Pt(IV)@MOF-199 nanoparticles are internalized by cancer cells, MOF-199 consumes intracellular GSH and decomposes to fragments to release Pt(IV). Upon light irradiation, the released Pt(IV) generates O₂ that relieves hypoxia and produces Pt(II)-based chemodrug inside cancer cells. Concomitantly, efficient reactive oxygen species generation and bright emission are afforded by TBD, resulting in synergistic image-guided photo-chemo therapy with enhanced efficacies and mitigated side effects.