Reactive Oxygen Species Synergistic pH/H₂O₂‑Responsive Poly(l‑lactic acid)-block-poly(sodium 4‑styrenesulfonate)/Citrate-Fe(III)@ZIF‑8 Hybrid Nanocomposites for Controlled Drug Release

Combination of photodynamic therapy and chemotherapeutic drugs is a promising strategy to achieve enhanced anticancer effect. In this study, a novel reactive oxygen species (ROS) synergistic pH/H₂O₂-responsive nanocomposite has been prepared from the self-assembly of poly­(l-lactic acid)-block-poly­(sodium 4-styrenesulfonate) in aqueous solution, followed by addition of ferric citrate (Cit-Fe­(III)) through electrostatic interaction and growing ZIF-8 among the surface of the particles. Upon H₂O₂ and visible light stimuli, efficient ROS such as hydroxyl radicals (^•OH) and sulfate radicals (SO₄^•–) can be generated through the catalyst of Cit-Fe­(III). Meanwhile, sulfonate-containing polymeric vesicles are disassembled through oxidization by ROS, and the encapsulated doxorubicin (DOX) will gradually diffuse into the ZIF-8 (one type of metal–organic framework, MOF) channels. The gatekeepers, ZIF-8, will collapse only under low pH condition, and a burst drug release is achieved. In the presence of H₂O₂ and pH stimuli upon visible light exposure, the prepared DOX-loaded nanocomposite exhibits good selectivity for both generating ROS and releasing drug in tumor cell instead of normal cell. The merits of nanocomposites such as good biocompatibility and especially the synergistic effect of chemo-photodynamic therapy make the material a highly promising candidate for drug delivery system in chemo-photodynamic therapy.