ABSTRACT Organic semiconducting polymer nanoparticles (SPNs) have emerged as promising therapeutic agents due to their favorable optical properties and biocompatibility. However, their application in infected wound healing remains limited by challenges such as poor structural stability and difficulty in post‐synthetic modification. In this study, we present a mild and modular approach to fabricate SPN‐MOF hybrid nanoframes by embedding SPNs within zeolitic imidazolate framework‐8 (ZIF‐8‐MOF) matrices. These hybrid nanostructures possess tunable optical and physicochemical properties, enabling broad applicability in biomedical contexts. Among the nanostructures, PFOBT‐MOF demonstrated efficient light‐induced reactive oxygen species generation, which was significantly amplified through oxygen loading. MOF's porous architecture functions as an oxygen reservoir, alleviating hypoxia in pathological tissues, while surface modification with Pluronic F127 enhances biocompatibility, stability, and systemic performance. The optimized nanoframes exhibited potent antibacterial activity both in vitro and in a murine Escherichia coli ‐infected wound model under light irradiation. Overall, this work establishes SPN‐MOFs as a versatile and effective platform for enhanced therapeutic efficacy through the integration of phototherapy with gas and drug delivery in complex clinical scenarios.
Zhu et al. (2026) studied this question.