Hierarchical core–shell nanoplatforms based on sacrificial template-directed ZnO2@ZIF-8 for spatiotemporally controlled and self-augmented chemodynamic–photothermal antibacterial therapy

Sacrificial template strategy builds ZnO 2 @Hemin-ZIF-8 core-shell structure. • The seamless ZIF-8 shell prevents premature ZnO 2 leakage at physiological pH. • Hierarchical ZnO 2 @Hemin-ZIF-8@PB (ZHZHP) enables on-demand H 2 O 2 release. • ZHZHP enables dual-nanozyme cascade-based CDT and PTT to eradicate bacteria. • ZHZHP orchestrates anti-inflammation and angiogenesis to accelerate wound healing. Chemodynamic therapy (CDT) has emerged as a promising strategy for combating bacterial infections; however, the scarcity of endogenous H 2 O 2 within infection sites often bottlenecks therapeutic efficacy. Herein, a pH-responsive, H 2 O 2 self-supplying nanoplatform is meticulously engineered for spatiotemporally controlled chemodynamic–photothermal antibacterial therapy. This platform leverages ZnO 2 nanoparticles dual-role cores and sacrificial template to drive the in situ epitaxial growth of dense ZIF-8 shells (optionally encapsulated with Hemin), yielding the core–shell ZnO 2 @ZIF-8 (or ZnO 2 @Hemin-ZIF-8) intermediate. Stepwise surface engineering with hyaluronic acid (HA) and Prussian blue (PB) leads to the formation of a hierarchical core–shell structured ZnO 2 @Hemin-ZIF-8@HA@PB nanoplatform (ZHZHP). Under neutral physiological conditions, ZHZHP exhibits excellent stability as the interracially-bonded ZIF-8 shell effectively shields the ZnO 2 core from premature hydrolysis. Conversely, within the weakly acidic infection microenvironment, ZHZHP undergoes programmed disassembly, triggering the on-demand release of H 2 O 2 . Simultaneously, Hemin and PB act as peroxidase mimics to catalyze the conversion of liberated H 2 O 2 into highly toxic hydroxyl radicals (‧OH) via dual nanozyme cascades, while the PB component provides robust photothermal conversion under 808 nm NIR irradiation. This synergistic CDT/PTT approach achieves complete eradication of S. aureus and E. coli at an extremely low concentration of 50 μg mL −1 and demonstrates remarkable efficacy in disrupting both immature and mature biofilms. In vivo assays further confirm that ZHZHP significantly accelerates infected wound healing through potent antimicrobial and anti-inflammatory activities, alongside the promotion of angiogenesis. With high biocompatibility and negligible toxicity, ZHZHP represents a sophisticated strategy for the clinical management of refractory wound infections. Download: Download high-res image (156KB) Download: Download full-size image