The formation of biofilms is closely associated with persistent and chronic infections, and physiological heterogeneity such as pH and oxygen gradients renders biofilms highly resistant to conventional antibiotics. To date, effectively treating biofilm infections remains a significant challenge. Herein, we report the fabrication of micellar nanoparticles adapted to heterogeneous biofilm microenvironments, enabling nitric oxide (NO) release through two distinct photoredox catalysis mechanisms. The key design feature involves the use of tertiary amine (TA) moieties, which function as sacrificial agents to avoid the quenching of photocatalysts under normoxic and neutral pH conditions and proton acceptors at acidic pH to allow deep biofilm penetration. This biofilm-adaptive NO-releasing platform shows excellent antibiofilm activity against ciprofloxacin-resistant Pseudomonas aeruginosa (CRPA) biofilms both in vitro and in a mouse skin infection model, providing a strategy for combating biofilm heterogeneity and biofilm-related infections.

生物膜的形成与持续性和慢性感染密切相关，pH和氧气梯度等生理异质性使得生物膜对传统抗生素具有高度耐药性。迄今为止，有效治疗生物膜感染仍然是一个重大挑战。在此，我们报道了适应异质生物膜微环境的胶束纳米粒子的制造，能够通过两种不同的光氧化还原催化机制释放一氧化氮（NO）。关键的设计特点涉及使用叔胺 (TA) 部分，其充当牺牲剂，以避免在常氧和中性 pH 条件下淬灭光催化剂，并在酸性 pH 条件下充当质子受体，以允许深层生物膜渗透。这种生物膜适应性NO释放平台在体外和小鼠皮肤感染模型中都显示出针对耐环丙沙星铜绿假单胞菌（CRPA）生物膜的优异抗生物膜活性，为对抗生物膜异质性和生物膜相关感染提供了策略。