H2O2‐Activatable Liposomal Nanobomb Capable of Generating Hypoxia‐Irrelevant Alkyl Radicals by Photo‐Triggered Cascade Reaction for High‐Performance Elimination of Biofilm Bacteria

Abstract

AbstractHigh H2O2 levels are widely present at the infection sites or in the biofilm microenvironment. Herein, hemin with peroxidase‐like catalytic activity and its substrate, 2,2′‐azino‐bis(3‐ethylbenzothiazoline‐6‐sulfonic acid) (ABTS), are simultaneously introduced into a liposomal nanoparticle containing thermosensitive 2,2′‐azobis[2‐(2‐imidazolin‐2‐yl) propane] dihydrochloride (AIBI)‐loaded bovine serum albumin (BAG), rationally constructing an H2O2‐activatable liposomal nanobomb (Lipo@BHA) for combating biofilm‐associated bacterial infections with high performance. In the presence of H2O2, hemin can catalyze the conversion of ABTS into its oxidized form (ABTS·+) with strong near‐infrared (NIR) absorption, which produces photonic hyperpyrexia to cause the decomposition of AIBI into oxygen‐independent alkyl radicals (·R) and nitrogen (N2) microbubbles. The former not only directly damage bacterial cells but also significantly accelerates the oxidization of ABTS to ABTS·+ for augmenting photothermal‐triggered generation of ·R. Interestingly, the released N2 can induce transient cavitation to rupture lysosomal nanoparticle and improve the biofilm permeability, thereby enhancing the antibiofilm effect of Lipo@BHA. The proposed Lipo@BHA exhibits satisfactory multi‐mode combination antibacterial properties. Through endogenous H2O2‐activated cascade reaction, Lipo@BHA achieves remarkable hypoxia‐irrelevant ·R therapy of biofilm‐associated wound infections with low cytotoxicity and good in vivo biosafety. Therefore, this work presents a versatile H2O2‐activatable cascade ·R generation strategy for biofilm‐specific therapeutic applications.