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

被引：0

作者：

Yang, Ke ^{[1
]}

Wang, Li ^{[1
]}

Chen, Jinyi ^{[1
]}

Wang, Zefeng ^{[1
]}

Li, Junqin ^{[1
]}

Chen, Xi ^{[1
]}

Fu, Shuting ^{[1
]}

Hai, Luo ^{[2
,3
,4
]}

Deng, Le ^{[1
]}

He, Dinggeng ^{[1
]}

机构：

[1] Hunan Normal Univ, Inst Interdisciplinary Studies, Coll Life Sci, Changsha 410081, Peoples R China

[2] Chinese Acad Med Sci & Peking Union Med Coll, Cent Lab, Shenzhen 518116, Peoples R China

[3] Chinese Acad Med Sci & Peking Union Med Coll, Natl Canc Ctr, Shenzhen Key Lab Epigenet & Precis Med Canc, Natl Clin Res Ctr Canc,Canc Hosp, Shenzhen 518116, Peoples R China

[4] Chinese Acad Med Sci & Peking Union Med Coll, Shenzhen Hosp, Shenzhen, Peoples R China

来源：

ADVANCED HEALTHCARE MATERIALS | 2024年

基金：

中国国家自然科学基金;

关键词：

H2O2; alkyl radical; bacterial biofilm; cascade reaction; liposome; THERAPY;

D O I：

10.1002/adhm.202402136

中图分类号：

R318 [生物医学工程];

学科分类号：

0831 ;

摘要：

High 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<middle dot>(+)) with strong near-infrared (NIR) absorption, which produces photonic hyperpyrexia to cause the decomposition of AIBI into oxygen-independent alkyl radicals (<middle dot>R) and nitrogen (N-2) microbubbles. The former not only directly damage bacterial cells but also significantly accelerates the oxidization of ABTS to ABTS<middle dot>(+) for augmenting photothermal-triggered generation of <middle dot>R. Interestingly, the released N-2 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 <middle dot>R therapy of biofilm-associated wound infections with low cytotoxicity and good in vivo biosafety. Therefore, this work presents a versatile H2O2-activatable cascade <middle dot>R generation strategy for biofilm-specific therapeutic applications.

引用

页数：17