化学
溴化物
体内
生物膜
铜绿假单胞菌
纳米颗粒
阳离子聚合
生物物理学
细菌
材料科学
纳米技术
高分子化学
有机化学
生物
遗传学
生物技术
作者
Lin Wang,Fangzhou Chen,Nier Wu,Lingfei Hu,Haihua Xiao,Hanchen Zhang,Dongsheng Zhou
出处
期刊:Advanced Science
[Wiley]
日期:2025-04-02
卷期号:12 (22): e2417469-e2417469
被引量:6
标识
DOI:10.1002/advs.202417469
摘要
Sonodynamic therapy (SDT) has good feasibility to deeply seated infections, but SDT alone is insufficient being highly effective against multidrug-resistant (MDR) bacteria. SDT combined with triphenylphosphanium bromide (P+Ph3Br-) is expected to solve this problem. This work develops a pseudo-conjugated polymer PFCPS-P containing cationic P+Ph3Br--modified sonosensitizer FCPS (FCPS-P) and ROS-sensitive thioketal bonds. PFCPS-P is assembled with DSPE-mPEG2000 to generate nanoparticle NPFCPS-P. FCPS has SDT effect and generates ROS under ultrasound (US) stimulation. ROS triggers the degradation of NPFCPS-P and release of FCPS-P, endowing highly favored biosafety. FCPS-P targets to bacterial surface through electrostatic interaction and achieves bacterial killing under a synergistic action of SDT and P+Ph3Br-. In vitro, NPFCPS-P+US gives >90% inhibition rates against MDR ESKAPE pathogens, moreover, it causes bacterial metabolic disorders including inhibited nucleic acid synthesis, disordered energy metabolism, excessive oxidative stress, and suppressed biofilm formation and virulence. In mice, NPFCPS-P+US exhibits a 99.3% bactericidal rate in Pseudomonas aeruginosa-induced sublethal pneumonia and renders a 90% animal survival rate in lethal pneumonia, and additionally immunological staining and transcriptomics analyses reveal that NPFCPS-P+US induces inhibited inflammatory response and accelerated lung injury repair. Taken together, NPFCPS-P+US is a promising antibiotics-alternative strategy for treating deeply seated bacterial infections.
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