Zhang Rui, Mao Danhua, Fu Yiyong, Ju Rong, Wei Guoqing
Chengdu Women's and Children's Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 611731, China.
Theranostics. 2025 Apr 28;15(12):5953-5968. doi: 10.7150/thno.114344. eCollection 2025.
The pursuit of effective antibacterial strategies aimed at mitigating pathogenic bacterial infections while minimising drug resistance remains of paramount importance. A combinational therapeutic strategy that integrates distinct treatment components can enhance overall efficacy and mitigate undesired effects, thereby exhibiting considerable promise in combating bacterial infections. In this study, a meticulously engineered self-assembling hybrid nanoprodrug (CPBP NPs) has been devised, functioning as a hybrid prodrug of Ciprofloxacin (Cip) and hydroxybenzyl alcohol (HBA). CPBP molecules can generate nanoassemblies via self-assembly and subsequently undergo decomposition to synchronously release Cip and HBA upon hydrogen peroxide (HO) exposure. The CPBP NPs exert antibacterial and anti-inflammatory properties through the controlled release of Cip and HBA, while also facilitating the scavenging of reactive oxygen species. These CPBP NPs exhibit broad-spectrum antibacterial activity against both Gram-negative bacteria (, 98.4%) and Gram-positive bacteria (, 98.5%). Notably, CPBP NPs not only accumulate in the lungs to facilitate organ-specific infection treatment but also expedite the healing process of infected wounds. Consequently, this HO-activatable hybrid nanoprodrug, possessing excellent biocompatibility, holds substantial promise for advancing clinical applications in managing bacterial infections.
追求有效的抗菌策略，旨在减轻病原菌感染同时尽量减少耐药性，仍然至关重要。一种整合不同治疗成分的联合治疗策略可以提高整体疗效并减轻不良影响，从而在对抗细菌感染方面展现出巨大的前景。在本研究中，精心设计了一种自组装混合纳米前药（CPBP NPs），它作为环丙沙星（Cip）和羟基苯甲醇（HBA）的混合前药发挥作用。CPBP分子可通过自组装形成纳米聚集体，随后在暴露于过氧化氢（HO）时发生分解，同步释放Cip和HBA。CPBP NPs通过Cip和HBA的控释发挥抗菌和抗炎特性，同时还促进活性氧的清除。这些CPBP NPs对革兰氏阴性菌（，98.4%）和革兰氏阳性菌（，98.5%）均表现出广谱抗菌活性。值得注意的是，CPBP NPs不仅在肺部蓄积以促进器官特异性感染治疗，还加速感染伤口的愈合过程。因此，这种具有优异生物相容性的HO可激活混合纳米前药在推进细菌感染管理的临床应用方面具有巨大潜力。
