On-demand pH-sensitive surface charge-switchable polymeric micelles for targeting Pseudomonas aeruginosa biofilms development.
On-demand pH-sensitive surface charge-switchable polymeric micelles for targeting Pseudomonas aeruginosa biofilms development.
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DOI：
10.1186/s12951-021-00845-0
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发表时间：
2021-04-09
影响因子：
10.2
通讯作者：
Hong W
中科院分区：
文献类型：
--
作者：
Chen X;Guo R;Wang C;Li K;Jiang X;He H;Hong W
细菌生物被膜是一个复杂的临床问题，常导致细菌产生耐药性，降低抗生素的治疗效果。尽管胶束在生物膜处理中的应用已引起人们的关注，但胶束在生物膜中的有效渗透和截留仍然面临着很大的挑战。在这项研究中，我们制造了按需pH敏感的表面电荷可切换的阿奇霉素（AZM）包封胶束（表示为AZM-SCSMs），旨在作为治疗剂治疗铜绿假单胞菌（P. aeruginosa）生物膜。AZM-SCSM由聚（1-丙交酯）-聚醚酰亚胺-羟基-甲氧基聚乙二醇（PLA-PEI-hyd-mPEG）组成。值得注意的是，pH敏感的酰腙键可以在酸性生物膜微环境中断裂，释放基于PLA-PEI的二次AZM负载阳离子胶束（AZM-SCMs），而不破坏胶束的完整性，这可以通过静电吸引利用胶束来定制药物-细菌相互作用。结果表明，AZM-SCMs带正电荷，能增强药物在生物膜内的渗透和滞留，提高药物与细菌膜的结合力，增加药物的内化，是一种潜在的抗生物膜药物。AZM-SCSM的优异的体内治疗性能通过靶向递送至感染组织并在携带肿瘤的小鼠模型中降低细菌负荷来证实。本研究不仅为构建非解聚pH敏感的SCSMs提供了一种新的方法，而且为生物膜相关感染的治疗提供了一种有效的手段。在线版本包含补充材料，可通过10.1186/s12951-021-00845-0获得。
Bacterial biofilm is the complicated clinical issues, which usually results in bacterial resistance and reduce the therapeutic efficacy of antibiotics. Although micelles have been drawn attention in treatment of the biofilms, the micelles effectively permeate and retain in biofilms still facing a big challenge. In this study, we fabricated on-demand pH-sensitive surface charge-switchable azithromycin (AZM)-encapsulated micelles (denoted as AZM-SCSMs), aiming to act as therapeutic agent for treating Pseudomonas aeruginosa (P. aeruginosa) biofilms. The AZM-SCSMs was composed of poly(l-lactide)-polyetherimide-hyd-methoxy polyethylene glycol (PLA-PEI-hyd-mPEG). It was noteworthy that the pH-sensitive acylhydrazone bond could be cleaved in acidic biofilm microenvironment, releasing the secondary AZM-loaded cationic micelles based on PLA-PEI (AZM-SCMs) without destroying the micellar integrity, which could tailor drug-bacterium interaction using micelles through electrostatic attraction. The results proved that positively charged AZM-SCMs could facilitate the enhanced penetration and retention inside biofilms, improved binding affinity with bacterial membrane, and added drug internalization, thus characterized as potential anti-biofilm agent. The excellent in vivo therapeutic performance of AZM-SCSMs was confirmed by the targeting delivery to the infected tissue and reduced bacterial burden in the abscess-bearing mice model. This study not only developed a novel method for construction non-depolymerized pH-sensitive SCSMs, but also provided an effective means for the treatment of biofilm-related infections. The online version contains supplementary material available at 10.1186/s12951-021-00845-0.
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