School of Pharmaceutical Sciences (Shenzhen), Shenzhen Campus of Sun Yat-sen University, Shenzhen 518107, PR China.
Institute of Infectious Diseases, Shenzhen Bay Laboratory, Shenzhen 518132, PR China.
Sci Adv. 2024 Apr 5;10(14):eadk9754. doi: 10.1126/sciadv.adk9754.
The lack of bacterial-targeting function in antibiotics and their prophylactic usage have caused overuse of antibiotics, which lead to antibiotic resistance and inevitable long-term toxicity. To overcome these issues, we develop neutrophil-bacterial hybrid cell membrane vesicle (HMV)-coated biofunctional lipid nanoparticles (LNP@HMVs), which are designed to transport antibiotics specifically to bacterial cells at the infection site for the effective treatment and prophylaxis of bacterial infection. The dual targeting ability of HMVs to inflammatory vascular endothelial cells and homologous Gram-negative bacterial cells results in targeted accumulation of LNP@HMVs in the site of infections. LNP@HMVs loaded with the antibiotic norfloxacin not only exhibit enhanced activity against planktonic bacteria and bacterial biofilms in vitro but also achieve potent therapeutic efficacy in treating both systemic infection and lung infection. Furthermore, LNP@HMVs trigger the activation of specific humoral and cellular immunity to prevent bacterial infection. Together, LNP@HMVs provide a promising strategy to effectively treat and prevent bacterial infection.
抗生素缺乏靶向细菌的功能及其预防性使用导致了抗生素的过度使用，从而导致了抗生素耐药性和不可避免的长期毒性。为了克服这些问题，我们开发了中性粒细胞-细菌混合细胞膜囊泡（HMV）包被的生物功能脂质纳米颗粒（LNP@HMVs），旨在将抗生素特异性递送到感染部位的细菌细胞，以有效治疗和预防细菌感染。HMV 对炎症性血管内皮细胞和同源革兰氏阴性细菌细胞的双重靶向能力导致 LNP@HMVs 在感染部位的靶向积累。负载抗生素诺氟沙星的 LNP@HMVs 不仅在体外显示出对浮游细菌和细菌生物膜的增强活性，而且在治疗全身感染和肺部感染方面也具有强大的治疗效果。此外，LNP@HMVs 触发针对特定体液和细胞免疫的激活，以预防细菌感染。总之，LNP@HMVs 提供了一种有前途的策略，可以有效治疗和预防细菌感染。
