文献类型： 外文期刊

作者： Zhou, Yuqin ¹ ; Du, Shihan ¹ ; He, Kailun ² ; Zhou, Beilei ² ; Chen, Zixuan ³ ; Zheng, Cheng ² ; Zhou, Minghao ² ; Li, Jue ² ; Chen, Yue ² ; Zhang, Hu ⁴ ; Yuan, Hong ⁵ ; Li, Yinghong ² ; Chen, Yan ⁶ ; Hu, Fuqiang ⁵ ;

作者机构： 1.China Pharmaceut Univ, Sch Pharm, 639 Longmian Ave, Nanjing 211198, Peoples R China

2.Zhejiang Inst Food & Drug Control, NMPA Key Lab Testing & Warning Pharmaceut, Zhejiang Key Lab Biopharmaceut Contact Mat, 325 Pingle St, Hangzhou 310052, Peoples R China

3.Hangzhou Med Coll, Sch Pharmaceut Sci, Hangzhou 311399, Peoples R China

4.Zhejiang Acad Agr Sci, Inst Agroprod Safety & Nutr, 198 Shiqiao Rd, Hangzhou 310021, Peoples R China

5.Zhejiang Univ, Coll Pharmaceut Sci, 866 Yuhangtang Rd, Hangzhou 310058, Peoples R China

6.Zhejiang Univ, Sir Run Run Shaw Hosp, Sch Med, Dept Infect Dis, Hangzhou 310016, Peoples R China

关键词： daptomycin; M1-type macrophage membrane; Staphylococcus aureus; drug-resistance; zebrafish

期刊名称：PHARMACEUTICALS （ 影响因子：4.8； 五年影响因子：4.9 ）

ISSN：

年卷期： 2025 年 18 卷 8 期

页码：

收录情况： SCI

摘要： Background/Objective: Staphylococcus aureus (S. aureus) is a clinically significant pathogenic bacterium. Daptomycin (DAP) is a cyclic lipopeptide antibiotic used to treat infections caused by multidrug-resistant Gram-positive bacteria, including S. aureus. However, DAP currently faces clinical limitations due to its short half-life, toxic side effects, and increasingly severe drug resistance issues. This study aimed to develop a biomimetic nano-drug delivery system to enhance targeting ability, prolong blood circulation, and mitigate resistance of DAP. Methods: DAP-loaded chitosan nanocomposite particles (DAP-CS) were prepared by electrostatic self-assembly. Macrophage membrane vesicles (MM) were prepared by fusion of M1-type macrophage membranes with 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC). A biomimetic nano-drug delivery system (DAP-CS@MM) was constructed by the coextrusion process of DAP-CS and MM. Key physicochemical parameters, including particle diameter, zeta potential, encapsulation efficiency, and membrane protein retention, were systematically characterized. In vitro immune escape studies and in vivo zebrafish infection models were employed to assess the ability of immune escape and antibacterial performance, respectively. Results: The particle size of DAP-CS@MM was 110.9 +/- 13.72 nm, with zeta potential +11.90 +/- 1.90 mV, and encapsulation efficiency 70.43 +/- 1.29%. DAP-CS@MM retained macrophage membrane proteins, including functional TLR2 receptors. In vitro immune escape assays, DAP-CS@MM demonstrated significantly enhanced immune escape compared with DAP-CS (p < 0.05). In the zebrafish infection model, DAP-CS@MM showed superior antibacterial efficacy over both DAP and DAP-CS (p < 0.05). Conclusions: The DAP-CS@MM biomimetic nano-drug delivery system exhibits excellent immune evasion and antibacterial performance, offering a novel strategy to overcome the clinical limitations of DAP.