纳米药物载体用于治疗胞内菌感染的研究进展

doi:10.11949/0438-1157.20231326

摘要/Abstract

摘要：

胞内菌能够逃避机体免疫并在宿主细胞内正常生长繁殖，比起胞外细菌更难清除，容易造成较为严重的感染。传统的抗生素治疗，药物无法突破宿主细胞膜的屏障，并且容易引起较强的毒副作用和多药耐药性。优良的纳米载体具有良好的生物相容性且易于修饰，有望通过构建纳米药物递送系统增强抗菌药物的细胞膜穿透性和胞内菌靶向性，在治疗胞内菌感染上具有巨大潜力和广阔前景。介绍了目前可用于治疗胞内菌感染的各种纳米颗粒，归纳总结了增强纳米药物递送系统治疗效果的机制和方法，阐述了目前在使用纳米药物递送系统治疗胞内菌感染时仍存在的问题，以期为构建更优良的纳米药物递送系统治疗胞内菌感染提供启发。

关键词: 纳米载体, 胞内菌, 细菌靶向, 抗菌策略

Abstract:

Intracellular bacteria can escape the body's immunity and grow and reproduce normally in the host cell, which are more difficult to remove than extracellular bacteria and can easily cause more serious infections. With traditional antibiotic treatment, the drugs cannot break through the host cell membrane barrier and can easily cause strong toxic side effects and multidrug resistance. Excellent nanocarriers have good biocompatibility and are easy to modify, which is expected to enhance membrane penetration and bacterial targeting of antibacterial drugs through the construction of nanodelivery systems, offering great potential and broad prospects in the treatment of intracellular bacterial infections. This paper introduces various nanoparticles that can be used to treat intracellular bacterial infections, summarizes the mechanisms and methods for enhancing the therapeutic effects of drug nanodelivery systems, and elaborates on the problems that still exist when using nano-drug delivery systems to treat intracellular bacterial infections, in order to provide inspiration for the construction of better drug delivery systems to treat intracellular bacterial infections.

Key words: nanocarriers, intracellular bacteria, bacterial targeting, antibacterial strategy

中图分类号:

TQ 469

巨晓洁, 宋婉璐, 周宸宇, 沈秋彤, 廖雨田, 龚珏颖, 褚良银. 纳米药物载体用于治疗胞内菌感染的研究进展[J]. 化工学报, 2024, 75(4): 1153-1166.

Xiaojie JU, Wanlu SONG, Chenyu ZHOU, Qiutong SHEN, Yutian LIAO, Jueying GONG, Liangyin CHU. Advances in drug nanodelivery systems for the treatment of intracellular bacterial infections[J]. CIESC Journal, 2024, 75(4): 1153-1166.

图/表 5

图1 常见纳米药物递送系统示意图

Fig.1 Schematic illustrations of common drug nanodelivery systems

表1 用于胞内菌治疗的纳米药物递送系统

Table 1 Nanodelivery systems for intracellular bacteria therapy

类型	优点	缺点	典型体系	杀菌率
聚合物纳米颗粒	稳定性高；易修饰	少部分具有细胞毒性；溶剂残留	天然聚合物纳米颗粒、合成聚合物纳米颗粒^[13]	高^{[15, 48-52]}
生物源性纳米颗粒	生物相容性良好；可降解；靶向性好	稳定性较差	外泌体、细胞膜纳米颗粒、细菌囊泡^[17]	极高^{[23, 53-54]}
脂质体与脂质纳米颗粒	生物相容性良好；不良反应少；易制备；靶向性强	SLN载药量低	脂质体、SLN、NLC^[29]	极高^{[26, 31, 55-56]}
无机纳米颗粒	形状多样；易制备；易修饰	可降解性较差	金属和金属氧化物纳米颗粒、量子点、无机非金属纳米颗粒^[32]	高^{[46-47, 57-58]}

图2 (a) 抗生素治疗胞内菌感染的挑战[60]；(b) 增强感染细胞对药物的内化机制[7]

Fig.2 (a) Challenges in the antibiotic treatment of intracellular bacterial infections[60]; (b) Enhancement of internalization mechanisms of drugs by infected cells[7]

图3 (a) 治疗胞内金黄色葡萄球菌感染的纳米药物递送系统制备示意图[83]；(b) AAC作用机理示意图[94]；(c) ZnO@MSNs-DOX合成示意图及响应pH释放药物过程[96]；(d) 磁性MSNs释放机制图[98]

Fig.3 (a) Schematic diagram of preparation of drug nanodelivery system for the treatment of intracellular Staphylococcus aureus infection[83]; (b) Schematic diagram of the action mechanism of AAC[94]; (c) Schematic diagram of synthesis and pH-responsive drug release process of ZnO@MSNs-DOX[96]; (d) Schematic diagram of the release mechanism of magnetic MSNs[98]

图4 (a)聚合物纳米颗粒pH敏感释放万古霉素示意图[103]；(b)Ag@QAL的合成路线及抗菌过程示意图[109]

Fig.4 (a) Schematic diagram of pH-sensitive release of vancomycin from polymer nanoparticles[103]; (b) Schematic diagram of the synthesis route and antibacterial process of Ag@QAL[109]

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