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蛋白质冠介导的脂质体药物递送用于细菌感染管理。

Protein corona mediated liposomal drug delivery for bacterial infection management.

作者信息

Shao Qianwen, Ding Tianhao, Pan Feng, Li Guanghui, Shen Shun, Qian Jun, Zhan Changyou, Wei Xiaoli

机构信息

School of Pharmacy & Department of Pharmacology, School of Basic Medical Sciences, Fudan University, Shanghai 201203, China.

Department of Pharmacy, Jing'an District Central Hospital of Shanghai, Shanghai 200040, China.

出版信息

Asian J Pharm Sci. 2022 Nov;17(6):855-866. doi: 10.1016/j.ajps.2022.10.003. Epub 2022 Nov 5.

Abstract

Liposomes have been widely investigated as a class of promising antibiotic delivery systems for the treatment of life-threatening bacterial infections. However, the inevitable formation of protein corona on the liposomal surface can heavily impact performance. A better understanding of the effects of protein corona on liposomal behavior can significantly improve antibacterial liposomal drug development. Here, the critical role of protein corona in mediating liposome-bacteria interactions was elucidated. Adsorption of negatively charged protein on cationic liposome weakened electrostatic attraction-enhanced liposomal binding to the bacteria. Cumulative complement deposition on anionic liposome composed of phosphatidylglycerol (DSPG sLip) contributed to a superior binding affinity of DSPG sLip to planktonic bacteria and biofilms, which was exploited to enhance bacteria-targeted drug delivery. In both -related osteomyelitis and pneumonia mice models, DSPG sLip was demonstrated as a promising antibiotic nanocarrier for managing MRSA infection, indicating the benefits of lipid composition-based protein corona modulation in liposomal antibiotic delivery for bacterial infection treatment.

摘要

脂质体作为一类用于治疗危及生命的细菌感染的有前景的抗生素递送系统,已受到广泛研究。然而,脂质体表面不可避免地形成蛋白质冠层会严重影响其性能。更好地理解蛋白质冠层对脂质体行为的影响可以显著改善抗菌脂质体药物的开发。在此,阐明了蛋白质冠层在介导脂质体与细菌相互作用中的关键作用。带负电荷的蛋白质在阳离子脂质体上的吸附减弱了静电吸引力,增强了脂质体与细菌的结合。由磷脂酰甘油组成的阴离子脂质体(DSPG sLip)上的累积补体沉积有助于DSPG sLip对浮游细菌和生物膜具有更高的结合亲和力,这被用于增强细菌靶向药物递送。在相关的骨髓炎和肺炎小鼠模型中,DSPG sLip被证明是一种用于治疗耐甲氧西林金黄色葡萄球菌(MRSA)感染的有前景的抗生素纳米载体,表明基于脂质组成的蛋白质冠层调节在脂质体抗生素递送治疗细菌感染中的益处。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c36/9800951/fe75c394fbe7/ga1.jpg

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