Activated platelet membrane vesicles for broad-spectrum bacterial pulmonary infections management

IF 10.5 1区 医学 Q1 CHEMISTRY, MULTIDISCIPLINARY
Anqi Wei , Tianhao Ding , Guanghui Li , Feng Pan , Kaisong Tian , Ziwei Sun , Mengyuan Liu , Yinyu Ma , Zhiwei Guo , Yifei Yu , Changyou Zhan , Zui Zhang , Ye Zhu , Xiaoli Wei
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Abstract

The development of new antibiotics has lagged behind the rapid evolution of bacterial resistance, prompting the exploration of alternative antimicrobial strategies. Host-directed therapy (HDT) has emerged as a promising approach by harnessing innate immune system's natural defense mechanisms, which reduces reliance on antibiotics, and mitigates the development of resistance. Building on the important role of platelets in host immunity, activated platelet membrane vesicles (PLTv) are developed here as a host-directed therapy for broad-spectrum antibacterial infection management, leveraging several key mechanisms of action. PLTv neutralizes bacterial toxins, thereby reducing cytotoxicity. The presence of platelet receptors on PLTv enables them to act as decoys, binding bacteria through receptor interactions and facilitating their phagocytosis by neutrophils and macrophages. Additionally, PLTv bound to bacteria promote the formation of neutrophil extracellular traps (NETs), enhancing the immune system's ability to trap and kill bacteria. In mouse models of pulmonary infections caused by the Methicillin-resistant Staphylococcus aureus, P. aeruginosa, and A. baumannii, administration of PLTv significantly reduces bacterial counts in the lungs and protects against mortality. Taken together, the present work highlights PLTv as a promising host-directed therapy for combating broad-spectrum pulmonary drug-resistant bacterial infections, leveraging their ability to neutralize toxins, act as decoys, promote phagocytosis, and facilitate NETs formation.

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来源期刊
Journal of Controlled Release
Journal of Controlled Release 医学-化学综合
CiteScore
18.50
自引率
5.60%
发文量
700
审稿时长
39 days
期刊介绍: The Journal of Controlled Release (JCR) proudly serves as the Official Journal of the Controlled Release Society and the Japan Society of Drug Delivery System. Dedicated to the broad field of delivery science and technology, JCR publishes high-quality research articles covering drug delivery systems and all facets of formulations. This includes the physicochemical and biological properties of drugs, design and characterization of dosage forms, release mechanisms, in vivo testing, and formulation research and development across pharmaceutical, diagnostic, agricultural, environmental, cosmetic, and food industries. Priority is given to manuscripts that contribute to the fundamental understanding of principles or demonstrate the advantages of novel technologies in terms of safety and efficacy over current clinical standards. JCR strives to be a leading platform for advancements in delivery science and technology.
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