PDF(Pubmed)
Abstract：
Extracellular vesicles (EVs), characterized by low immunogenicity, high biocompatibility and targeting specificity along with excellent blood-brain barrier permeability, are increasingly recognized as promising drug delivery vehicles for treating a variety of diseases, such as cancer, inflammation and viral infection. However, recent findings demonstrate that the intracellular delivery efficiency of EVs fall short of expectations due to phagocytic clearance mediated by the host mononuclear phagocyte system through Fcγ receptors, complement receptors as well as non-opsonic phagocytic receptors. In this text, we investigate a range of bacterial virulence proteins that antagonize host phagocytic machinery, aiming to explore their potential in engineering EVs to counteract phagocytosis. Special emphasis is placed on IdeS secreted by Group A Streptococcus and ImpA secreted by Pseudomonas aeruginosa, as they not only counteract phagocytosis but also bind to highly upregulated surface biomarkers αVβ3 on cancer cells or cleave the tumor growth and metastasis-promoting factor CD44, respectively. This suggests that bacterial anti-phagocytic proteins, after decorated onto EVs using pre-loading or post-loading strategies, can not only improve EV-based drug delivery efficiency by evading host phagocytosis and thus achieve better therapeutic outcomes but also further enable an innovative synergistic EV-based cancer therapy approach by integrating both phagocytosis antagonism and cancer targeting or deactivation.
摘要：
细胞外囊泡（EV），以低免疫原性为特征，高生物相容性和靶向特异性以及优异的血脑屏障通透性，越来越被认为是治疗各种疾病的有前途的药物输送工具，比如癌症，炎症和病毒感染。然而,最近的发现表明，由于宿主单核吞噬细胞系统通过Fcγ受体介导的吞噬清除，EV的细胞内递送效率达不到预期，补体受体以及非调理吞噬受体。在本文中，我们研究了一系列拮抗宿主吞噬机制的细菌毒力蛋白，旨在探索它们在工程电动汽车中抵消吞噬作用的潜力。特别强调由A组链球菌分泌的IdeS和铜绿假单胞菌分泌的ImpA。因为它们不仅抵消吞噬作用，而且还与癌细胞上高度上调的表面生物标志物αVβ3结合，或分别切割肿瘤生长和转移促进因子CD44。这表明细菌抗吞噬蛋白，在使用预加载或后加载策略装饰到电动汽车上之后，不仅可以通过逃避宿主吞噬作用来提高基于EV的药物递送效率，从而获得更好的治疗效果，而且还可以通过整合吞噬作用拮抗作用和癌症靶向或失活来进一步实现创新的基于EV的协同癌症治疗方法。
