Department of General Surgery, Chun’an First People’s Hospital (Zhejiang Provincial People's Hospital Chun’an Branch), Hangzhou 311700, China
Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou 310014, China
Curr Top Med Chem. 2020;20(27):2472-2492. doi: 10.2174/1568026620666200922113054.
Extracellular vesicles (EVs) are membrane vesicles (MVs) playing important roles in various cellular and molecular functions in cell-to-cell signaling and transmitting molecular signals to adjacent as well as distant cells. The preserved cell membrane characteristics in MVs derived from live cells, give them great potential in biological applications. EVs are nanoscale particulates secreted from living cells and play crucial roles in several important cellular functions both in physiological and pathological states. EVs are the main elements in intercellular communication in which they serve as carriers for various endogenous cargo molecules, such as RNAs, proteins, carbohydrates, and lipids. High tissue tropism capacity that can be conveniently mediated by surface molecules, such as integrins and glycans, is a unique feature of EVs that makes them interesting candidates for targeted drug delivery systems. The cell-derived giant MVs have been exploited as vehicles for delivery of various anticancer agents and imaging probes and for implementing combinational phototherapy for targeted cancer treatment. Giant MVs can efficiently encapsulate therapeutic drugs and deliver them to target cells through the membrane fusion process to synergize photodynamic/photothermal treatment under light exposure. EVs can load diagnostic or therapeutic agents using different encapsulation or conjugation methods. Moreover, to prolong the blood circulation and enhance the targeting of the loaded agents, a variety of modification strategies can be exploited. This paper reviews the EVs-based drug delivery strategies in cancer therapy. Biological, pharmacokinetics and physicochemical characteristics, isolation techniques, engineering, and drug loading strategies of EVs are discussed. The recent preclinical and clinical progresses in applications of EVs and oncolytic virus therapy based on EVs, the clinical challenges and perspectives are discussed.
细胞外囊泡(EVs)是一种膜囊泡(MVs),在细胞间信号传递和向邻近及远处细胞传递分子信号等多种细胞和分子功能中发挥着重要作用。来源于活细胞的 MVs 保留了细胞膜的特征,这使它们在生物应用中具有巨大的潜力。EVs 是从活细胞分泌的纳米级颗粒,在生理和病理状态下的几种重要细胞功能中发挥着关键作用。EVs 是细胞间通讯的主要元素,它们作为各种内源性货物分子(如 RNA、蛋白质、碳水化合物和脂质)的载体。EVs 的一个独特特征是具有高组织趋向性,这可以通过表面分子(如整合素和聚糖)方便地介导,这使它们成为靶向药物传递系统的有趣候选者。细胞衍生的巨大 MVs 已被用作递送各种抗癌剂和成像探针的载体,并用于实施组合光疗以靶向癌症治疗。巨大 MVs 可以通过膜融合过程有效地将治疗药物包裹并递送至靶细胞,以协同光动力/光热治疗在光照下。EVs 可以使用不同的封装或缀合方法来装载诊断或治疗剂。此外,为了延长血液循环时间并增强负载剂的靶向性,可以利用各种修饰策略。本文综述了基于 EVs 的癌症治疗药物传递策略。讨论了 EVs 的生物学、药代动力学和物理化学特性、分离技术、工程和药物加载策略。讨论了基于 EVs 的 EVs 和溶瘤病毒治疗的最近临床前和临床进展、临床挑战和前景。
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