College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, Tallahassee, FL 32307, USA.
Department of Biomedical Sciences, College of Medicine, Florida State University, Tallahassee, FL 32306, USA.
Crit Rev Ther Drug Carrier Syst. 2021;38(5):53-97. doi: 10.1615/CritRevTherDrugCarrierSyst.2021036301.
Exosomes are endogenous extracellular vesicles (30-100 nm) composed with membrane lipid bilayer which carry vesicular proteins, enzymes, mRNA, miRNA and nucleic acids. They act as messengers for intra- and inter-cellular communication. In addition to their physiological roles, exosomes have the potential to encapsulate and deliver small chemotherapeutic drugs and biological molecules such as proteins and nucleic acid-based drugs to the recipient tissue or organs. Due to their biological properties, exosomes have better organotropism, homing capacity, cellular uptake and cargo release ability than other synthetic nano-drug carriers such as liposomes, micelles and nanogels. The secretion of tumor-derived exosomes is increased in the hypoxic and acidic tumor microenvironment, which can be used as a target for nontoxic and nonimmunogenic drug delivery vehicles for various cancers. Moreover, exosomes have the potential to carry both hydrophilic and hydrophobic chemotherapeutic drugs, bypass RES effect and bypass BBB. Exosomes can be isolated from other types of EVs and cell debris based on their size, density and specific surface proteins through ultracentrifugation, density gradient separation, precipitation, immunoaffinity interaction and gel filtration. Drugs can be loaded into exosomes at the biogenesis stage or with the isolated exosomes by incubation, electroporation, extrusion or sonication methods. Finally, exosomal cargo vehicles can be characterized by ultrastructural microscopic analysis. In this review we intend to summarize the inception, structure and function of the exosomes, role of exosomes in immunological regulation and cancer, methods of isolation and characterization of exosomes and products under clinical trials. This review will provide an inclusive insight of exosomes in drug delivery.
外泌体是由膜脂质双层组成的内源性细胞外囊泡（30-100nm），携带囊泡蛋白、酶、mRNA、miRNA 和核酸。它们充当细胞内和细胞间通讯的信使。除了发挥生理作用外，外泌体还有潜力封装和递送至受体组织或器官的小分子化疗药物和生物分子，如蛋白质和基于核酸的药物。由于其生物学特性，外泌体比其他合成纳米药物载体（如脂质体、胶束和纳米凝胶）具有更好的器官趋向性、归巢能力、细胞摄取能力和货物释放能力。肿瘤来源的外泌体在低氧和酸性肿瘤微环境中的分泌增加，可作为各种癌症的无毒和非免疫原性药物递送载体的靶点。此外，外泌体具有携带亲水性和疏水性化疗药物的潜力，可以绕过 RES 效应和 BBB。可以通过超速离心、密度梯度分离、沉淀、免疫亲和相互作用和凝胶过滤等方法，根据其大小、密度和特定表面蛋白，从其他类型的 EV 和细胞碎片中分离出外泌体。可以在生物发生阶段或通过孵育、电穿孔、挤出或超声处理将药物加载到外泌体中。最后，可以通过超微结构分析对外泌体货物载体进行表征。在这篇综述中，我们旨在总结外泌体的起源、结构和功能、外泌体在免疫调节和癌症中的作用、外泌体的分离和表征方法以及临床试验中的产品。这篇综述将提供对外泌体在药物递送中应用的全面了解。
