![]() Numerous studies have demonstrated that released EVs tend to convey specific molecules to the parental cells, which aids EV homing. Therapeutic drugs or nucleic acid molecules are distributed to tissues or organs employing EVs as transporters when they are released into the extracellular matrix. The surface enrichment of EVs with numerous receptors or ligands that have a natural affinity for receptors heavily expressed on the surface of target cells is the method by which they are targeted. The main equipment for EVs to accomplish targeted missions is structures enriched on the surface of EVs, such as receptor-ligand proteins. It is imperative to explore its homing mission and develop solutions to improve its targeting ability. As such, if the targeting specificity can be improved further, EVs are expected to be a milestone step for covering the current shortage in targeted precision drug delivery. Researchers have used it as a novel drug delivery tool because of several properties: (1) excellent biocompatibility and low immunogenicity (2) the internal vesicle structure provides drug-carrying space and protects the internal material from degradation in circulating tissue fluid (3) the external lipid bilayer allows it to cross various tissue barriers (99% of molecules are blocked) and (4) the proteins, lipids, and glycans on the membrane surface give it homing mission and provide natural sites for artificial modifications. Due to limited isolation techniques, EVs are currently divided into microvesicles, exosomes, and other EV subgroups, which differ in size, mode of production, and contents, and we focus on the EVs targeting drug delivery systems in this review. Extracellular vesicles (EVs), 50–1000 nm nanovesicles that play roles in near and distant-range intercellular communication, are natural cargo carriers in our bodies. Although researchers have spent decades developing targeted drug delivery systems, they still face challenges such as their side effects and failure to deliver precisely on target, being blocked by tissue barriers, being eliminated by the body as a foreigner. ![]() Precision medicine poses new challenges for modern drug delivery systems, the most important of which is targeted precision delivery. This review will provide new insights into the development of precision medicine delivery systems. Furthermore, contemporary issues such as the lack of a gold standard for assessing targeting efficiency are discussed. ![]() ![]() We also highlight the auxiliary strategies to enhance specificity by changing the external environment, such as magnetic and photothermal. We then go over nanoengineering techniques that modify EVs for improving specific targeting, such as source cell alteration and modification of EVs surface. In this review, we comprehensively summarize the inherent homing mechanisms of EVs and the effects of the donor cell source and administration route on targeting specificity. Therefore, the specificity of natural EVs delivery systems urgently needs to be further improved. ![]() However, most of the natural therapeutic EVs face the fate of being cleared by macrophages, resulting in off-target. The membranes of EVs are enriched for receptors or ligands that interact with target cells, which endows them with inherent targeting mission. As such, the natural endogenous cargo delivery vehicle-extracellular vesicles (EVs)-have sparked significant interest for its unique inherent targeting properties, biocompatibility, transmembrane ability, and circulatory stability. But the large-scale applications of these systems are limited due to unsatisfactory targeting efficiency, cytotoxicity, easy removability, and instability. Inspired by techniques from biology, pharmaceutical sciences, and nanoengineering, numerous targeted drug delivery systems have been developed in recent decades. Precision medicine has put forward the proposition of "precision targeting" for modern drug delivery systems. ![]()
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