Cell-generated extracellular vesicles (EVs) are being engineered as biologically-inspired vehicles for targeted delivery of therapeutic agents to treat difficult-to-manage human diseases, including lysosomal storage disorders (LSDs). Engineered EVs offer distinct advantages for targeted delivery of therapeutics compared to existing synthetic and semi-synthetic nanoscale systems, for example with regard to their biocompatibility, circulation lifetime, efficiencies in delivery of drugs and biologics to target cells, and clearance from the body. Here, we review literature related to the design and preparation of EVs as therapeutic carriers for targeted delivery and therapy of drugs and biologics with a focus on LSDs. First, we introduce the basic pathophysiology of LDSs and summarize current approaches to diagnose and treat LSDs. Second, we will provide specific details about EVs, including subtypes, biogenesis, biological properties and their potential to treat LSDs. Third, we review state-of-the-art approaches to engineer EVs for treatments of LSDs. Finally, we summarize explorative basic research and applied applications of engineered EVs for LSDs, and highlight current challenges, and new directions in developing EV-based therapies and their potential impact on clinical medicine.

细胞产生的细胞外囊泡 (EV) 正在被设计成受生物学启发的载体，用于靶向递送治疗剂，以治疗难以控制的人类疾病，包括溶酶体贮积症 (LSD)。与现有的合成和半合成纳米级系统相比，工程 EV 在靶向治疗方面具有明显的优势，例如在生物相容性、循环寿命、将药物和生物制剂输送到靶细胞的效率以及从体内清除方面。在这里，我们回顾了与 EV 的设计和制备相关的文献，这些 EV 作为治疗载体用于药物和生物制剂的靶向递送和治疗，重点是 LSD。首先，我们介绍了 LDS 的基本病理生理学，并总结了目前诊断和治疗 LSD 的方法。第二，我们将提供有关 EV 的具体细节，包括亚型、生物发生、生物学特性及其治疗 LSD 的潜力。第三，我们回顾了设计 EV 以治疗 LSD 的最先进方法。最后，我们总结了用于 LSD 的工程 EV 的探索性基础研究和应用，并强调了当前的挑战和开发基于 EV 的疗法的新方向及其对临床医学的潜在影响。