All cells release extracellular vesicles (EVs) as part of their normal physiology. As one of the subtypes, exosomes (EXOs) have an average size range of approximately 40 nm–160 nm in diameter. Benefiting from their inherent immunogenicity and biocompatibility, the utility of autologous EXOs has the potential for both disease diagnosis/treatment. EXOs are generally employed as “bioscaffolds” and the whole diagnostic and therapeutic effects are mainly ascribed to exogenous cargos on the EXOs, such as proteins, nucleic acids, and chemotherapeutic agents and fluorophores delivered into specific cells or tissues. Surface engineering of EXOs for cargo loadings is one of the prerequisites for EXO-mediated diagnosis/treatment. After revisiting EXO-mediated diagnosis/treatment, the most popular strategies to directly undertake loadings of exogenous cargos on EXOs include genetic and chemical engineering. Generally, genetically-engineered EXOs can be merely produced by living organisms and intrinsically face some drawbacks. However, chemical methodologies for engineered EXOs diversify cargos and extend the functions of EXOs in the diagnosis/treatment. In this review, we would like to elucidate different chemical advances on the molecular level of EXOs along with the critical design required for diagnosis/treatment. Besides, the prospects of chemical engineering on the EXOs were critically addressed. Nevertheless, the superiority of EXO-mediated diagnosis/treatment via chemical engineering remains a challenge in clinical translation and trials. Furthermore, more chemical crosslinking on the EXOs is expected to be explored. Despite substantial claims in the literature, there is currently no review to exclusively summarize the chemical engineering to EXOs for diagnosis/treatment. We envision chemical engineering of EXOs will encourage more scientists to explore more novel technologies for a wider range of biomedical applications and accelerate the successful translation of EXO-based drug “bioscaffolds” from bench to bedside.

所有细胞都会释放细胞外囊泡（EV）作为其正常生理的一部分。作为亚型之一，外泌体 (EXO) 的平均尺寸范围直径约为 40 nm–160 nm。受益于其固有的免疫原性和生物相容性，自体 EXO 的应用具有疾病诊断/治疗的潜力。EXO通常被用作“生物支架”，整个诊断和治疗效果主要归因于EXO上的外源性货物，例如递送到特定细胞或组织中的蛋白质、核酸、化疗剂和荧光团。用于装载货物的 EXO 表面工程是 EXO 介导的诊断/治疗的先决条件之一。重新审视 EXO 介导的诊断/治疗后，直接在 EXO 上装载外源货物的最流行的策略包括基因工程和化学工程。一般来说，基因工程 EXO 只能由生物体产生，本质上面临一些缺点。然而，工程 EXO 的化学方法使货物多样化并扩展了 EXO 在诊断/治疗中的功能。在这篇综述中，我们希望阐明 EXO 分子水平上的不同化学进展以及诊断/治疗所需的关键设计。此外，EXO 化学工程的前景也受到了批判性的讨论。然而，通过化学工程介导的 EXO 介导的诊断/治疗的优越性仍然是临床转化和试验中的挑战。此外，预计将探索 EXO 上更多的化学交联。尽管文献中有大量主张，但目前还没有专门总结用于诊断/治疗的 EXO 化学工程的综述。我们预计 EXO 的化学工程将鼓励更多的科学家为更广泛的生物医学应用探索更多新技术，并加速基于 EXO 的药物“生物支架”从实验室到临床的成功转化。