Emerging chemical engineering of exosomes as "bioscaffolds" in diagnostics and therapeutics

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.