Extracellular vesicles (EVs) have increasingly been recognized as important cell surrogates influencing many pathophysiological processes, including cellular homeostasis, cancer progression, neurologic disease, and infectious disease. These behaviors enable EVs broad application prospects for clinical application in disease diagnosis and treatment. Many studies suggest that EVs are superior to conventional synthetic carriers in terms of drug delivery and circulating biomarkers for early disease diagnosis, opening up new frontiers for modern theranostics. Despite these clinical potential, EVs containing diverse cellular components, such as nucleic acids, proteins, and metabolites are highly heterogeneous and small size. The limitation of preparatory, engineering and analytical technologies for EVs poses technical barriers to clinical translation. This article aims at present a critical overview of emerging technologies in EVs field for biomedical applications and challenges involved in their clinic translations. The current methods for isolation and identification of EVs are discussed. Additionally, engineering strategies developed to enhance scalable production and improved cargo loading as well as tumor targeting are presented. The superior clinical potential of EVs, particularly in terms of different cell origins and their application in the next generation of diagnostic and treatment platforms, are clarified.

Pathogenic gut microbiota is responsible for a few debilitating gastrointestinal diseases. While the host immune cells do produce extracellular vesicles to counteract some deleterious effects of the microbiota, the extracellular vesicles are of insufficient doses and at unreliable exposure times. Here we use mechanical stimulation of hydrogel-embedded macrophage in a bioelectronic controller that on demand boost production of up to 20 times of therapeutic extracellular vesicles to ameliorate the microbes’ deleterious effects in vivo. Our miniaturized wireless bioelectronic system termed inducible mechanical activation for in-situ and sustainable generating extracellular vesicles (iMASSAGE), leverages on wireless electronics and responsive hydrogel to impose mechanical forces on macrophages to produce extracellular vesicles that rectify gut microbiome dysbiosis and ameliorate colitis. This in vivo controllable extracellular vesicles-produced system holds promise as platform to treat various other diseases.

Extracellular vesicles (EVs) are membrane nanoarchitectures generated by cells that carry a variety of biomolecules, including DNA, RNA, proteins and metabolites. These characteristics make them attractive as circulating bioinformatic nanocabinets for liquid biopsy. Recent advances on EV biology and biogenesis demonstrate that EVs serve as highly important cellular surrogates involved in a wide range of diseases, opening up new frontiers for modern diagnostics. However, inefficient methods for EV enrichment, as well as low sensitivity of EV bioinformatic decoding technologies, hinder the use of EV nanocabinet for clinical diagnosis. To overcome these challenges, new EV nanotechnology is being actively developed to promote the clinical translation of EV diagnostics. This article aims to present the emerging enrichment strategies and bioinformatic decoding platforms for EV analysis, and their applications as bioinformatic nanomaterials in clinical settings.