Microneedle-Enabled Exosome Therapy: From Tumor Targeting to Precision Treatment of Complex Diseases.

Exosomes are nanoscale extracellular vesicles (EVs) that mediate intercellular communication by transporting proteins, lipids and nucleic acids. Their biocompatibility, low immunogenicity and intrinsic ability to protect labile cargo make them attractive therapeutic carriers. Yet their clinical translation remains constrained by heterogeneous isolation protocols, variable product purity, inefficient cargo loading, rapid systemic clearance and limited tissue-selective delivery. Engineering strategies, including parental-cell preconditioning, genetic modification, post-isolation cargo loading and surface functionalization, have improved the potency and targeting of exosome-based therapeutics but have not fully solved delivery-related bottlenecks. Microneedle (MN) systems provide a complementary solution by breaching the stratum corneum in a minimally invasive manner and depositing exosomes directly within defined tissue compartments. When integrated with dissolving, hydrogel, cryogenic, core-shell, Janus, threaded or stimulus-responsive MN architectures, exosomes can be retained locally, released in a programmed manner and protected from rapid degradation. This Review first summarizes the biological basis, source-dependent functions and engineering strategies of exosomes, and then outlines the design principles of MN platforms relevant to vesicle delivery. On this basis, we discuss representative studies in which MN systems have been explored to improve the local retention, controlled release and tissue-specific delivery of exosomes in cancer, wound repair, neurological injury, cardiovascular disease, immune-mediated disorders and other regenerative settings. We further summarize the translational barriers that remain for this emerging strategy, including vesicle characterization, potency assays, sterility control, scalable manufacturing, long-term safety, storage stability and batch-to-batch reproducibility.