Engineered Exosomes: Advances in Therapeutic Applications for OtolaryngologyHead and Neck Diseases

Han Zhu, Jing He, Shishi Yang, Gang Qin Department of Otolaryngology Head and Neck Surgery, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of ChinaThese authors contributed equally to this workCorrespondence: Gang Qin, Email qingₗzmc@163. comAbstract: Given the intricate anatomy of otolaryngology–head and neck (OHNS) regions and the inherent limitations of conventional therapies, many OHNS diseases have suboptimal clinical outcomes. As natural intercellular mediators, exosomes have demonstrated unique application potential in OHNS treatment in recent years, thanks to their high biocompatibility, low immunogenicity, and intrinsic targeting capabilities. However, such issues as limited drug-loading capacity, suboptimal in vivo stability, and insufficient targeting precision still hinder their clinical translation. Notably, recent advances in engineering strategies such as genetic editing, surface modification, and optimized drug loading enhance natural exosomes’ functionality, boosting targeting accuracy, in vivo stability, and therapeutic efficacy. Considering conventional therapy limitations and engineered exosomes’ unique potential, this review synthesizes their progress, mechanisms, and translational challenges in OHNS, and addresses lingering technical and translation barriers via interdisciplinary collaboration to optimize their design, utility, and bench-to-bedside translation, as these exosomes are promising precision tools for refractory OHNS diseases advancing precision medicine in the field. Keywords: engineered exosomes, otorhinolaryngological tumors, inflammatory diseases, tissue regeneration and repair, targeted delivery