Exosomes as Targeted Drug Delivery Systems: Strategies and Mechanisms for Mitigating Cisplatin-Induced Hair Cell Damage

Abstract

Cisplatin is a highly effective chemotherapeutic agent widely used for various solid tumors; however, its clinical utility is severely compromised by cisplatin-induced ototoxicity (CIO), which leads to permanent sensorineural hearing loss. The primary pathological hallmark of CIO is the irreversible damage and loss of auditory hair cells, driven by mechanisms including oxidative stress, DNA damage, and inflammatory cascades. Despite numerous candidates for otoprotection, efficient delivery to the inner ear remains a significant challenge due to the blood-labyrinth barrier (BLB) and the risk of systemic side effects. Recently, exosomes—small extracellular vesicles—have emerged as a promising bio-inspired drug delivery system (DDS) for inner ear therapy. Due to their low immunogenicity, high biocompatibility, and innate ability to cross biological barriers, exosomes offer a revolutionary platform for the targeted delivery of therapeutic agents. This review systematically delineates the molecular mechanisms of cisplatin-induced hair cell damage and highlights the recent advances in utilizing exosome-encapsulated drugs, including small molecules, nucleic acids, and proteins for otoprotection. We further discuss innovative strategies for exosome engineering, such as surface modification and active loading techniques, to enhance their targeting precision and therapeutic efficacy within the cochlea. Finally, the challenges of clinical translation and future perspectives of exosome-based nanomedicine in hearing preservation are addressed, providing a theoretical framework for the development of next-generation otoprotective strategies.