Exosomes: emerging biomarkers and therapeutic potential in postoperative delirium and postoperative cognitive...

Postoperative delirium (POD) and postoperative cognitive dysfunction (POCD) are common and clinically significant perioperative neurocognitive disorders that disproportionately affect elderly surgical patients. Despite their substantial impact on postoperative recovery and long-term outcomes, the lack of validated biomarkers and effective targeted therapies remains a major challenge in perioperative medicine.

Owing to their intrinsic ability to cross the blood-brain barrier and stably encapsulate central nervous system-derived biomolecules, exosomes have emerged as promising candidates for non-invasive biomarker discovery in POD and POCD. Disease-associated alterations in exosomal cargo, encompassing proteins such as P-tau and Aβ1-42, nucleic acids including miR-584-5p and circRNA_089763, and lipid-associated constituents, provide valuable molecular signatures for early diagnosis, disease stratification, prognostic assessment, and dynamic monitoring of perioperative neurocognitive disorders. It should be noted, however,that the majority of current evidence is extrapolated from Alzheimer's disease and other neurodegenerative conditions rather than directly validated in POD and POCD cohorts, and dedicated prospective studies remain warranted.

Exosomes exert therapeutic effects through two complementary mechanisms: serving as vehicles for targeted drug delivery and acting as endogenous neuroprotective mediators. Their excellent biocompatibility,low immunogenicity, and inherent capacity to traverse the blood-brain barrier render them attractive platforms for attenuating neuroinflammation, promoting synaptic repair, enhancing neurogenesis, and restoring blood-brain barrier integrity.

Despite their considerable promise, several challenges continue to impede clinical translation, including limitations in large-scale production, the lack of standardized isolation and characterization protocols, biological heterogeneity, and regulatory barriers. Future research should focus on establishing POD/POCD-specific exosomal biomarker panels, developing GMP-compliant manufacturing systems, engineering precision-targeted exosomal therapeutics, and conducting rigorous multicenter clinical studies to validate their safety and efficacy.

Exosomes hold substantial promise for transforming the diagnosis and treatment of POD and POCD. With continued advances in engineering technologies, mechanistic understanding, and clinical validation, exosome-based diagnostic and therapeutic strategies are expected to become an integral component of precision perioperative medicine.