Brain peptides modified exosome-mediated drug delivery system for adriamycin-induced nephropathy treatment

Mitigation of adriamycin (ADR)-induced nephropathy remains a significant challenge in clinical management. Brain-targeted administration of losartan demonstrates comparable nephroprotective effects at a 1:500 concentration relative to gavage administration. This study established an exosome-based nano-delivery platform (ExoACP) to reduce drug dosage for alleviating ADR-induced nephropathy. The platform was rigorously tested for toxicity and blood-brain barrier penetration. Additionally, the role and possible mechanism of ExoACP-Los in alleviating ADR-induced nephropathy in mice were investigated. ExoACP showed enhanced penetration in brain microvascular endothelial cells, with a 7.20-fold increase in uptake. In the ADR model, ExoACP-Los exhibited anti-inflammatory and anti-fibrotic effects by downregulating the renin-angiotensin system, reducing extracellular matrix deposition by nearly half. These findings suggest ExoACP-Los can alleviate ADR-induced nephropathy by enhancing targeted drug delivery to the brain while reducing losartan. Overall, ExoACP holds significant potential for future clinical applications in chronic nephropathy.