Albumin-Coated Mesoporous Polydopamine Nanoparticles for Renal Delivery of Epigallocatechin Gallate against Cisplatin-Induced Acute Kidney Injury.

Cisplatin-induced acute kidney injury (AKI) remains a serious clinical complication, with excessive reactive oxygen species (ROS) recognized as key contributors. The natural antioxidant epigallocatechin-3-gallate (EGCG) shows promise in mitigating oxidative stress-related damage. However, its clinical application is limited by poor stability and low renal bioavailability. To address this, we developed a biocompatible nanoplatform by encapsulating EGCG within mesoporous polydopamine nanoparticles (EGCG-MPDA). Ultrasmall nanoparticles (<10 nm or <20 kDa) undergo rapid glomerular filtration and renal clearance, limiting therapeutic retention. While uncoated MPDA nanoparticles (∼200 nm) are large enough to avoid renal filtration, their size renders them highly susceptible to opsonization and MPS sequestration. To address this MPS-mediated clearance, we coated MPDA with a preclinically used BSA shell to create EGCG-MPDA@BSA. The biocompatible BSA corona acts as a "stealth" layer to attenuate opsonization, reduce early hepatic sequestration, and enhance interactions with peritubular endothelial cells, promoting nanoparticle passage into injured tubular epithelial cells. In a murine cisplatin-induced AKI model, EGCG-MPDA@BSA exhibited significantly enhanced therapeutic efficacy compared to uncoated nanoparticles and free EGCG. Transcriptomic and biochemical analyses revealed that its superior therapeutic efficacy arises from the activation of the Nrf2/HO-1/GPX4 antioxidant pathway, thereby alleviating oxidative stress, inflammation, and tubular damage. Collectively, this work presents an albumin corona strategy that enables effective renal retention of large nanoparticles, offering a safe, translatable approach for localized AKI therapy.