Targeting acute kidney injury via inflammation-directed homing using emodin/vitamin E-loaded macrophage membrane-biomimetic nanovesicles.

Abstract

Acute kidney injury (AKI) is a severe complication in hospitalized patients, with ferroptosis playing a critical role in its pathogenesis, characterized by excessive oxidative stress and exaggerated inflammation. Despite its high mortality, no specific pharmacotherapy is currently available. To address this challenge, we engineered a macrophage membrane‑based biomimetic nanovesicle system (Emo/VE‑mcNVs) for targeted co‑delivery of emodin and vitamin E. By exploiting the injury‑guided homing capability of macrophages, the nanovesicles were fabricated through camouflaging emodin/vitamin E‑coloaded liposomes (Emo/VE‑LPs) with macrophage membranes. This design conferred enhanced biocompatibility, reduced macrophage uptake, immune evasion, and inflammatory tropism, enabling targeted drug delivery to injured kidneys. Cellular studies demonstrated that Emo/VE‑mcNVs were efficiently internalized by renal tubular epithelial cells (HK‑2) and markedly relieved cisplatin‑induced oxidative stress, ferroptosis, and inflammatory responses. In a murine AKI model, intravenous administration of Emo/VE‑mcNVs resulted in pronounced renal accumulation, significantly reduced serum creatinine and blood urea nitrogen levels, ameliorated renal histopathological damage, restored ferroptosis‑related markers, and suppressed local oxidative stress and inflammatory cytokine expression. Collectively, treatment with Emo/VE‑mcNVs improves AKI therapeutic outcomes through a synergistic antioxidant, anti‑inflammatory, and anti‑ferroptosis mechanism, offering a promising nanotherapeutic strategy for clinical management of acute kidney injury.