Anthocyanin-functionalized selenocysteine nanotherapeutics alleviate cisplatin nephrotoxicity by inhibiting oxidative stress and ferroptosis.

Although cisplatin (CDDP) remains a widely used chemotherapeutic agent in clinical cancer treatment, severe oxidative stress and inflammatory responses induced by CDDP are still major causes of acute kidney injury (AKI) in patients. Our previous studies have demonstrated that anthocyanins and selenocysteine (SeC) exhibit potent antioxidant and anti-inflammatory properties. Here, we successfully synthesized a synergistic nanotherapeutic, cyanidin-3-O-glucoside-functionalized SeC nanoparticles (C3G@SeC NPs), which significantly alleviated CDDP-induced damage in HK-2 cells by inhibiting oxidative stress and ferroptosis. In vivo, C3G@SeC NPs alleviated AKI by regulating the MAPK and ferroptosis pathways. Furthermore, C3G@SeC NPs regulated the populations of M2 macrophages, Treg cells, CD4(+) T cells, MDSCs, and NK cells disrupted by CDDP in the kidney and spleen tissues of AKI mice, ultimately inhibiting the inflammatory response. In summary, this study synthesizes a synergistic nanotherapeutic and systematically elucidates its anti-AKI mechanisms, indicating C3G@SeC NPs may be an ideal nanoparticle for alleviating CDDP nephrotoxicity.