Bioinspired zinc-doped carbon dots protect against polystyrene microplastic-induced spermatogenic dysfunction through Nrf2 activation and cuproptosis suppression.

Polystyrene microplastics (PS-MPs) are increasingly recognized for their detrimental effects on reproductive health, particularly in the male reproductive system. While mitochondrial oxidative stress is recognized as a driver of MPs-induced reproductive injury, it remains unclear whether this process involves cuproptosis, a newly identified copper-dependent form of regulated cell death, and elucidating this potential link is critical for alleviating such damage. Here, we report that PS-MPs exposure induces testicular injury and spermatogenic dysfunction in mice, associated with redox imbalance, copper transport defects, and upregulation of the cuproptosis regulators Ferredoxin 1 (FDX1) and Lipoic Acid Synthetase (LIAS). In turn, zinc-doped trifolirhizin-derived carbon dots (ZnTFZCDs) were rationally designed via a one-step hydrothermal strategy, embedding the antioxidant properties of a natural flavonoid and the reproductive-protective role of zinc into a biocompatible carbon nanoplatform. ZnTFZCDs are well-dispersed carbon dots rich in oxygen/nitrogen-containing groups with Zn coordination, and demonstrate favorable biosafety without overt cytotoxicity, hemolysis, or organ damage.