g-C

Abstract

Ferroptosis induced by iron overload has been recognized as a critical factor in germ cell damage and subsequent male infertility. However, current ferroptosis inhibitors are often constrained by systemic side effects and limited targeting. Herein, we developed graphitic carbon nitride (g-C3N4) nanosheets as a multisite iron chelation strategy to inhibit iron overload-induced ferroptosis and prevent male reproductive dysfunction. Characterized by excellent stability and intrinsic fluorescence, the g-C3N4 nanosheets enable specific iron ion (Fe3+ and Fe2+) sequestration, exhibiting iron-responsive fluorescence quenching with remarkable selectivity and sensitivity. Both in vitro and in vivo studies confirmed that iron overload induces significant germ cell damage, whereas g-C3N4 nanosheets treatment targeted ferroptosis via the Nrf2 pathway, thereby preserving male reproductive function. Moreover, g-C3N4 exhibited excellent biosafety, with minimal cytotoxicity in vitro and no adverse effects in vivo. These findings highlight the potential of g-C3N4 nanosheets as a promising therapeutic platform for the treatment of ferroptosis-related diseases.

Key Findings

• g-C3N4 nanosheets effectively chelate iron ions (Fe3+ and Fe2+) to inhibit iron overload-induced ferroptosis.
• Treatment with g-C3N4 nanosheets activates the Nrf2 pathway, protecting germ cells from ferroptosis and preserving male reproductive function.
• g-C3N4 nanosheets demonstrate excellent biosafety with minimal cytotoxicity in vitro and no adverse effects in vivo.

Clinical Significance

Citation

Wang Lingling, Yang Fuyu, Ye Zhixinet al.. g-C Molecular pharmaceutics. 2026-Apr-11.