Hydroxyl-modified fullerene C70(OH)8 induces pyroptosis for cancer therapy

Abstract

Fullerene (C₇₀), a promising new photosensitizer, faces challenges in its biological applications due to its extreme hydrophobicity. In order to enhance the solubility of fullerene (C₇₀) and facilitate its biological applications, we synthesized a novel hydroxyl-modified fullerene compound (C₇₀(OH)₈) with excellent photosensitizing properties. The introduction of hydroxyl groups allows it to self-assemble with DSPE-PEG(2000); therefore, we prepared it as a nanomedicine (C₇₀(OH)₈@NP). Under white light irradiation, C₇₀(OH)₈@NP stimulates the production of reactive oxygen species (ROS). Furthermore, results have demonstrated that a substantial amount of ROS can also be generated within cells, resulting in cell death. We found that C₇₀(OH)₈@NP can induce both apoptosis and pyroptosis in HeLa cells and identified its mechanism of cell death through the activation of caspase 3/gasdermin E pathways. Importantly, C₇₀(OH)₈@NP demonstrates significant anti-tumor activity in a nude mouse tumor-bearing model. These results highlight the potential of novel fullerene compounds as photodynamic therapy agents.