Intelligent nanoparticles based on Fenton reaction for chemo/chemodynamic therapy against cervical cancer

• cRCF effectively kills cervical cancer cells. • cRCF induces apoptosis and ferroptosis in cervical cancer cells. • cRCF represents a promising new approach for the treatment of cervical cancer. Cervical cancer is a malignant tumor that poses a significant threat to women’s health. Traditional chemotherapy (CT) is hindered by issues such as poor water solubility and inadequate targeting. Consequently, this study synthesized three amphiphilic molecules (PEG-SS-CPT, Fc-PEG-Fc, and cRGD-PEG-TK-DSPE) which were self-assembled to create intelligent nanoparticles, referred to as cRCF, for the purposes of synergistic CT and chemodynamic therapy (CDT). The cRCF nanoparticles can actively target tumor cells. Ferrocenecarboxylic acid (Fc) generates hydroxyl radicals via the Fenton reaction, thereby triggering ferroptosis. Elevated levels of glutathione (GSH) can cleave the disulfide bond, releasing the chemotherapeutic agent camptothecin (CPT), which induces apoptosis; additionally, the depletion of GSH further enhances the CDT effect. Both in vitro and in vivo experiments demonstrate that cRCF exhibits a significant anti-tumor effect, achieving an inhibition rate of 85.0 ± 6.9%, while also displaying favorable biocompatibility. This research provides a novel strategy for the treatment of cervical cancer that emphasizes high efficiency and low toxicity.