Small Warriors of Nature: Novel Red Emissive Chlorophyllin Carbon Dots Harnessing Fenton‐Fueled Ferroptosis for In Vitro and In Vivo Cancer Treatment

Abstract The appeal of carbon dots (CDs) has grown recently, due to their established biocompatibility, adjustable photoluminescence properties, and excellent water solubility. For the first time in the literature, copper chlorophyllin‐based carbon dots (Chl‐D CDs) are successfully synthesized. Chl‐D CDs exhibit unique spectroscopic traits and are found to induce a Fenton‐like reaction, augmenting photodynamic therapy (PDT) efficacies via ferroptotic and apoptotic pathways. To bolster the therapeutic impact of Chl‐D CDs, a widely used cancer drug, temozolomide, is linked to their surface, yielding a synergistic effect with PDT and chemotherapy. Chl‐D CDs' biocompatibility in immune cells and in vivo models showed great clinical potential.Proteomic analysis was conducted to understand Chl‐D CDs' underlying cancer treatment mechanism. The study underscores the role of reactive oxygen species formation and pointed toward various oxidative stress modulators like aldolase A (ALDOA), aldolase C (ALDOC), aldehyde dehydrogenase 1B1 (ALDH1B1), transaldolase 1 (TALDO1), and transketolase (TKT), offering a deeper understanding of the Chl‐D CDs' anticancer activity. Notably, the Chl‐D CDs' capacity to trigger a Fenton‐like reaction leads to enhanced PDT efficiencies through ferroptotic and apoptotic pathways. Hence, it is firmly believed that the inherent attributes of Chl‐CDs can lead to a secure and efficient combined cancer therapy.