Copper/calcium co-doped carbon dots for targeted cancer therapy with dual-mode imaging and synergistic induction of cuproptosis and calcium-mediated apoptosis

Squamous cell carcinoma remains a highly aggressive malignancy with persistently high global incidence and mortality rates, posing significant challenges for effective treatment. Traditional chemotherapies lack specificity, leading to damage in normal tissues and severe side effects, highlighting the urgent need for targeted therapeutic strategies. In this study, copper and calcium co-doped carbon dots (Cu/Ca-CDs) were synthesized using a vacuum-confined heating method. These Cu/Ca-CDs demonstrated excellent tumor-targeting ability through specific binding to folate receptors on murine squamous cell carcinoma cell line (SCC7), facilitated by their pterin ring structure. Mechanistic studies revealed that Cu/Ca-CDs induced SCC7 tumor cell death through copper-induced cuproptosis and calcium overload-mediated apoptosis, as confirmed by Western blot, immunofluorescence staining, and Rhod-2 calcium probe analyses. The dual-mode imaging capability of Cu/Ca-CDs, enabled by fluorescence and computed tomography properties, allowed for real-time tracking of their distribution and accumulation within tumors. This imaging-guided approach ensured precise delivery to tumor tissues while minimizing damage to normal tissues. In vivo experiments demonstrated significant tumor volume reduction and increased survival rates in tumor-bearing mice treated with Cu/Ca-CDs, without any observed toxicity to normal tissues or changes in body weight, underscoring the efficacy and biosafety of Cu/Ca-CDs. These findings highlight Cu/Ca-CDs as a promising strategy for precision oncology, offering effective tumor targeting, dual-mode imaging, and synergistic anti-tumor efficacy with reduced side effects.