Synthesis of Zinc Oxide-Doped Carbon Dots for Treatment of Triple-Negative Breast Cancer

Mengqi Wang,1,* Shuting Lan,2,* Mingjun Song,3 Rongrong Zhang,2 Wenqi Zhang,2 Xiaomei Sun,2 Gang Liu2 1College of Life Science and Oceanography, Weifang University, Weifang, Shandong, People’s Republic of China; 2Key Laboratory of Medical Cell Biology, Affiliated Hospital of Inner Mongolia Medical University, Hohhot, Inner Mongolia, People’s Republic of China; 3College of Chemical Engineering and Environmental Chemistry, Weifang University, Weifang, Shandong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Mengqi Wang; Gang Liu, Email [email protected]; [email protected]: The anti-cancer properties of zinc oxide-doped carbon dots (CDs/ZnO) in inhibiting triple-negative breast cancer (TNBC) progression merit more investigation.Methods: With citric acid as the carbon source, urea applied as the nitrogen source, and zinc oxide (ZnO) used as a reactive dopant, CDs/ZnO were synthesized by microwave heating in the current study, followed by the characterization and biocompatibility assessments. Subsequently, the anti-cancer capabilities of CDs/ZnO against TNBC progression were evaluated by various biochemical and molecular techniques, including viability, proliferation, migration, invasion, adhesion, clonogenicity, cell cycle distribution, apoptosis, redox homeostasis, metabolome, and transcriptome assays of MDA-MB-231 cells. Additionally, the in vivo anti-cancer potentials of CDs/ZnO against TNBC progression were analyzed using TNBC xenograft mouse models.Results: The biocompatibility of CDs/ZnO was supported by the non-significant changes in the pathological and physiological parameters in the CDs/ZnO treated mice, alongside a non-cytotoxic effect of CDs/ZnO on the proliferation of normal cells. Notably, the CDs/ZnO treatments effectively decreased the viability, proliferation, migration, invasion, adhesion, and clonogenicity of MDA-MB-231 cells. Furthermore, the CDs/ZnO treatments induced cell cycle arrest, apoptosis, redox imbalance, metabolome disturbances, and transcriptomic alterations of MDA-MB-231 cells by regulating the MAPK signaling pathway. Additionally, the CDs/ZnO treatments markedly suppressed the in vivo tumor growth in the TNBC xenograft mouse models.Conclusion: In this study, we synthesized CDs/ZnO via microwave heating, using citric acid as the carbon source, urea as the nitrogen source, and ZnO as a reactive dopant. We confirmed the biosafety and potent anti-cancer efficacy of CDs/ZnO in inhibiting TNBC progression by disrupting malignant cell behaviors through modulation of the MAPK signaling pathway.Keywords: zinc, carbon dots, triple-negative breast cancer, MAPK signaling pathway