Anti-Breast Cancer Effects of Carbon Quantum Dots: In Vivo Angiogenesis and Arginase Co-Inhibition.

Breast cancer evades the immune system through immune-regulating enzymes. One of them is arginase, primarily produced in tumor-resident cells, especially by tumor-associated macrophages and myeloid-derived suppressor cells. This helps malignant tumors thrive and escape immune surveillance. However, targeting arginase is challenging because of its crucial role in the urea cycle. Pharmacological inhibitors of arginases have been linked to severe side effects in nitrogen metabolism, particularly hyperammonemia. Herein, therefore, we report on the arginase-inhibition-based in vitro and in vivo treatment of BC-bearing mice with carbon quantum dots (CQDs) derived from Azadirachta indica. These CQDs inhibit the arginase enzyme, thereby exhibiting anti-angiogenic and anti-proliferative properties. These CQDs contribute to 68 ± 5% remission of malignant tumors and 58 ± 5% inhibition of cell growth through arginase inhibition. This is particularly difficult to achieve with contemporary anti-cancer drugs. Protein upregulation of IFN-γ, IL-6, IL-8, IL-21, TLR4, LAT-1, T-cell marker, and IgG and downregulation of TNFα and IL-1β corroborate an increase in the anti-tumor immune response. Furthermore, histological results show an increase in the inhibition of cancer cells and an increase in immune cells after CQD treatment. Overall, the CQDs reported herein are paramount for the treatment of aggressive BC, which can further be used for the treatment of other cancers. The results further demonstrate that these CQDs can potentially be delivered to terminally ill patients who are not responding to contemporary therapies.