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Published on: July 20, 2019
Anti-Breast Cancer Effects of Carbon Quantum Dots: In Vivo Angiogenesis and Arginase Co-Inhibition
Gurmeet Singh1, Somedutta Maity2, Desh Deepak Yadav1
1School of Biomedical Engineering, Indian Institute of Technology (BHU), Varanasi, UP 221005, India.
Abstract:
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.
Insights
Carbon quantum dots (CQDs) from Azadirachta indica inhibit arginase, reducing breast cancer (BC) tumor growth and promoting immune response. This novel approach offers a promising treatment for aggressive BC, even in patients unresponsive to conventional therapies.
Area of Science:
- Oncology
- Immunology
- Materials Science
Background:
- Breast cancer (BC) utilizes immune-regulating enzymes like arginase to evade immune surveillance.
- Arginase inhibition is therapeutically challenging due to its essential role in the urea cycle and potential for severe side effects like hyperammonemia.
Purpose of the Study:
- To investigate the efficacy of Azadirachta indica-derived carbon quantum dots (CQDs) as a novel therapeutic strategy for BC treatment by targeting arginase.
- To evaluate the anti-tumorigenic, anti-angiogenic, and immune-modulating effects of these CQDs in vitro and in vivo.
Main Methods:
- Treatment of BC-bearing mice with Azadirachta indica-derived CQDs.
- Assessment of tumor remission, cell growth inhibition, and immune response markers (e.g., IFN-γ, IL-6, IgG).
- Histological analysis to evaluate cancer cell and immune cell infiltration post-treatment.
Main Results:
- CQDs achieved 68 ± 5% tumor remission and 58 ± 5% cell growth inhibition via arginase inhibition.
- Treatment led to upregulation of key immune markers (IFN-γ, IL-6, IL-8, IL-21, TLR4, LAT-1, T-cell marker, IgG) and downregulation of TNFα and IL-1β.
- Histology confirmed increased cancer cell inhibition and immune cell infiltration.
Conclusions:
- Azadirachta indica-derived CQDs demonstrate significant anti-cancer properties by inhibiting arginase, offering a new therapeutic avenue for aggressive BC.
- These CQDs enhance anti-tumor immunity and show potential for treating other cancers and patients resistant to current therapies.
