2023 AIChE Annual Meeting
Platinum Nanoparticles' Mechanism of Action in Triple Negative Breast Cancer
Nanotechnology has emerged as a potential therapeutic for cancer treatment. Metallic nanoparticles, such as gold and silver, have gained significant importance in nanomedicine. More importantly, platinum nanoparticles (PtNPs) have shown promising anticancer activity while maintaining low toxicity towards healthy cells. Triple negative breast cancer (TNBC) is an aggressive form of breast cancer that metastasizes rapidly and is currently only treated with toxic chemotherapeutics. Cisplatin, in particular, is a platinum-based therapy that works by entering the cell, binding to the DNA, and breaking the DNA, effectively disabling the cell's ability to proliferate. Cell viability tests using PtNPs treatments for TNBC, double-positive breast cancer (DPBC), cisplatin-resistant uterine sarcoma, and cardiac fibroblasts indicate that PtNPs works similarly to cisplatin, but only kills TNBC, leaving healthy cells unaffected. Additionally, the acidic environment of cancer cells can lead to more platinum ions, increasing PtNPs efficacy at killing TNBC. The mechanism of action of PtNPs needs to be more fully understood and to do so, ion release studies and cellular uptake studies were conducted. Acidic environments promote more ionization and the data shows that PtNPs in MES, a buffer at pH 5, has variably equal and higher release of platinum ions. Uptake of PtNPs by cancer cell lines and healthy fibroblasts was studied. Cancer cells are prone to devour more nutrients and resources than healthy cells, attributing to their increased proliferation rates. As such, it was expected that the cancer cell lines would have higher PtNPs uptake, especially TNBC. Surprisingly, the healthy fibroblasts were observed to have higher uptake levels than the cancer cell lines, with TNBC having the lowest uptake of PtNPs, implying that TNBC uptake PtNps through a different mechanism. Ongoing mice studies are being conducted as well to determine the efficacy of PtNPs in vivo. Preliminary data does show non-toxicity to the mice, further supporting PtNPs low toxicity towards healthy cells. References: Shim et. al 2017; Lopez et. al 2022. Acknowledgements: This research was funded by the New Jersey Health Foundation and NJIT's Undergraduate Research Innovation Grant. This research was also advised by Dr. Aida Lopez-Ruiz and Dr. Kathleen McEnnis. PtNPs formation was conducted by Prova Joy Foundatoin, Darshan Danak, and Pranav Prabhu.