Assessing the Potential of Chitosan/Polylactide Nanoparticles for Delivery of Therapeutics for Triple-Negative Breast Cancer Treatment
- 5 Downloads
Patients diagnosed with triple-negative breast cancer (TNBC) typically have a poor prognosis with limited therapeutic options. Due to the lack of common hormone receptors (estrogen, progesterone, and HER2 receptors) on TNBC cells, therapeutics that target these hormone receptors are ineffective for TNBC. Thus, alternative modalities for treating TNBC are sought. Namely, nanoparticle-based drug delivery methods have been explored for cancer therapy, as nanoparticles are able to target tumor cells through means other than surface hormone receptors. Here, we fabricated chitosan (CS)/polylactide (PLA) nanoparticles to deliver tamoxifen, an anticancer compound, to treat TNBC. The nanoparticles were prepared via a solvent evaporation method and characterized using dynamic light scattering and FTIR. The encapsulation efficiency and in vitro drug release were measured at relevant physiological conditions. In addition, the viability of breast cancer cells was observed using Alamar Blue® cell viability assay, PicoGreen® DNA assay, and FITC Annexin V apoptosis assay after treatment. The average nanoparticle size for the tamoxifen-loaded nanoparticles was 146 ± 6.5 nm. TNBC cell death and cell cycle arrest was observed with increased drug-loaded nanoparticle concentration. The results of this work indicate that CS/PLA nanoparticles can be used as potential drug delivery vehicles to deliver anticancer drugs, resulting in increased efficacy for treating triple-negative breast cancer.
Triple-negative breast cancer (TNBC) is a type of breast cancer that is resistant to and cannot be killed with commonly used cancer drugs. This is problematic as the cancer will continue to grow uncontrollably, leading to more patient deaths each year. African-Americans are diagnosed more often with aggressive forms of TNBC that spread throughout the body; however, TNBC affects people of all ethnicities. To counter this problem, we prepared small particles containing a cancer drug and evaluated the success of these particles to effectively kill TNBC cells. The drug is gradually released into the TNBC environment affecting how they behave, which in turn kills the cancer cells.
KeywordsChitosan PLA Nanoparticles Drug delivery Tamoxifen Triple-negative breast cancer
Funding for this work was provided by the University of Georgia Faculty Research Grant.
- 3.American Cancer Society. Breast cancer facts & figures 2017-2018. Atlanta: American Cancer Society, Inc.; 2017.Google Scholar
- 9.Boyle P. Triple-negative breast cancer: epidemiological considerations and recommendations. Ann Oncol. 2012;23(suppl_6):vi7–vi12.Google Scholar
- 12.Thiruppathi R, et al. Nanoparticle functionalization and its potentials for molecular imaging. advanced. Science. 2016;4(3):1600279.Google Scholar
- 15.Schrand AM, Rahman MF, Hussain SM, Schlager JJ, Smith DA, Syed AF. Metal-based nanoparticles and their toxicity assessment. Wiley interdisciplinary reviews: nanomedicine and. Nanobiotechnology. 2010;2(5):544–68.Google Scholar
- 17.Gavasane AJ. Synthetic biodegradable polymers used in controlled drug delivery system: an overview. Clin Pharmacol Biopharm. 2014;3(2).Google Scholar
- 20.Kamel M, Hanafi M, Bassiouni M. Inhibition of elastase enzyme release from human polymorphonuclear leukocytes by N-acetyl-galactosamine and N-acetyl-glucosamine. Clin Exp Rheumatol. 1991;9(1):17–2.Google Scholar
- 22.Manna S, Holz MK. Tamoxifen action in ER-negative breast Cancer. Sign Transduct Insights. 2016;5:1–7.Google Scholar
- 26.Sutherland RL, Hall RE, Taylor IW. Cell proliferation kinetics of MCF-7 human mammary carcinoma cells in culture and effects of tamoxifen on exponentially growing and plateau-phase cells. Cancer Res. 1983;43(9):3998–4006.Google Scholar