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Assessing the Potential of Chitosan/Polylactide Nanoparticles for Delivery of Therapeutics for Triple-Negative Breast Cancer Treatment

  • S’Dravious DeVeaux
  • Cheryl T. GomillionEmail author
Article
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Abstract

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.

Lay Summary

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.

Keywords

Chitosan PLA Nanoparticles Drug delivery Tamoxifen Triple-negative breast cancer 

Notes

Funding Information

Funding for this work was provided by the University of Georgia Faculty Research Grant.

References

  1. 1.
    Schneider AP, Zainer CM, Kubat CK, Mullen NK, Windisch AK. The breast cancer epidemic: 10 facts. Linacre Q. 2014;81(3):244–77.CrossRefGoogle Scholar
  2. 2.
    DeSantis CE, Ma J, Goding Sauer A, Newman LA, Jemal A. Breast cancer statistics, 2017, racial disparity in mortality by state. CA Cancer J Clin. 2017;67(6):439–48.CrossRefGoogle Scholar
  3. 3.
    American Cancer Society. Breast cancer facts & figures 2017-2018. Atlanta: American Cancer Society, Inc.; 2017.Google Scholar
  4. 4.
    Foulkes WD, Smith IE, Reis-Filho JS. Triple-negative breast Cancer. N Engl J Med. 2010;363(20):1938–48.CrossRefGoogle Scholar
  5. 5.
    McPherson K, Steel CM, Dixon JM. Breast cancer—epidemiology, risk factors, and genetics. BMJ: Br Med J. 2000;321(7261):624–8.CrossRefGoogle Scholar
  6. 6.
    Severson TM, Peeters J, Majewski I, Michaut M, Bosma A, Schouten PC, et al. BRCA1-like signature in triple negative breast cancer: molecular and clinical characterization reveals subgroups with therapeutic potential. Mol Oncol. 2015;9(8):1528–38.CrossRefGoogle Scholar
  7. 7.
    Newman LA, Kaljee LM. Health disparities and triple-negative breast cancer in African American women: a review. JAMA Surg. 2017;152(5):485–93.CrossRefGoogle Scholar
  8. 8.
    Haffty BG, Silber A, Matloff E, Chung J, Lannin D. Racial differences in the incidence of BRCA1 and BRCA2 mutations in a cohort of early onset breast cancer patients: African American compared to white women. J Med Genet. 2006;43(2):133–7.CrossRefGoogle Scholar
  9. 9.
    Boyle P. Triple-negative breast cancer: epidemiological considerations and recommendations. Ann Oncol. 2012;23(suppl_6):vi7–vi12.Google Scholar
  10. 10.
    Dietze EC, Sistrunk C, Miranda-Carboni G, O'Regan R, Seewaldt VL. Triple-negative breast cancer in African-American women: disparities versus biology. Nat Rev Cancer. 2015;15(4):248–54.CrossRefGoogle Scholar
  11. 11.
    Fisher ER, Land SR, Fisher B, Mamounas E, Gilarski L, Wolmark N. Pathologic findings from the National Surgical Adjuvant Breast and bowel project. Cancer. 2004;100(2):238–44.CrossRefGoogle Scholar
  12. 12.
    Thiruppathi R, et al. Nanoparticle functionalization and its potentials for molecular imaging. advanced. Science. 2016;4(3):1600279.Google Scholar
  13. 13.
    Aravind A, Jeyamohan P, Nair R, Veeranarayanan S, Nagaoka Y, Yoshida Y, et al. AS1411 aptamer tagged PLGA-lecithin-PEG nanoparticles for tumor cell targeting and drug delivery. Biotechnol Bioeng. 2012;109(11):2920–31.CrossRefGoogle Scholar
  14. 14.
    Mu Q, Kievit FM, Kant RJ, Lin G, Jeon M, Zhang M. Anti-HER2/neu peptide-conjugated iron oxide nanoparticles for targeted delivery of paclitaxel to breast cancer cells. Nanoscale. 2015;7(43):18010–4.CrossRefGoogle Scholar
  15. 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
  16. 16.
    Kumari A, Yadav SK, Yadav SC. Biodegradable polymeric nanoparticles based drug delivery systems. Colloids Surf B: Biointerfaces. 2010;75(1):1–18.CrossRefGoogle Scholar
  17. 17.
    Gavasane AJ. Synthetic biodegradable polymers used in controlled drug delivery system: an overview. Clin Pharmacol Biopharm. 2014;3(2).Google Scholar
  18. 18.
    Dev A, Binulal NS, Anitha A, Nair SV, Furuike T, Tamura H, et al. Preparation of poly (lactic acid)/chitosan nanoparticles for anti-HIV drug delivery applications. Carbohydr Polym. 2010;80(3):833–8.CrossRefGoogle Scholar
  19. 19.
    Landriscina A, Rosen J, Friedman AJ. Biodegradable chitosan nanoparticles in drug delivery for infectious disease. Nanomedicine. 2015;10(10):1609–19.CrossRefGoogle Scholar
  20. 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
  21. 21.
    van der Lubben IM, Kersten G, Fretz MM, Beuvery C, Coos Verhoef J, Junginger HE. Chitosan microparticles for mucosal vaccination against diphtheria: oral and nasal efficacy studies in mice. Vaccine. 2003;21(13):1400–8.CrossRefGoogle Scholar
  22. 22.
    Manna S, Holz MK. Tamoxifen action in ER-negative breast Cancer. Sign Transduct Insights. 2016;5:1–7.Google Scholar
  23. 23.
    Wang Q, Cheng Y, Wang Y, Fan Y, Li C, Zhang Y, et al. Tamoxifen reverses epithelial–mesenchymal transition by demethylating miR-200c in triple-negative breast cancer cells. BMC Cancer. 2017;17(1):492.CrossRefGoogle Scholar
  24. 24.
    He C, Hu Y, Yin L, Tang C, Yin C. Effects of particle size and surface charge on cellular uptake and biodistribution of polymeric nanoparticles. Biomaterials. 2010;31(13):3657–66.CrossRefGoogle Scholar
  25. 25.
    Anderson M, Moshnikova A, Engelman DM, Reshetnyak YK, Andreev OA. Probe for the measurement of cell surface pH in vivo and ex vivo. Proc Natl Acad Sci U S A. 2016;113(29):8177–81.CrossRefGoogle Scholar
  26. 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
  27. 27.
    Kajstura M, Halicka HD, Pryjma J, Darzynkiewicz Z. Discontinuous fragmentation of nuclear DNA during apoptosis revealed by discrete “sub-G1” peaks on DNA content histograms. Cytometry A. 2007;71A(3):125–31.CrossRefGoogle Scholar
  28. 28.
    Yuan XJ. Voltage-gated K+ currents regulate resting membrane potential and [Ca2+]i in pulmonary arterial myocytes. Circ Res. 1995;77(2):370–8.CrossRefGoogle Scholar
  29. 29.
    Warren EAK, Payne CK. Cellular binding of nanoparticles disrupts the membrane potential. RSC Adv. 2015;5(18):13660–6.CrossRefGoogle Scholar

Copyright information

© The Regenerative Engineering Society 2019

Authors and Affiliations

  1. 1.School of Chemical, Materials, and Biomedical EngineeringUniversity of GeorgiaAthensUSA

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