THE EFFECT OF SOLID LIPID NANOPARTICLES ON TAMOXIFEN-RESISTANT BREAST CANCER CELLS
To overcome the acquired Tamoxifen (Tam) resistance in Tam-resistant breast cancer cells without damaging normal cells, we have examined the therapeutic efficacy of Tam-loaded solid lipid nanoparticles (SLNs). Tam-loaded SLNs were produced by hot homogenization method. After characterization, in vitro cytotoxic and apoptotic activity of Tam-SLNs were evaluated in MCF7, MCF7-TamR (Tam-resistant breast cancer cells) and MCF10A cells. Tam-SLNs had an average size nearly 300 nm and a zeta potential of approximately-40 mV. In vitro cytotoxicity results showed that Tam-SLNs indicated the cytotoxic and apoptotic activity on MCF7 and MCF7-TamR cells. We found that MCF7-TamR cell viability was also suppressed significantly by Tam-SLNs and thus, Tam-SLNs could delay and overcome Tam-resistance (p<0.05). Furthermore, the Tam-SLNs did not induce apoptosis on MCF10A control cells. The lowest MCF10A cell viability was 83.0% whereas MCF7 and MCF7-TamR (Râ†” and Râ†‘) cells viability are reduced to 21.98%, 27.5% and 29.4% at 10 ÂµM of Tam-SLNs, respectively (p<0.05). The obtained results were supported by apoptosis assays. SLNs-delivery system provided therapeutic efficacy to overcome Tam-resistance thanks to unique features of SLNs including small size, drug accumulation in the tumor site and controlled drug release. Therefore, Tam-SLNs may have therapeutic potential for the treatment of TAM-resistant breast cancer.
2. Kassam F, Enright K, Dent R, Dranitsaris G, Myers J, Flynn C, et al. Survival outcomes for patients with metastatic triple-negative breast cancer: implications for clinical practice and trial design. Clin Breast Cancer 2009;9:29â€“33.
3. GarcÃa-Becerra R, Santos N, DÃaz L, Camacho J. Mechanisms of resistance to endocrine therapy in breast cancer: focus on signaling pathways, miRNAs and genetically based resistance. Int J Mol Sci 2012;14:108â€“45.
4. Nass N, Kalinski T. Tamoxifen resistance: from cell culture experiments towards novel biomarkers. Pathol Res Pract 2015;211:189â€“97.
5. Viedma-RodrÃ¯guez R, Baiza-Gutman L, Salamancaâ€‘Gomez F, Diazâ€‘Zaragoza M, MartÃ¯nez-Hernandez G, Ruiz Esparzaâ€‘Garrido R, et al. Mechanisms associated with resistance to tamoxifen in estrogen receptor-positive breast cancer (Review). Oncol Rep 2014;32:3â€“15.
6. Sutradhar KB, Amin ML. Nanotechnology in cancer drug delivery and selective targeting. ISRN Nanotechnol 2014. Doi.org/10.1155/2014/939378. [Article in Press]
7. Markman JL, Rekechenetskiy A, Holler E, Ljubimova JY. Nanomedicine therapeutic approaches to overcome cancer drug resistance. Adv Drug Delivery Rev 2013;65:1866â€“79.
8. LasoÅ„ E, Ogonowski J. Solid lipid nanoparticlesâ€“characteristics, application and obtaining. Chem Int 2011;65:960â€“7.
9. Muller RH, Keck CM. Challenges and solutions for the delivery of biotech drugs-A review of drug nanocrystal technology and lipid nanoparticles. J Biotechnol 2004;113:151â€“70.
10. Bhaskar K, Anbu J, Ravichandiran V, Venkateswarlu V, Rao YM. Lipid nanoparticles for transdermal delivery of flurbiprofen: formulation, in vitro, ex vivo and in vivo studies. Lipids Health Dis 2009;8:6.
11. GÃ¼ney G, Kutlu HM, GenÃ§ L. Preparation and characterization of ascorbic acid loaded solid lipid nanoparticles and investigation of their apoptotic effects. Colloids Surf B 2014;121:270â€“80.
12. Dikmen G, Guney G, Genc L. Characterization of solid lipid nanoparticles containing caffeic acid and determination of its effects on MCF-7 cells. Recent Pat Anticancer Drug Discovery 2015;10:224â€“32.
13. Clarke R, Tyson JJ, Dixon JM. Endocrine resistance in breast cancerâ€“an overview and update. Mol Cell Endocrinol 2015;418:220â€“34.
14. Groenendijk FH, Bernards R. Drug resistance to targeted therapies: DÃ©jÃ vu all over again. Mol Oncol 2014;8:1â€“17.
15. Hu CMJ, Zhang L. Nanoparticle-based combination therapy toward overcoming drug resistance in cancer. Biochem Pharmacol 2012;83:1104â€“11.
16. Ravikumara NR, Madhusudhan B. Chitosan nanoparticles for tamoxifen delivery and cytotoxicity to MCF-7 and Vero cells. Pure Appl Chem 2011;83:2027â€“40.
17. Sant T, Moreira A, AntÃ´nio M, Oliveira M De, Nele M, Pinto JC. Effect of tamoxifen in RAFT mini-emulsion polymerization during the synthesis of polymer nanoparticles. Technical Sci Session 2014;24:25â€“30.
18. Lin YL, Chen CH, Wu HY, Tsai NM, Jian TY, Chang YC, et al. Inhibition of breast cancer with transdermal tamoxifen-encapsulated lipoplex. J Nanobiotechnol Biomed Central 2016;14:11.
19. Abbasalipourkabir R, Salehzadeh A, Abdullah R. Cytotoxicity of tamoxifen-loaded solid lipid nanoparticles. Delivery Nanoparticle 2009;59â€“70.
20. Ostad SN, Dehnad S, Nazari ZE, Fini ST, Mokhtari N, Shakibaie M, et al. Cytotoxic activities of silver nanoparticles and silver ions in parent and tamoxifen-resistant T47d human breast cancer cells and their combination effects with tamoxifen against resistant cells. Avicenna J Med Biotechnol 2010; 2:187â€“96.
21. Devalapally H, Duan Z, Seiden MV, Amiji MM. Modulation of drug resistance in ovarian adenocarcinoma by enhancing intracellular ceramide using tamoxifen-loaded biodegradable polymeric nanoparticles. Clin Cancer Res 2008;14:3193â€“203.