Evaluation of poly (lactic-co-glycolic acid) nanoparticles to improve the therapeutic efficacy of paclitaxel in breast cancer Cabeza Montilla, Laura Ortiz Quesada, Raúl Jiménez López, Julia Perazzoli, Gloria Baeyens Cabrera, José Manuel Melguizo Alonso, Consolación Prados Salazar, José Carlos Paclitaxel PLGA Breast cancer Cancer stem cells Mice xenografits Financial support from the V Plan Propio (University of Seville). This work was also supported by Consejeria de Salud de la Junta de Andalucia (PI-0102-2017 and P18-HO-3882) and Instituto de Salud Carlos III (ISCIII) (Project PI19/01478) (FEDER). Introduction: Paclitaxel (PTX) is a cornerstone in the treatment of breast cancer, the most common type of cancer in women. However, this drug has serious limitations, including lack of tissue-specificity, poor water solubility, and the development of drug resistance. The transport of PTX in a polymeric nanoformulation could overcome these limitations. Methods: In this study, PLGA-PTX nanoparticles (NPs) were assayed in breast cancer cell lines, breast cancer stem cells (CSCs) and multicellular tumor spheroids (MTSs) analyzing cell cycle, cell uptake (Nile Red-NR-) and α-tubulin expression. In addition, PLGA-PTX NPs were tested in vivo using C57BL/6 mice, including a biodistribution assay. Results: PTX-PLGA NPs induced a significant decrease in the PTX IC50 of cancer cell lines (1.31 and 3.03-fold reduction in MDA-MB-231 and E0771 cells, respectively) and CSCs. In addition, MTSs treated with PTX-PLGA exhibited a more disorganized surface and significantly higher cell death rates compared to free PTX (27.9% and 16.3% less in MTSs from MCF-7 and E0771, respectively). PTX-PLGA nanoformulation preserved PTX’s mechanism of action and increased its cell internalization. Interestingly, PTX-PLGA NPs not only reduced the tumor volume of treated mice but also increased the antineoplastic drug accumulation in their lungs, liver, and spleen. In addition, mice treated with PTX-loaded NPs showed blood parameters similar to the control mice, in contrast with free PTX. Conclusion: These results suggest that our PTX-PLGA NPs could be a suitable strategy for breast cancer therapy, improving antitumor drug efficiency and reducing systemic toxicity without altering its mechanism of action. 2022-04-04T11:42:21Z 2022-04-04T11:42:21Z 2022-01-15 info:eu-repo/semantics/article Cabeza, L... [et al.] (2022). Evaluation of poly (lactic-co-glycolic acid) nanoparticles to improve the therapeutic efficacy of paclitaxel in breast cancer. BioImpacts, 2022, 12(x), x-x. doi: [10.34172/bi.2022.23433] http://hdl.handle.net/10481/74094 10.34172/bi.2022.23433 eng http://creativecommons.org/licenses/by-nc/3.0/es/ info:eu-repo/semantics/openAccess Atribución-NoComercial 3.0 España Tabriz University of Medical Sciences and Health Services