Cabeza, LauraEl-Hammadi, Mazen M.Ortiz, RaulCayero-Otero, Maria D.Jimenez-Lopez, JuliaPerazzoli, GloriaMartin-Banderas, LuciaBaeyens, Jose M.Melguizo, ConsolacionPrados, Jose2023-05-032023-05-032022-02-20Cabeza L, El-Hammadi MM, Ortiz R, Cayero-Otero MD, Jiménez-López J, Perazzoli G, et l. Evaluation of poly (lactic-co-glycolic acid) nanoparticles to improve the therapeutic efficacy of paclitaxel in breast cancer. Bioimpacts. 2022;12(6):515-531.2228-5652http://hdl.handle.net/10668/21817Introduction: 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 alpha-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, MISs 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 MRCSs from MCF-7 and E0771, respectively). PTX-PLGA nanoformulation preserved PTX's mechanism of action and increased its cell internalization. Interestingly, PTX-PLG A NI's not only reduced the tumor volume of treated mice hut 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.enAttribution-NonCommercial 4.0 Internationalhttp://creativecommons.org/licenses/by-nc/4.0/PaclitaxelPLGABreast cancerCancer stem cellsMice xenograftsPlga-based nanoparticlesAlbumin-bound paclitaxelTumor-targeted deliveryDrug-deliveryIn-vitroIntracellular pharmacokineticsBlood-pressureOvarian-cancerChallengesWomenFemalePaclitaxelBreast NeoplasmsTubulinTissue Distributionnile redMCF-7 CellsSolubilityTumor BurdenInhibitory Concentration 50SpleenMice, Inbred C57BLAntineoplastic AgentsCell CycleLungDrug ResistanceLiverDrug ResistanceNeoplastic Stem Cellsresearch articleopen accessAntineoplásicosBazoCarga tumoralCiclo celularConcentración 50 inhibidoraCélulas MCF-7Células madre neoplásicasDistribución tisularHígadoFemeninoNeoplasias de la mamaPaclitaxelPulmónTubulina (Proteína)10.34172/bi.2022.234332228-5660https://bi.tbzmed.ac.ir/Inpress/bi-23433.pdf768180300001