Laura Cabeza
1,2,3 
, Mazen M. El-Hammadi
4 , Raul Ortiz
1,2,3 , Maria D. Cayero-Otero
4, Julia Jiménez-López
1,3 , Gloria Perazzoli
1,3 , Lucia Martin-Banderas
4 , Jose M. Baeyens
5 , Consolación Melguizo
1,2,3* , Jose Prados
1,2,3 1 Institute of Biopathology and Regenerative Medicine (IBIMER), Center of Biomedical Research (CIBM), University of Granada, 18100 Granada, Spain
2 Department of Anatomy and Embryology, Faculty of Medicine, University of Granada, 18071 Granada, Spain
3 Biosanitary Institute of Granada (ibs.GRANADA), SAS-University of Granada, 18014 Granada, Spain
4 Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of Seville, 41012 Sevilla, Spain
5 Department of Pharmacology, Institute of Neuroscience, Biomedical Research Center (CIBM), University of Granada, 18100, Granada, Spain
Abstract
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.