Evaluation of poly (lactic-co-glycolic acid) nanoparticles to improve the therapeutic efficacy of paclitaxel in breast cancer

聚乳酸-乙醇酸纳米粒子改善紫杉醇对乳腺癌治疗效果的评价

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作者:Laura Cabeza, Mazen M El-Hammadi, Raul Ortiz, Maria D Cayero-Otero, Julia Jiménez-López, Gloria Perazzoli, Lucia Martin-Banderas, Jose M Baeyens, Consolación Melguizo, Jose Prados

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.

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.

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