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pH-Sensitive Poly(β-amino ester)s Nanocarriers Facilitate the Inhibition of Drug Resistance in Breast Cancer Cells

1,2,†, 3,†, 1, 1, 1, 4,*, 1,2,* and 1,2,*
1
CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, Multidisciplinary Research Division, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing 100049, China
2
University of Chinese Academy of Sciences, Beijing 100049, China
3
John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138, USA
4
CNR Nanotec-Istituto di Nanotecnologia, Polo di Nanotecnologia, 73100 Lecce, Italy
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Nanomaterials 2018, 8(11), 952; https://doi.org/10.3390/nano8110952
Received: 16 October 2018 / Revised: 13 November 2018 / Accepted: 14 November 2018 / Published: 19 November 2018
(This article belongs to the Special Issue Biomedical Applications of Nanotechnology)
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PDF [9871 KB, uploaded 19 November 2018]
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Abstract

Multidrug resistance (MDR) remains an unmet challenge in chemotherapy. Stimuli-responsive nanocarriers emerge as a promising tool to overcome MDR. Herein, pH-sensitive poly(β-amino ester)s polymers (PHP)-based micellar nanoparticles were synthesized for enhanced doxorubicin (DOX) delivery in drug resistant breast cancer MCF-7/ADR cells. DOX-loaded PHP micelles showed rapid cell-internalization and lysosomal escape in MCF-7/ADR cells. The cytotoxicity assays showed relatively higher cell inhibition of DOX-loaded PHP micelles than that of free DOX against MCF-7/ADR cells. Further mechanistic studies showed that PHP micelles were able to inhibit P-glycoprotein (P-gp) activity by lowering mitochondrial membrane potentials and ATP levels. These results suggested that the enhanced antitumor effect might be attributed to PHP-mediated lysosomal escape and drug efflux inhibition. Therefore, PHP would be a promising pH-responsive nanocarrier for enhanced intracellular drug delivery and overcoming MDR in cancer cells. View Full-Text
Keywords: nanoparticles; pH responsive; poly(β-amino ester)s; doxorubicin; multidrug resistance nanoparticles; pH responsive; poly(β-amino ester)s; doxorubicin; multidrug resistance
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Zhou, M.; Zhang, X.; Xie, J.; Qi, R.; Lu, H.; Leporatti, S.; Chen, J.; Hu, Y. pH-Sensitive Poly(β-amino ester)s Nanocarriers Facilitate the Inhibition of Drug Resistance in Breast Cancer Cells. Nanomaterials 2018, 8, 952.

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