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Nanomaterials (Basel). 2018 Nov 19;8(11). pii: E952. doi: 10.3390/nano8110952.

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

Author information

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. zhoumx@ihep.ac.cn.
2
University of Chinese Academy of Sciences, Beijing 100049, China. zhoumx@ihep.ac.cn.
3
John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138, USA. xingcai@mit.edu.
4
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. xiejin5739@163.com.
5
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. qrx198913@163.com.
6
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. luhuiru@ihep.ac.cn.
7
CNR Nanotec-Istituto di Nanotecnologia, Polo di Nanotecnologia, 73100 Lecce, Italy. stefano.leporatti@nanotec.cnr.it.
8
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. chenjun@ihep.ac.cn.
9
University of Chinese Academy of Sciences, Beijing 100049, China. chenjun@ihep.ac.cn.
10
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. huyi@ihep.ac.cn.
11
University of Chinese Academy of Sciences, Beijing 100049, China. huyi@ihep.ac.cn.

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.

KEYWORDS:

doxorubicin; multidrug resistance; nanoparticles; pH responsive; poly(β-amino ester)s

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