pH-Sensitive Poly(β-amino ester)s Nanocarriers Facilitate the Inhibition of Drug Resistance in Breast Cancer Cells
Mengxue Zhou,
Xingcai Zhang,
Jin Xie,
Rongxiang Qi,
Huiru Lu,
Stefano Leporatti,
Jun Chen,
Yi Hu
Affiliations
Mengxue Zhou
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
Xingcai Zhang
John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138, USA
Jin Xie
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
Rongxiang Qi
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
Huiru Lu
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
Stefano Leporatti
CNR Nanotec-Istituto di Nanotecnologia, Polo di Nanotecnologia, 73100 Lecce, Italy
Jun Chen
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
Yi Hu
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
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.
