pH-Sensitive Poly(β-amino ester)s Nanocarriers Facilitate the Inhibition of Drug Resistance in Breast Cancer Cells.
Mengxue ZhouXingcai ZhangJin XieRongxiang QiHuiru LuStefano LeporattiJun ChenYi HuPublished in: Nanomaterials (Basel, Switzerland) (2018)
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.
Keyphrases
- drug delivery
- cancer therapy
- breast cancer cells
- drug resistant
- multidrug resistant
- induced apoptosis
- drug release
- cell cycle arrest
- oxidative stress
- cell death
- endoplasmic reticulum stress
- single cell
- stem cells
- squamous cell carcinoma
- emergency department
- acinetobacter baumannii
- pi k akt
- bone marrow
- radiation therapy
- locally advanced
- hyaluronic acid