期刊
INTERNATIONAL JOURNAL OF PHARMACEUTICS
卷 573, 期 -, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.ijpharm.2019.118637
关键词
Hyaluronic acid; pH-sensitive; Embelin; Plasmid; Co-delivery
资金
- Macao Science and Technology Development Fund [083/2017/A2]
- Research Fund of the University of Macau [MYRG2016-00130-ICMS-QRCM, MYRG2017-00182-ICMS]
- Key Laboratory of Polymeric Composite & Functional Materials of Ministry of Education [PCFM-2016-03]
Triple negative breast cancer (TNBC) still lacks an effective targeted treatment. In this study, hyaluronic acid (HA)-mediated tumor targeting and pH-sensitive amphiphilic polymeric nanoparticles were designed and prepared to co-deliver the anticancer drug embelin (EMB) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) plasmid (pTRAIL) (EMB/TRAIL-HA/PBAE-PEI) for synergistic anti-breast cancer efficacy. These pH-sensitive amphiphilic polymeric nanoparticles were formed using the amphiphilic polymers polyethyleneimine (PEI)-poly[(1,6-hexanediol)-diacrylate-beta-5-hydroxyamylamine] (PBAE), which was synthesized via Michael addition polymerization. Taking advantage of the specific binding between HA and CD44, which is highly expressed in MDA-MB-231 TNBC cells, the HA-coated nanoparticles increased drug uptake in MDA-MB231 TNBC cells compared with MCF-7 non-TNBC cells with lower CD44 expression. Moreover, EMB/TRAIL-HA/PBAE-PEI exhibited enhanced cytotoxic and pro-apoptotic effects against MDA-MB-231 cells compared with free EMB and EMB- or pTRAIL-loaded nanoparticles via activation of caspase 3/7, an increase in reactive oxygen species levels, and inhibition of the expressions of apoptosis-related proteins. These results demonstrated that EMB/TRAIL-HA/PBAE-PEI exerted enhanced cytotoxic and pro-apoptotic effects against MDA-MB-231 cells and showed great potential for TNBC treatment.
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