期刊
JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART B-APPLIED BIOMATERIALS
卷 105, 期 5, 页码 1114-1125出版社
WILEY
DOI: 10.1002/jbm.b.33636
关键词
low-density lipoprotein; siRNA; reduction-sensitive; pH-sensitive; micelles; multidrug resistance; co-delivery; tumor-targeting therapy
资金
- National Natural Science Foundation of China [81571788, 81273463]
- Jiangsu Science and Technology Support Plan [BE2011670]
- Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD)
The development of effective and stable carriers of small interfering RNA (siRNA) is important for treating cancer with multidrug resistance (MDR). We developed a new gene and drug co-delivery system and checked its characteristics. Low-density lipoprotein (LDL) was coupled with N-succinyl chitosan (NSC) Lipoic acid (LA) micelles and co-delivered MDR1 siRNA and paclitaxel (PTX-siRNA/LDLNSC-LA) to enhance antitumor effects by silencing the MDR gene of tumors (Li et al., Adv Mater 2014; 26: 8217-8224). In our study, we developed a new type of containing paclitaxel-loaded micelles and siRNA-loaded LDL nanoparticle. This binary polymer is pH and reduction dualsensitive core-crosslinked micelles. PTX-siRNA/LDL-NSC-LA had an average particle size of (171.6 +/- 6.42) nm, entrapment efficiency of (93.92 +/- 1.06) %, and drug-loading amount of (12.35% +/- 60.87) %. In vitro, MCF-7 cells, high expressed LDL receptor, were more sensitive to this delivery system than to taxol VR and cell activity was inhibited significantly. Fluorescence microscopy showed that PTX-siRNA/LDL-NSC-LA was uptaken very conveniently and played a key role in antitumor activity. PTX-siRNA/LDL-NSC-LA protected the siRNA from degradation by macrophage phagocytosis and evidently down-regulated the level of mdr1 mRNA as well as the expression of P-gp. We tested the target ability of PTXsiRNA/LDL-NSC-LA in vivo in tumor-bearing nude mice. Results showed that this system could directly deliver siRNA and PTX to cancer cells. Thus, new co-delivering siRNA and antitumor drugs should be explored for solving MDR in cancer. (C) 2016 Wiley Periodicals, Inc.
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