Hyaluronic Acid-Modified Nanoparticles Self-Assembled from Linoleic Acid-Conjugated Chitosan for the Codelivery of miR34a and Doxorubicin in Resistant Breast Cancer

被引:13
作者
Yang, Xiaoxia [1 ]
Shang, Pengfei [1 ]
Ji, Jianbo [1 ]
Malichewe, Christina [1 ]
Yao, Zhiyin [2 ]
Liao, Jing [1 ]
Du, Dandan [1 ]
Sun, Chao [1 ]
Wang, Lei [1 ]
Tang, Ya-jie [3 ]
Guo, Xiuli [1 ,3 ]
机构
[1] Shandong Univ, Cheeloo Coll Med, Sch Pharmaceut Sci, Dept Pharmacol,Key Lab Chem Biol,Minist Educ, Jinan 250012, Peoples R China
[2] Shandong Univ, Key Lab Colloid & Interface Chem, Minist Educ, Jinan 250100, Peoples R China
[3] Shandong Univ, State Key Lab Microbial Technol, Qingdao 266237, Peoples R China
基金
美国国家科学基金会;
关键词
chitosan; miR34a; Dox; codelivery system; resistance; therapy; CELL-PROLIFERATION; SIGNALING PATHWAY; DRUG-RESISTANCE; CO-DELIVERY; MIGRATION; INVASION; PROGRESSION; MICELLES; SUPPRESS; SNAIL;
D O I
10.1021/acs.molpharmaceut.1c00459
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
In this study, a chitosan-based, self-assembled nanosystem that codelivered microRNA34a (miR34a) and doxorubicin (Dox) with hyaluronic acid (HA) modification (named CCmDH NPs) was developed to reverse the resistance of breast cancer (BCa) cells to Dox. The CCmDH NPs had a diameter of 180 +/- 8.3 nm and a zeta potential of 16.5 mV with a slow-release effect for 96 h. The codelivery system could protect miR34a from nuclease and serum degradation and transport miR34a and Dox into drug-resistant MCF-7/A cells. In addition, the CCmDH NPs could inhibit proliferation and promote apoptosis by regulating the protein expression of B-cell lymphoma-2 (Bcl-2) and poly(ADP-ribose) polymerase (PARP) and inhibit invasion, metastasis, and adhesion by regulating E-cadherin, N-cadherin, MMP2, CD44, and Snail molecules. The CCmDH NPs induced a 73.7% tumor reduction in xenograft tumor growth in nude mice in vivo. This study provides evidence for the anticancer activity of CCmDH NPs carrying Dox and miR34a in BCa, especially metastatic Dox-resistant BCa models.
引用
收藏
页码:2 / 17
页数:16
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