Hyaluronic acid-chitosan nanoparticles for co-delivery of M1R-34a and doxorubicin in therapy against triple negative breast cancer

被引：434

作者：

Deng, Xiongwei ^{[1
,2
]}

Cao, Minjun ^{[2
]}

Zhang, Jiakun ^{[1
,3
]}

Hu, Kelei ^{[1
,2
]}

Yin, Zhaoxia ^{[2
]}

Zhou, Zhixiang ^{[2
]}

Xiao, Xiangqian ^{[2
]}

Yang, Yishu ^{[2
]}

Sheng, Wang ^{[2
]}

Wu, Yan ^{[1
]}

Zeng, Yi ^{[2
]}

机构：

[1] Chinese Acad Sci, Key Lab Biomed Effects Nanomat & Nanosafety, Natl Ctr Nanosci & Technol China, Beijing 100190, Peoples R China

[2] Beijing Univ Technol, Coll Life Sci & Bioengn, Beijing 100124, Peoples R China

[3] CAAS, Inst Plant Protect, Key Lab Pesticide Chem & Applicat, MOA, Beijing 100194, Peoples R China

来源：

BIOMATERIALS | 2014年 / 35卷 / 14期

基金：

国家高技术研究发展计划(863计划);

关键词：

Nanoparticles; Co-delivery; MicroRNA-34a; Doxorubicin; Combined therapy; MICRORNA; NANOCARRIER; SIRNA; APOPTOSIS; PROMISE; TUMORS;

D O I：

10.1016/j.biomaterials.2014.02.006

中图分类号：

R318 [生物医学工程];

学科分类号：

0831 ;

摘要：

Metastatic relapse, development of drug resistance in cancer cells and adverse side effects of chemotherapeutic agents are the major obstacles for effective chemotherapy against triple-negative breast cancer. To address these problems, miR-34a, a potent endogenous tumor suppressive molecule in breast cancer, was co-encapsulated with doxorubicin (DOX) into hyaluronic acid (HA)-chitosan (CS) nanoparticles (NPs) and simultaneously delivered into breast cancer cells for improved therapeutic effects of drug. DOX-miR-34a co-loaded HA-CS NPs were successfully prepared through ionotropic gelation method in water. In vitro and in vivo experiments showed that miR-34a and DOX can be efficiently encapsulated into HA-CS NPs and delivered into tumor cells or tumor tissues and enhance anti-tumor effects of DOX by suppressing the expression of non-pump resistance and anti-apoptosis proto-oncogene BcI-2. In addition, intracellular restoration of miR-34a inhibited breast cancer cell migration via targeting Notch-I signaling. The obtained data suggest that co-delivery of DOX and miR-34a could achieve synergistic effects on tumor suppression and nanosystem-based co-delivery of tumor suppressive miRNAs and chemotherapeutic agents may be a promising combined therapeutic strategy for enhanced anti-tumor therapy. (C) 2014 Elsevier Ltd. All rights reserved.

引用

页码：4333 / 4344

页数：12

共 45 条

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