Journal
BIOMATERIALS
Volume 35, Issue 14, Pages 4333-4344Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2014.02.006
Keywords
Nanoparticles; Co-delivery; MicroRNA-34a; Doxorubicin; Combined therapy
Funding
- MOST 973 program [2010CB934004]
- NSFC [81272453]
- National High Technology Research and Development Program of China (863 Program) [2007AA021107]
- Program for New Century Excellent Talents in University [39015001200801]
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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.
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