期刊
BIOMATERIALS
卷 103, 期 -, 页码 183-196出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2016.06.053
关键词
DNA origami; Nanomedicine; Cancer targeting; Apoptosis
资金
- Natural Science Foundation of China [21271002]
- National High-level personnel of special support program
- National High Technology Research and Development Program of China [SS2014AA020538]
- Science Foundation for Distinguished Young Scholars of Guangdong Province [S2013050014667]
- Foundation for High-level Talents in Higher Education of Guangdong
- YangFan Innovative AMP
- Entepreneurial Research Team Project [201312H05]
- Guangdong Special Support Program
- Guangdong Frontier and Key Technological Innovation Special Funds [2014B050505012]
The use of metal complexes in cancer treatment is hampered by the insufficient accumulation in tumor regions and observable systemic toxicity due to their nonspecificity in vivo. Herein we present a cancer targeted DNA origami as biocompatible nanocarrier of metal complexes to achieve advanced antitumor effect. The formation of unique tetrahedral nanostructure of DNA cages effectively enhances the interaction between ruthenium polypyridyl complexes (RuPOP) and the cages, thus increasing the drug loading efficacy. Conjugation of biotin to the DNA-based nanosystem (Bio-cage@Ru) enhances its specific cellular uptake, drug retention and cytotoxicity against HepG2 cells. Different from free RuPOP and the cage itself, Bio-cage@Ru translocates to cell nucleus after internalization, where it undergoes self-immolative cleavage in response to DNases, leading to triggered drug release and induction of ROS-mediated cell apoptosis. Moreover, in the nude mice model, the nanosystem specifically accumulates in tumor sites, thus exhibits satisfactory in vivo antitumor efficacy, and alleviates the damage of liver, kidney, lung and heart function of nude mice induced by RuPOP and tumor xenografts. Collectively, this study demonstrates a strategy for construction of biocompatible and cancer-targeted DNA origami with enhanced anticancer efficacy and reduced toxicity for next-generation cancer therapy. (C) 2016 Elsevier Ltd. All rights reserved.
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