A multifunctional DNA origami as carrier of metal complexes to achieve enhanced tumoral delivery and nullified systemic toxicity

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• 作者：Yanyu Huang ; Wei Huang ; Leung Chan ; Binwei Zhou ; Tianfeng Chen ; ^{tchentf@jnu.edu.cn" class="auth_mail" title="E-mail the corresponding author}
• 关键词：DNA origami ; Nanomedicine ; Cancer targeting ; Apoptosis
• 刊名：Biomaterials
• 出版年：2016
• 出版时间：October 2016
• 年：2016
• 卷：103
• 期：Complete
• 页码：183-196
• 全文大小：4105 K

文摘

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.