Self-assembled multifunctional DNA nanoflowers for the circumvention of multidrug resistance in targeted anticancer drug delivery

作     者：Lei Mei Guizhi Zhu Liping Qiu Cuichen Wu Huapei Chen Hao Liang Sena Cansiz Yifan Lv Xiaobing Zhang Weihong Tan 

作者机构：Molecular Sciences and Biomedicine Laboratory State Key Laboratory for Chemo/Biosensing and Chemometrics College of Chemistry and Chemical Engineering College of Biology Collaborative Innovation Center for Chemistry and Molecular Medicine Hunan University Changsha 410082 China Departments of Chemistry Physiology and Functional Genomics Center for Research at the Bio/Nano Interface Shands Cancer Center UF Genetics Institute and McKnight Brain Institute University of Florida Gainesville FL 32611-7200 USA Laboratory of Molecular Imaging and Nanomedicine National Institute of Biomedical Imaging and Bioengineering National Institutes of Health Bethesda MD 20892 USA 

出 版 物：《Nano Research》 (纳米研究（英文版）)

年 卷 期：2015年第8卷第11期

页      面：3447-3460页

核心收录：

学科分类：0710[理学-生物学] 071010[理学-生物化学与分子生物学] 081704[工学-应用化学] 07[理学] 08[工学] 0817[工学-化学工程与技术] 

基　　金：Acknowledgements We thank Dr. M. M. Gottesman at the National Cancer Institute for providing MCF7/MDR cells. We thank Dr. K. R. Williams for manuscript review. This work was supported by the National Institutes of Health (Nos. GM079359 and CA133086) and National Key Scientific Program of China (No. 2011CB911000)  the National Natural Science Foundation of China (NSFC) (Nos. 21325520  J1210040  20975034 and 21177036)  the Foundation for Innovative Research Groups of NSFC (No. 21221003)  the National Key Natural Science Foundation of China (No. 21135001)  National Instru- mentation Program (No. 2011YQ030124)  the Ministry of Education of China (No. 20100161110011)  and the Hunan Provincial Natural Science Foundation (Nos. 12JJ6012 and 11JJ1002) 

主　　题：aptamer rolling circle replication self-assembly DNA nanotechnology multidrug resistance targeted cancer therapy 

摘      要：Cancer chemotherapy has been limited by its side effects and multidrug resistance （MDR）, the latter of which is partially caused by drug efflux from cancer cells. Thus, targeted drug delivery systems that can circumvent MDR are needed. Here, we report multifunctional DNA nanoflowers （NFs） for targeted drug delivery to both chemosensitive and MDR cancer cells that circumvented MDR in both leukemia and breast cancer cell models. NFs are self-assembled via potential co-precipitation of DNA and magnesium pyrophosphate generated by rolling circle replication, during which NFs are incorporated using aptamers for specific cancer cell recognition, fluorophores for bioimaging, and doxorubicin （Dox）- binding DNA for drug delivery. NF sizes are tunable （down to N200 nm in diameter）, and the densely packed drug-binding motifs and porous intrastructures endow NFs with a high drug-loading capacity （71.4%, wt/wt）. Although the Dox- loaded NFs （NF-Dox） are stable at physiological pH, drug release is facilitated under acidic or basic conditions. NFs deliver Dox into target chemosensitive and MDR cancer cells, preventing drug efflux and enhancing drug retention in MDR cells. NF-Dox induces potent cytotoxicity in both target chemosensitive cells and MDR cells, but not in nontarget cells, thus concurrently circumventing MDR and reducing side effects. Overall, these NFs are promising tools for circumventing MDR in targeted cancer therapy.