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

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Abstract

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 ∼200 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 Doxloaded 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.

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Author notes

  1. Guizhi Zhu

    Present address: Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, MD, 20892, USA

Authors and Affiliations

  1. 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

    Lei Mei, Guizhi Zhu, Liping Qiu, Huapei Chen, Hao Liang, Yifan Lv, Xiaobing Zhang & Weihong Tan

  2. 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

    Guizhi Zhu, Liping Qiu, Cuichen Wu, Sena Cansiz & Weihong Tan

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  1. Lei Mei
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Correspondence to Xiaobing Zhang or Weihong Tan.

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Mei, L., Zhu, G., Qiu, L. et al. Self-assembled multifunctional DNA nanoflowers for the circumvention of multidrug resistance in targeted anticancer drug delivery. Nano Res. 8, 3447–3460 (2015). https://doi.org/10.1007/s12274-015-0841-8

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