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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2015-09-15

AUTHORS

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

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. More... »

PAGES

3447-3460

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s12274-015-0841-8

DOI

http://dx.doi.org/10.1007/s12274-015-0841-8

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1003298486

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/27774139


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71 nanoflowers
72 nontarget cells
73 pH
74 physiological pH
75 potent cytotoxicity
76 pyrophosphate
77 recognition
78 release
79 replication
80 resistance
81 retention
82 side effects
83 size
84 specific cancer cell recognition
85 system
86 target
87 therapy
88 tool
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