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MicroRNA-200c delivered by solid lipid nanoparticles enhances the effect of paclitaxel on breast cancer stem cell

Authors Liu J, Meng T, Yuan M, Wen LJ, Cheng BL, Liu N, Huang X, Hong Y, Yuan H, Hu FQ

Received 28 April 2016

Accepted for publication 11 July 2016

Published 12 December 2016 Volume 2016:11 Pages 6713—6725

DOI https://doi.org/10.2147/IJN.S111647

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 3

Editor who approved publication: Dr Lei Yang


Jingwen Liu,1 Tingting Meng,1 Ming Yuan,1 Lijuan Wen,1 Bolin Cheng,1 Na Liu,1 Xuan Huang,2 Yun Hong,3 Hong Yuan,1 Fuqiang Hu1

1Department of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 2Department of Pharmacy, School of Medicine Science, Jiaxing University, Jiaxing, 3The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China

Background: One of the major obstacles in the treatment of breast cancer is breast cancer stem cells (BCSC) which are resistant to standard chemotherapeutic drugs. It has been proven that microRNA-200c (miR-200c) can restore sensitivity to microtubule-targeting chemothera­peutic drugs by reducing the expression of class III β-tubulin. In this study, combination therapy with miR-200c and paclitaxel (PTX) mediated by lipid nanoparticles was investigated as an alternative strategy against BCSC.
Materials and methods: A cationic lipid 1,2-dioleoyl-3-trimethylammonium-propane was strategically selected to formulate solid lipid nanoparticles (SLN) for miR-200c delivery. Nanostructured lipid carriers (NLC) with 20 wt% oleic acid were prepared for PTX delivery. Mammospheres, which gained the characteristics of BCSC, were used as a cell model to evaluate the efficiency of combination therapy.
Results: The cationic SLN could condense anionic miRNA to form SLN/miRNA complexes via charge interactions and could protect miRNA from degradation by ribonuclease. SLN/miR-200c complexes achieved 11.6-fold expression of miR-200c after incubation for 24 hours, compared with that of Lipofectamine™ 2000/miR-200c complexes (*P<0.05). Intracellular drug release assay proved that miRNA can be released from SLN/miRNA complexes efficiently in 12 hours after cellular uptake. After BCSC were transfected with SLN/miR-200c, the expression of class III β-tubulin was effectively downregulated and the cellular cytotoxicity of PTX-loaded NLC (NLC/PTX) against BCSC was enhanced significantly (**P<0.01).
Conclusion: The results indicated that the cationic SLN could serve as a promising carrier for miRNA delivery. In addition, the combination therapy of miR-200c and PTX revealed a novel therapeutic strategy for the treatment of BCSC.

Keywords: breast cancer stem cells, microRNA-200c, paclitaxel, solid lipid nanoparticles, nanostructured lipid carriers, combination therapy

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