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Chemotherapy drugs derived nanoparticles encapsulating mRNA encoding tumor suppressor proteins to treat triple-negative breast cancer

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Abstract

Triple-negative breast cancer (TNBC) is one type of the most aggressive breast cancers with poor prognosis. It is of great urgency to develop new therapeutics for treating TNBC. Based on current treatment guideline and genetic information of TNBC, a combinational therapy platform integrating chemotherapy drugs and mRNA encoding tumor suppressor proteins may become an efficacious strategy. In this study, we developed paclitaxel amino lipid (PAL) derived nanoparticles (NPs) to incorporate both chemotherapy drugs and P53 mRNA. The PAL P53 mRNA NPs showed superior properties compared to Abraxane® and Lipusu® used in the clinic including high paclitaxel loading capacity (24 wt.%, calculated by paclitaxel in PAL), PAL encapsulation efficiency (94.7% ± 6.8%) and mRNA encapsulation efficiency (88.7% ± 0.7%). Meanwhile, these NPs displayed synergetic cytotoxicity of paclitaxel and P53 mRNA in cultured TNBC cells. More importantly, we demonstrated in vivo anti-tumor efficacy of PAL P53 mRNA NPs in an orthotopic TNBC mouse model. Overall, these chemotherapy drugs derived mRNA NPs provide a new platform to integrate chemotherapy and personalized medicine using tumor genetic information, and therefore represent a promising approach for TNBC treatment.

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Acknowledgements

This work was supported by the Maximizing Investigators’ Research Award R35GM119679 from the National Institute of General Medical Sciences as well as the start-up fund from the College of Pharmacy at The Ohio State University. C. X. Z. acknowledges the support from the Professor Sylvan G. Frank Graduate Fellowship.

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Author notes

  1. Xinfu Zhang

    Present address: Present address: State Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian, 116024, China

  2. Chengxiang Zhang, Xinfu Zhang, and Weiyu Zhao contributed equally to this work.

Authors and Affiliations

  1. Division of Pharmaceutics & Pharmaceutical Chemistry, College of Pharmacy, The Ohio State University, Columbus, OH, 43210, USA

    Chengxiang Zhang, Xinfu Zhang, Weiyu Zhao, Chunxi Zeng, Wenqing Li, Bin Li, Xiao Luo, Justin Jiang & Yizhou Dong

  2. College of Pharmacy, The Ohio State University, Columbus, OH, 43210, USA

    Junan Li

  3. Center for Electron Microscopy and Analysis, The Ohio State University, Columbus, OH, 43212, USA

    Binbin Deng & David W. McComb

  4. Department of Materials Science and Engineering, The Ohio State University, Columbus, OH, 43210, USA

    David W. McComb

  5. Department of Biomedical Engineering, The Ohio State University, Columbus, OH, 43210, USA

    Yizhou Dong

  6. The Center for Clinical and Translational Science, The Ohio State University, Columbus, OH, 43210, USA

    Yizhou Dong

  7. The Comprehensive Cancer Center, The Ohio State University, Columbus, OH, 43210, USA

    Yizhou Dong

  8. Dorothy M. Davis Heart & Lung Research Institute, The Ohio State University, Columbus, OH, 43210, USA

    Yizhou Dong

  9. Department of Radiation Oncology, The Ohio State University, Columbus, OH, 43210, USA

    Yizhou Dong

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  1. Chengxiang Zhang
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Correspondence to Yizhou Dong.

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12274_2019_2308_MOESM1_ESM.pdf

Chemotherapy drugs derived nanoparticles encapsulating mRNA encoding tumor suppressor proteins to treat triple-negative breast cancer

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Zhang, C., Zhang, X., Zhao, W. et al. Chemotherapy drugs derived nanoparticles encapsulating mRNA encoding tumor suppressor proteins to treat triple-negative breast cancer. Nano Res. 12, 855–861 (2019). https://doi.org/10.1007/s12274-019-2308-9

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