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

  • Chengxiang Zhang
  • Xinfu Zhang
  • Weiyu Zhao
  • Chunxi Zeng
  • Wenqing Li
  • Bin Li
  • Xiao Luo
  • Junan Li
  • Justin Jiang
  • Binbin Deng
  • David W. McComb
  • Yizhou DongEmail author
Research Article

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.

Keywords

paclitaxel amino lipid derived nanoparticles mRNA therapeutics combination therapy triple-negative breast cancer 

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Notes

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.

Supplementary material

12274_2019_2308_MOESM1_ESM.pdf (1.9 mb)
Chemotherapy drugs derived nanoparticles encapsulating mRNA encoding tumor suppressor proteins to treat triple-negative breast cancer

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Copyright information

© Tsinghua University Press and Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Chengxiang Zhang
    • 1
  • Xinfu Zhang
    • 1
  • Weiyu Zhao
    • 1
  • Chunxi Zeng
    • 1
  • Wenqing Li
    • 1
  • Bin Li
    • 1
  • Xiao Luo
    • 1
  • Junan Li
    • 2
  • Justin Jiang
    • 1
  • Binbin Deng
    • 3
  • David W. McComb
    • 3
    • 4
  • Yizhou Dong
    • 1
    • 5
    • 6
    • 7
    • 8
    • 9
    Email author
  1. 1.Division of Pharmaceutics & Pharmaceutical Chemistry, College of PharmacyThe Ohio State UniversityColumbusUSA
  2. 2.College of PharmacyThe Ohio State UniversityColumbusUSA
  3. 3.Center for Electron Microscopy and AnalysisThe Ohio State UniversityColumbusUSA
  4. 4.Department of Materials Science and EngineeringThe Ohio State UniversityColumbusUSA
  5. 5.Department of Biomedical EngineeringThe Ohio State UniversityColumbusUSA
  6. 6.The Center for Clinical and Translational ScienceThe Ohio State UniversityColumbusUSA
  7. 7.The Comprehensive Cancer CenterThe Ohio State UniversityColumbusUSA
  8. 8.Dorothy M. Davis Heart & Lung Research InstituteThe Ohio State UniversityColumbusUSA
  9. 9.Department of Radiation OncologyThe Ohio State UniversityColumbusUSA

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