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Nano Research 2019, 12(4): 855-861 https://doi.org/10.1007/s12274-019-2308-9
Research Article | Issue | Published: 01 February 2019

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

Show Author's Information Chengxiang Zhang1,†,  Xinfu Zhang1, ,§,  Weiyu Zhao1,†,,, ,§,  Chunxi Zeng1,  Wenqing Li1,  Bin Li1,  Xiao Luo1,  Junan Li2,  Justin Jiang1,  Binbin Deng3,  David W. McComb3,4,  Yizhou Dong1,5,6,7,8,9( )
Division of Pharmaceutics & Pharmaceutical Chemistry,College of Pharmacy, The Ohio State University,Columbus,OH 43210,USA;
College of Pharmacy,The Ohio State University,Columbus,OH 43210,USA;
Center for Electron Microscopy and Analysis,The Ohio State University,Columbus,OH 43212,USA;
Department of Materials Science and Engineering,The Ohio State University,Columbus,OH 43210,USA;
Department of Biomedical Engineering,The Ohio State University,Columbus,OH 43210,USA;
The Center for Clinical and Translational Science,The Ohio State University,Columbus,OH 43210,USA;
The Comprehensive Cancer Center,The Ohio State University,Columbus,OH 43210,USA;
Dorothy M. Davis Heart & Lung Research Institute,The Ohio State University,Columbus,OH 43210,USA;
Department of Radiation Oncology,The Ohio State University,Columbus,OH 43210,USA;

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

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

Keywords:
combination therapy, paclitaxel amino lipid derived nanoparticles, mRNA therapeutics, triple-negative breast cancer
Topics:
Chemotherapy DiagnosisDiseasesGenesNanoparticlesProteinsSignal encodingTumors
Cite this article:
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 Research, 2019, 12(4): 855-861. https://doi.org/10.1007/s12274-019-2308-9
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Abstract Full text Electronic supplementary material About this article

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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Abstract
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Electronic supplementary material
About this article

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

Show Author's information Chengxiang Zhang1,†, Xinfu Zhang1, ,§, Weiyu Zhao1,†,,, ,§, Chunxi Zeng1, Wenqing Li1, Bin Li1, Xiao Luo1, Junan Li2, Justin Jiang1, Binbin Deng3, David W. McComb3,4, Yizhou Dong1,5,6,7,8,9( )
Division of Pharmaceutics & Pharmaceutical Chemistry,College of Pharmacy, The Ohio State University,Columbus,OH 43210,USA;
College of Pharmacy,The Ohio State University,Columbus,OH 43210,USA;
Center for Electron Microscopy and Analysis,The Ohio State University,Columbus,OH 43212,USA;
Department of Materials Science and Engineering,The Ohio State University,Columbus,OH 43210,USA;
Department of Biomedical Engineering,The Ohio State University,Columbus,OH 43210,USA;
The Center for Clinical and Translational Science,The Ohio State University,Columbus,OH 43210,USA;
The Comprehensive Cancer Center,The Ohio State University,Columbus,OH 43210,USA;
Dorothy M. Davis Heart & Lung Research Institute,The Ohio State University,Columbus,OH 43210,USA;
Department of Radiation Oncology,The Ohio State University,Columbus,OH 43210,USA;

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

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

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

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Publication history
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Acknowledgements

Publication history

Received: 28 December 2018
Revised: 17 January 2019
Accepted: 20 January 2019
Published: 01 February 2019
Issue date: April 2019

Copyright

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

Acknowledgements

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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