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Research Article

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

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.

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Graphical Abstract

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 nanoparticlesmRNA therapeuticscombination therapytriple-negative breast cancer

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Nano Research
Volume 12 Issue 4,
April 2019
Pages 855-861
DOI: 10.1007/s12274-019-2308-9
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
Topics:
Chemotherapy DiagnosisDiseasesGenesNanoparticlesProteinsSignal encodingTumors

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Received: 28 December 2018
Revised: 17 January 2019
Accepted: 20 January 2019
Published: 01 February 2019
© Tsinghua University Press and Springer-Verlag GmbH Germany, part of Springer Nature 2019
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