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Nano Research

Article Title

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

Authors

Chengxiang Zhang, Division of Pharmaceutics & Pharmaceutical Chemistry, College of Pharmacy, The Ohio State University, Columbus, OH 43210, USA
Xinfu Zhang, Division of Pharmaceutics & Pharmaceutical Chemistry, College of Pharmacy, The Ohio State University, Columbus, OH 43210, USA
Weiyu Zhao, Division of Pharmaceutics & Pharmaceutical Chemistry, College of Pharmacy, The Ohio State University, Columbus, OH 43210, USA
Chunxi Zeng, Division of Pharmaceutics & Pharmaceutical Chemistry, College of Pharmacy, The Ohio State University, Columbus, OH 43210, USA
Wenqing Li, Division of Pharmaceutics & Pharmaceutical Chemistry, College of Pharmacy, The Ohio State University, Columbus, OH 43210, USA
Bin Li, Division of Pharmaceutics & Pharmaceutical Chemistry, College of Pharmacy, The Ohio State University, Columbus, OH 43210, USA
Xiao Luo, Division of Pharmaceutics & Pharmaceutical Chemistry, College of Pharmacy, The Ohio State University, Columbus, OH 43210, USA
Junan Li, College of Pharmacy, The Ohio State University, Columbus, OH 43210, USA
Justin Jiang, Division of Pharmaceutics & Pharmaceutical Chemistry, College of Pharmacy, The Ohio State University, Columbus, OH 43210, USA
Binbin Deng, Center for Electron Microscopy and Analysis, The Ohio State University, Columbus, OH 43212, USA
David W. McComb, 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
Yizhou Dong, Division of Pharmaceutics & Pharmaceutical Chemistry, College of Pharmacy, 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

Keywords

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

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.

Graphical Abstract

Publisher

Tsinghua University Press

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