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Chemotherapy drugs derived nanoparticles encapsulating mRNA encoding tumor suppressor proteins to treat triple-negative breast cancer |
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| Authors: | Zhang Chengxiang Zhang Xinfu Zhao Weiyu Zeng Chunxi Li Wenqing Li Bin Luo Xiao Li Junan Jiang Justin Deng Binbin McComb David W. Dong Yizhou |
| Affiliation: | 1.Division of Pharmaceutics & Pharmaceutical Chemistry, College of Pharmacy, The Ohio State University, Columbus, OH, 43210, USA ;2.College of Pharmacy, The Ohio State University, Columbus, OH, 43210, USA ;3.Center for Electron Microscopy and Analysis, The Ohio State University, Columbus, OH, 43212, USA ;4.Department of Materials Science and Engineering, The Ohio State University, Columbus, OH, 43210, USA ;5.Department of Biomedical Engineering, The Ohio State University, Columbus, OH, 43210, USA ;6.The Center for Clinical and Translational Science, The Ohio State University, Columbus, OH, 43210, USA ;7.The Comprehensive Cancer Center, The Ohio State University, Columbus, OH, 43210, USA ;8.Dorothy M. Davis Heart & Lung Research Institute, The Ohio State University, Columbus, OH, 43210, USA ;9.Department of Radiation Oncology, The Ohio State University, Columbus, OH, 43210, USA ; |
| 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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