Chemotherapy drugs derived nanoparticles encapsulating mRNA encoding tumor suppressor proteins to treat triple-negative breast cancer
Open accessAbstract
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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Restoration of the tumour suppressor gene TP53 can induce tumour cell apoptosis and sensitize tumour cells to chemotherapeutics in vivo.
“For example, restoration of the tumour suppressor gene TP53 can induce tumour cell apoptosis and sensitize tumour cells to chemotherapeutics in vivo118,218.”
From Lipid nanoparticles for mRNA delivery (2021) · cites this paper as [118]
Paclitaxel-derived lipids allow integration of chemotherapies and gene therapies for the treatment of cancer.
“Such multifunctional lipid materials include self-adjuvant lipids, which boost vaccine efficacy117,119, and paclitaxel-derived lipids, which allow integration of chemotherapies and gene therapies for the treatment of cancer118.”
From Lipid nanoparticles for mRNA delivery (2021) · cites this paper as [118]
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References 45 · Cited by 61
- Authors
- Zhang, C., Zhang, X., Zhao, W., Zeng, C., Li, W., Li, B., Luo, X., Li, J., Jiang, J., Deng, B., McComb, D. W., & Dong, Y.
- Affiliations
- The Ohio State University (US)
- Corresponding author
- Dong, Yizhou
- ORCID
- Venue
- Nano Research
- Publisher
- Tsinghua University Press
- Published
- 2019-02-01
- Volume
- 12
- Issue
- 4
- Pages
- 855-861
- ISSN
- 1998-0000 (ISSN-L)
- 1998-0124
- PMC
- PMC6858063
- OpenAlex
- W2912083307
- Cited by
- 61
- References
- 45
- Citations by year
- 2026: 3 · 2025: 12 · 2024: 7 · 2023: 12 · 2022: 10 · 2021: 8 · 2020: 6 · 2019: 3
- FWCI
- 1.91
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nano Research (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Ohio State University
- National Institute of General Medical Sciences (R35GM119679)
- Topics
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Physical Sciences › Materials Science › Polymers and Plastics › Dendrimers and Hyperbranched Polymers
- Keywords
- triple-negative breast cancer, nanoparticles, mRNA encapsulation, p53 mRNA, tumor suppressor proteins, chemotherapy delivery, combination therapy, orthotopic tumor model, personalized medicine
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