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Updated: Sep 24, 2025
Monitoring of Nanodrug Accumulation in Murine Breast Cancer Metastases
Published on: August 23, 2024
Development of double strand RNA mPEI nanoparticles and application in treating invasive breast cancer
Rui Liu1, Li-Min Mu1, Jing Bai1
1State Key Laboratory of Natural and Biomimetic Drugs, Beijing Key Laboratory of Molecular Pharmaceutics and New Drug System, School of Pharmaceutical Sciences, Peking University Beijing 100191 China luwl@bjmu.edu.cn +86 10 82802683 +86 10 82802683.
Abstract:
Triple negative breast cancer (TNBC) has been characterized as a very heterogeneous subtype, and is more invasive and non-expressing of the genes for the estrogen receptor (ER), progesterone receptor (PR) and HER2/neu, with poor prognosis, and hence the efficacy of regular chemotherapy is very limited. Here, we report a kind of double strand RNA (dsRNA) mPEI nanoparticle for treatment of invasive TNBC. The studies were performed on TNBC cells in vitro and in TNBC cancer-bearing mice. The results showed that dsRNA mPEI nanoparticles were able to effectively transfect cells, and demonstrated a strong capability in knocking-down the Fra-1 gene and down-stream MMP-1 and MMP-9 genes in TNBC cells and TNBC cancer-bearing mice, thereby inhibiting the invasion and migration of cells. After intratumoral injection, dsRNA mPEI nanoparticles exhibited a robust anticancer efficacy in TNBC cancer-bearing mice, and the anticancer efficacy was superior to that of paclitaxel. In conclusion, dsRNA mPEI nanoparticles are able to effectively treat aggressive TNBC, and the mechanism studies reveal that they take effect by knocking-down Fra-1 relevant genes, hence interfering in transcription and translation of the genes, which are necessary for growth and metastasis of TNBC. Therefore, the present study offers a new and promising formulation and strategy for effective treatment of TNBC.
Insights
New dsRNA mPEI nanoparticles effectively treat triple-negative breast cancer (TNBC) by inhibiting gene expression essential for tumor growth and metastasis. This novel nanoparticle formulation shows superior efficacy compared to paclitaxel in preclinical models.
Area of Science:
- Oncology
- Nanomedicine
- Gene Therapy
Background:
- Triple-negative breast cancer (TNBC) is an aggressive subtype with limited treatment options due to its heterogeneity and lack of specific biomarkers.
- Current chemotherapy efficacy for TNBC is often restricted, necessitating the development of novel therapeutic strategies.
Purpose of the Study:
- To investigate the potential of double-strand RNA (dsRNA) complexed with mPEI nanoparticles as a therapeutic agent for invasive TNBC.
- To evaluate the efficacy and mechanism of action of dsRNA mPEI nanoparticles in vitro and in vivo models of TNBC.
Main Methods:
- dsRNA mPEI nanoparticles were synthesized and characterized.
- In vitro studies assessed cellular transfection and gene knockdown of Fra-1, MMP-1, and MMP-9 in TNBC cells.
- In vivo studies involved TNBC cancer-bearing mice treated with intratumoral injection of dsRNA mPEI nanoparticles, with efficacy compared to paclitaxel.
Main Results:
- dsRNA mPEI nanoparticles demonstrated effective cellular transfection and significant knockdown of Fra-1, MMP-1, and MMP-9 genes.
- The nanoparticles inhibited TNBC cell invasion and migration.
- Intratumoral administration of dsRNA mPEI nanoparticles showed robust anticancer efficacy in vivo, outperforming paclitaxel.
Conclusions:
- dsRNA mPEI nanoparticles represent a promising new formulation for the effective treatment of aggressive TNBC.
- The therapeutic effect is mediated by the knockdown of Fra-1 and related genes, disrupting TNBC growth and metastasis.
- This approach offers a novel strategy for managing TNBC, addressing limitations of conventional therapies.
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