Related Experiment Video
Updated: Mar 9, 2026
Monitoring of Nanodrug Accumulation in Murine Breast Cancer Metastases
Published on: August 23, 2024
MicroRNA-200c delivered by solid lipid nanoparticles enhances the effect of paclitaxel on breast cancer stem cell
Jingwen Liu1, Tingting Meng1, Ming Yuan1
1Department of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou.
Background:
One of the major obstacles in the treatment of breast cancer is breast cancer stem cells (BCSC) which are resistant to standard chemotherapeutic drugs. It has been proven that microRNA-200c (miR-200c) can restore sensitivity to microtubule-targeting chemotherapeutic drugs by reducing the expression of class III β-tubulin. In this study, combination therapy with miR-200c and paclitaxel (PTX) mediated by lipid nanoparticles was investigated as an alternative strategy against BCSC.
Materials And Methods:
A cationic lipid 1,2-dioleoyl-3-trimethylammonium-propane was strategically selected to formulate solid lipid nanoparticles (SLN) for miR-200c delivery. Nanostructured lipid carriers (NLC) with 20 wt% oleic acid were prepared for PTX delivery. Mammospheres, which gained the characteristics of BCSC, were used as a cell model to evaluate the efficiency of combination therapy.
Results:
The cationic SLN could condense anionic miRNA to form SLN/miRNA complexes via charge interactions and could protect miRNA from degradation by ribonuclease. SLN/miR-200c complexes achieved 11.6-fold expression of miR-200c after incubation for 24 hours, compared with that of Lipofectamine™ 2000/miR-200c complexes (*P<0.05). Intracellular drug release assay proved that miRNA can be released from SLN/miRNA complexes efficiently in 12 hours after cellular uptake. After BCSC were transfected with SLN/miR-200c, the expression of class III β-tubulin was effectively downregulated and the cellular cytotoxicity of PTX-loaded NLC (NLC/PTX) against BCSC was enhanced significantly (**P<0.01).
Conclusion:
The results indicated that the cationic SLN could serve as a promising carrier for miRNA delivery. In addition, the combination therapy of miR-200c and PTX revealed a novel therapeutic strategy for the treatment of BCSC.
Insights
Combination therapy using microRNA-200c (miR-200c) and paclitaxel (PTX) delivered via lipid nanoparticles shows promise for overcoming breast cancer stem cell (BCSC) drug resistance.
Area of Science:
- Nanotechnology in drug delivery
- Molecular oncology
- Biomedical engineering
Background:
- Breast cancer stem cells (BCSCs) are a significant challenge due to their resistance to conventional chemotherapy.
- MicroRNA-200c (miR-200c) can re-sensitize BCSCs to chemotherapy by downregulating class III β-tubulin.
- Targeting BCSCs is crucial for improving breast cancer treatment outcomes.
Purpose of the Study:
- To investigate the combination therapy of miR-200c and paclitaxel (PTX) for targeting breast cancer stem cells (BCSCs).
- To evaluate the efficacy of lipid nanoparticles in delivering miR-200c and PTX for synergistic anti-BCSC effects.
- To develop a novel therapeutic strategy for overcoming BCSC chemoresistance.
Main Methods:
- Formulation of solid lipid nanoparticles (SLN) for miR-200c delivery using a cationic lipid.
- Preparation of nanostructured lipid carriers (NLC) for paclitaxel (PTX) delivery.
- Utilized mammospheres as a cell model to mimic BCSC characteristics and assess combination therapy efficacy.
Main Results:
- Cationic SLN effectively condensed and protected miR-200c, achieving significantly higher expression compared to commercial transfection agents.
- SLN/miR-200c complexes demonstrated efficient intracellular release of miR-200c within 12 hours.
- Combination therapy with SLN/miR-200c and NLC/PTX significantly downregulated class III β-tubulin and enhanced cytotoxicity against BCSCs.
Conclusions:
- Cationic solid lipid nanoparticles (SLN) are effective carriers for microRNA (miRNA) delivery.
- The combined administration of miR-200c and paclitaxel (PTX) represents a promising therapeutic approach for treating breast cancer stem cells (BCSCs).
- This study highlights a novel strategy to overcome chemoresistance in breast cancer.
