Related Experiment Video
Updated: Nov 16, 2025
Preparation and Characterization of Individual and Multi-drug Loaded Physically Entrapped Polymeric Micelles
Published on: August 28, 2015
A paclitaxel and microRNA-124 coloaded stepped cleavable nanosystem against triple negative breast cancer
Chuanrong Chen1, Ming Shen2,3, Hongze Liao4
1State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200032, China.
Background:
Triple negative breast cancer (TNBC) is one of the most biologically aggressive breast cancers and lacks effective treatment options, resulting in a poor prognosis. Therefore, studies aiming to explore new therapeutic strategies for advanced TNBC are urgently needed. According to recent studies, microRNA-124 (miR124) not only inhibits tumour growth but also increases the sensitivity of TNBC to paclitaxel (PTX), suggesting that a platform combining PTX and miR124 may be an advanced solution for TNBC.
Results:
Herein, we constructed a stepped cleavable calcium phosphate composite lipid nanosystem (CaP/LNS) to codeliver PTX and miR124 (PTX/miR124-NP). PTX/miR124-NP exhibited superior tumor microenvironment responsive ability, in which the surface PEG layer was shed in the mildly acidic environment of tumor tissues and exposed oligomeric hyaluronic acid (o-HA) facilitated the cellular uptake of CaP/LNS by targeting the CD44 receptor on the surface of tumor cells. Inside tumour cells, o-HA detached from CaP/LNS due to the reduction of disulfide bonds by glutathione (GSH) and inhibited tumour metastasis. Then, PTX and miR124 were sequentially released from CaP/LNS and exerted synergistic antitumour effects by reversing the Epithelial-Mesenchymal Transition (EMT) process in MDA-MB-231 cells. Moreover, PTX/miR124-NP showed significant antitumour efficiency and excellent safety in mice bearing MDA-MB-231 tumours.
Conclusion:
Based on these results, the codelivery of PTX and miR124 by the CaP/LNS nanosystem might be a promising therapeutic strategy for TNBC.
Insights
This study developed a novel nanosystem for the combined delivery of paclitaxel (PTX) and microRNA-124 (miR124) to treat triple-negative breast cancer (TNBC). The system demonstrated effective tumor targeting and synergistic anti-cancer effects, offering a promising new therapeutic strategy.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Oncology
Background:
- Triple-negative breast cancer (TNBC) is aggressive and lacks effective treatments.
- MicroRNA-124 (miR124) shows potential in inhibiting TNBC growth and enhancing paclitaxel (PTX) sensitivity.
- New therapeutic strategies are crucial for advanced TNBC.
Purpose of the Study:
- To develop a novel nanosystem for the co-delivery of PTX and miR124.
- To investigate the therapeutic efficacy and safety of this system for TNBC treatment.
Main Methods:
- Constructed a stepped cleavable calcium phosphate composite lipid nanosystem (CaP/LNS) for co-delivery.
- Designed the nanosystem for tumor microenvironment responsiveness, targeting CD44 receptors.
- Evaluated the synergistic anti-tumor effects and safety in vitro and in vivo.
Main Results:
- The CaP/LNS system effectively delivered PTX and miR124, showing tumor microenvironment responsiveness.
- The nanosystem facilitated cellular uptake and inhibited tumor metastasis by targeting CD44 and releasing o-HA.
- Synergistic anti-tumor effects were observed by reversing Epithelial-Mesenchymal Transition (EMT) in MDA-MB-231 cells.
- Significant anti-tumor efficiency and excellent safety were demonstrated in mice models.
Conclusions:
- The co-delivery of PTX and miR124 using the CaP/LNS nanosystem is a promising therapeutic strategy for TNBC.
- This approach offers a potential advancement in treating aggressive breast cancer subtypes.
Related Concept Videos
01:15Drugs that Stabilize Microtubules
01:10Drugs that Destabilize Microtubules