Related Experiment Video
Updated: Jul 2, 2025
Studying Triple Negative Breast Cancer Using Orthotopic Breast Cancer Model
Published on: March 20, 2020
Combined Photosensitive Gene Therapy Effective Against Triple-Negative Breast Cancer in Mice Model
Yixue Hu1, Dongna Wang2, Tianyu Zhang2
1College of Life Science, Nanjing Normal University, Nanjing, People's Republic of China.
Introduction:
Tumor hypoxia and invasion present significant challenges for the efficacy of photodynamic therapy (PDT) in triple-negative breast cancer (TNBC). This study developed a mitochondrial targeting strategy that combined PDT and gene therapy to promote each other and address the challenges.
Methods:
The positively charged amphiphilic material triphenylphosphine-tocopherol polyethylene glycol succinate (TPP-TPGS, TPS) and the photosensitizer chloride e6 (Ce6) formed TPS@Ce6 nanoparticles (NPs) by hydrophobic interaction. They electrostatically condensed microRNA-34a (miR-34a) to form stable TPS@Ce6/miRNA NPs.
Results:
Firstly, Ce6 disrupted the lysosomal membrane, followed by successful delivery of miR-34a by TPS@Ce6/miRNA NPs. Meanwhile, miR-34a reduced ROS depletion and further enhanced the effectiveness of PDT. Consequently, the mutual promotion between PDT and gene therapy led to enhanced anti-tumor effects. Furthermore, the TPS@Ce6/miRNA NPs promoted apoptosis by down-regulating Caspase-3 and inhibited tumor cell migration and invasion by down-regulating N-Cadherin. In addition, in vitro and in vivo experiments demonstrated that the TPS@Ce6/miRNA NPs achieved excellent anti-tumor effects. These findings highlighted the enhanced anticancer effects and reduced migration of tumor cells through the synergistic effects of PDT and gene therapy.
Conclusion:
Taken together, the targeted co-delivery of Ce6 and miR-34a will facilitate the application of photodynamic and genic nanomedicine in the treatment of aggressive tumors, particularly TNBC.
Insights
This study combined photodynamic therapy (PDT) and gene therapy using nanoparticles to treat triple-negative breast cancer (TNBC). The approach enhanced anti-tumor effects and reduced cancer cell migration.
Area of Science:
- Biomedical Engineering
- Nanomedicine
- Cancer Therapy
Background:
- Triple-negative breast cancer (TNBC) poses challenges for photodynamic therapy (PDT) due to tumor hypoxia and invasion.
- Developing novel therapeutic strategies is crucial for improving TNBC treatment efficacy.
Purpose of the Study:
- To develop a mitochondrial targeting strategy combining PDT and gene therapy for enhanced anti-tumor effects in TNBC.
- To investigate the synergistic effects of PDT and microRNA-34a (miR-34a) delivery.
Main Methods:
- Fabrication of TPS@Ce6/miRNA nanoparticles (NPs) encapsulating photosensitizer (Ce6) and miR-34a.
- Utilizing a triphenylphosphine-tocopherol polyethylene glycol succinate (TPP-TPGS) based nanocarrier for mitochondrial targeting.
- Evaluating the therapeutic efficacy in vitro and in vivo.
Main Results:
- TPS@Ce6/miRNA NPs successfully delivered Ce6 and miR-34a, disrupting lysosomes and enhancing PDT efficacy.
- Co-delivery of Ce6 and miR-34a demonstrated synergistic anti-tumor effects, promoting apoptosis and inhibiting migration.
- Achieved significant anti-tumor effects in both in vitro and in vivo models.
Conclusions:
- The developed nanomedicine strategy effectively overcomes challenges in TNBC treatment.
- Targeted co-delivery of Ce6 and miR-34a shows promise for aggressive tumor treatment, particularly TNBC.
