Photothermal Conjugated Polymer Nanoparticles for Suppressing Breast Tumor Growth by Regulating TRPA1 Ion Channels
Boying Li1, Shuxi Ren2, Dong Gao2
1School of Materials Science and Engineering, Hebei University of Technology, Tianjin, 300401, P. R. China.
Abstract:
Cancer cells survive by relying on oxidative stress defense against the accumulation of reactive oxygen species (ROS) during tumor formation. ROS-sensitive TRPA1 ion channels are overexpressed in breast cancer cells and induce a large influx of Ca2+ which upregulates the anti-apoptotic pathway to lead breast cancer cells to produce oxidative stress defense and enhance the resistance to ROS related chemotherapy. Targeting and inhibiting the TRPA1 ion channels are critical for breaking down the oxidative stress defense system and overcoming cellular resistance. Here, near-infrared (NIR) light-responsive conjugated polymer nanoparticles are designed and prepared to promote apoptosis of breast cancer cells, reduce cell drug resistance and suppress tumor growth through the remote and precise regulation of TRPA1 ion channels. Upon 808 nm laser irradiation, the nanoparticles block the formation of Ca2+ /CaM complex and regulate the content of MCL-1 protein. Especially, the nanoparticles overcome drug resistance of cancer cells, therefore accelerating apoptosis of cancer cells and suppressing tumor growth in mice. Compared with carboplatin, the volume of tumor induced by NPs-H decreases by 54.1%. This work provides a strategy to disrupt the oxidative stress defense system and downregulate the antiapoptotic signaling pathway in cancer cells.
Insights
New nanoparticles target cancer
Area of Science:
- Oncology
- Biomedical Engineering
- Nanotechnology
Background:
- Cancer cells utilize oxidative stress defense mechanisms to survive, involving reactive oxygen species (ROS) and TRPA1 ion channels.
- Overexpressed TRPA1 channels in breast cancer cells facilitate calcium influx, promoting anti-apoptotic pathways and chemoresistance.
- Inhibiting TRPA1 channels is crucial for disrupting cancer's oxidative stress defense and overcoming drug resistance.
Purpose of the Study:
- To design and synthesize near-infrared (NIR) light-responsive conjugated polymer nanoparticles for targeted breast cancer therapy.
- To investigate the nanoparticles' ability to regulate TRPA1 ion channels, induce apoptosis, and overcome drug resistance in cancer cells.
- To evaluate the therapeutic efficacy of these nanoparticles in suppressing tumor growth in vivo.
Main Methods:
- Development of NIR light-responsive conjugated polymer nanoparticles.
- In vitro studies on breast cancer cells to assess apoptosis induction and drug resistance modulation.
- In vivo studies using mouse models to evaluate tumor suppression efficacy compared to chemotherapy.
Main Results:
- The designed nanoparticles, upon 808 nm laser irradiation, effectively block Ca2+/CaM complex formation and regulate MCL-1 protein.
- Nanoparticles demonstrated significant promotion of cancer cell apoptosis and overcoming of drug resistance.
- In vivo studies showed a 54.1% decrease in tumor volume compared to carboplatin treatment, indicating potent tumor suppression.
Conclusions:
- NIR-responsive nanoparticles offer a novel strategy to disrupt cancer's oxidative stress defense system.
- Targeting TRPA1 ion channels with these nanoparticles effectively downregulates anti-apoptotic signaling, enhancing therapeutic outcomes.
- This approach presents a promising method for overcoming breast cancer chemoresistance and suppressing tumor growth.
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