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Updated: Sep 5, 2025
Author Spotlight: Exploring the Role of Ion Channels in Cancer: Characterization and Potential Treatment Approaches
Published on: June 16, 2023
Near-Infrared Light-Responsive Nanoinhibitors for Tumor Suppression through Targeting and Regulating Anion Channels
Chaoqun Li1, Sai Shi2, Dong Gao3
1School of Materials Science and Engineering, Hebei University of Technology, Tianjin 300130, P. R. China.
Abstract:
The gated state of anion channels is involved in the regulation of proliferation and migration of tumors. Specific regulators are urgently needed for efficacious cancer ablation. For this purpose, it is essential to understand the molecular mechanisms of interaction between the regulators and anion channels and apply this knowledge to regulate anion channels. Transmembrane 16A (TMEM16A) is the molecular basis of the calcium-activated chloride channels. It is an anion channel activated by Ca2+, and the inhibition of TMEM16A is associated with a decrease in tumorigenesis. Herein, we characterized a natural compound procyanidin (PC) as an efficacious and selective inhibitor of TMEM16A with an IC50 of 10.6 ± 0.6 μM. Our research revealed the precise sites (D383, R535, and E624) of electrostatic interactions between PC and TMEM16A. Near-infrared (NIR)-light-responsive photothermal conjugated polymer nanoparticles encapsulating PC (CPNs-PC) were established to remotely target and regulate the TMEM16A anion channel. Upon NIR irradiation, CPNs-PC downregulated the signaling pathway downstream of TMEM16A and arrested the cell cycle progression of cancer cells and improved the bioavailability of PC. The tumor inhibition ratio of CPNs-PC was superior to PC by 13.4%. Our findings enabled the development of a strategy to accurately and remotely regulate anion channels to promote tumor regression using NIR-light-responsive conjugated polymer nanoparticles containing specific inhibitors of TMEM16A.
Insights
Researchers identified procyanidin (PC) as a TMEM16A anion channel inhibitor. They developed nanoparticles (CPNs-PC) that use near-infrared light to target cancer cells, enhancing PC
Area of Science:
- Biochemistry
- Molecular Biology
- Nanotechnology
Background:
- Anion channels, particularly Transmembrane 16A (TMEM16A), regulate tumor cell proliferation and migration.
- Targeting TMEM16A offers a potential strategy for cancer ablation.
- Understanding TMEM16A regulation is crucial for developing effective cancer therapies.
Purpose of the Study:
- To characterize procyanidin (PC) as a TMEM16A inhibitor.
- To develop a targeted drug delivery system for PC using near-infrared (NIR) light-responsive nanoparticles.
- To evaluate the efficacy of PC-loaded nanoparticles in inhibiting cancer cell progression and tumor growth.
Main Methods:
- Characterization of procyanidin (PC) as a TMEM16A inhibitor using IC50 determination.
- Identification of specific interaction sites between PC and TMEM16A.
- Fabrication of NIR-light-responsive photothermal conjugated polymer nanoparticles encapsulating PC (CPNs-PC).
- In vitro and in vivo evaluation of CPNs-PC for cancer cell cycle arrest and tumor inhibition.
Main Results:
- Procyanidin (PC) was identified as a selective TMEM16A inhibitor with an IC50 of 10.6 ± 0.6 μM.
- Precise electrostatic interaction sites (D383, R535, E624) between PC and TMEM16A were determined.
- CPNs-PC demonstrated remote targeting and regulation of TMEM16A upon NIR irradiation.
- CPNs-PC effectively downregulated TMEM16A signaling, arrested cancer cell cycle, and improved PC bioavailability.
- CPNs-PC exhibited a superior tumor inhibition ratio (13.4% higher) compared to PC alone.
Conclusions:
- Procyanidin is an effective inhibitor of the TMEM16A anion channel.
- NIR-light-responsive nanoparticles provide a targeted and remotely controllable platform for delivering PC.
- This strategy offers a promising approach for cancer therapy by precisely regulating TMEM16A and promoting tumor regression.
