Near-Infrared Light-Responsive Nanoinhibitors for Tumor Suppression through Targeting and Regulating Anion Channels.

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.

• Authors: Chaoqun Li, Sai Shi, Dong Gao, Boying Li, Guoqiang Song, Yafei Chen, Hailong An, Chengfen Xing
• Journal: ACS applied materials & interfaces (ACS Appl Mater Interfaces) Vol. 14 Issue 28 Pg. 31715-31726 (Jul 20 2022) ISSN: 1944-8252 [Electronic] United States
• PMID: 35798541 (Publication Type: Journal Article)

Chemical References

• Anions
• Anoctamin-1
• Chloride Channels
• Polymers
• Calcium

Topics

• Anions
• Anoctamin-1 (metabolism)
• Calcium (metabolism)
• Chloride Channels (metabolism)
• Polymers (metabolism)
• Signal Transduction