Dual Activation of Calcium Channels Using Near-Infrared Responsive Conjugated Oligomer Nanoparticles for Precise Regulation of Blood Glucose Homeostasis
Ning Li, Chen Li, Boying Li, Chaoqun Li, Qi Zhao, Zhongming Huang, Yue Shu, Xiongwei Qu, Baiqi Wang, Shengliang Li, Chengfen Xing
Abstract
The rarity of efficient tools with spatiotemporal resolution and biocompatibility capabilities remains a major challenge for further progress and application of signaling manipulation. Herein, biomimetic conjugated oligomeric nanoparticles (CM-CONs) were developed to precisely modulate blood glucose homeostasis via the two-pronged activation of calcium channels. Under near-infrared (NIR) laser irradiation, CM-CONs efficiently generate local heat and reactive oxygen species (ROS), thereby simultaneously activating thermosensitive transient receptor potential V1 (TRPV1) and ROS-sensitive transient receptor potential A1 (TRPA1) calcium channels in small intestinal endocrine cells. The activation of the channels mediates inward calcium flow and then promotes glucagon-like peptide (GLP-1) secretion. Both in vitro and in vivo studies indicate that CM-CONs effectively regulate glucose homeostasis in diabetic model mice upon NIR light irradiation. This work develops a two-pronged attack strategy for accurately controlling blood glucose homeostasis, holding great prospects in the treatment for diabetes.