Near-Infrared Light Regulation of Tumor PI3K/Akt Signaling Pathway for Enhancing Cancer Cell Apoptosis through Conjugated Polymer Nanoparticles
Benkai Bao, Dong Gao, Ning Li, Manman Wu, Chengfen Xing
Abstract
Calmodulin (CaM), as a calcium binding protein involved in the signal pathways of many life activities such as cell proliferation and apoptosis, can be regulated with the near-infrared (NIR) light-based photothermal conversion. Here, we build a conjugated polymer nanoparticle (CPNs-C) by assembling polypyrrole dione and dipalmitoyl phosphatidylethanolamine-polyethylene glycol-maleimide with a calmodulin antibody modified on the surface, which is NIR light-responsive for photothermally inducing apoptosis of cancer cells. Under near-infrared light irradiation, protein kinase B (Akt) and phosphatidylinositol 3-kinase, which bind to CaM, reduce the degree of phosphorylation due to the photothermal effect of CPNs-C, thus inhibiting the recruitment of Akt on the cell membrane. Therefore, the phosphorylation of GSK-3β downstream of the signaling pathway is reduced, and the phosphorylation of FoxO3a is enhanced, which can promote apoptosis of cancer cells. Compared with the photothermal effect of traditional CPNs, CPNs-C exhibits higher efficiency to regulate signaling pathways to promote cancer cells toward apoptosis. This strategy of utilizing NIR light to regulate the tumor apoptotic signaling pathway provides an effective way to enhance cancer cell apoptosis with high efficiency.