title: Rational Design of Cancer-Targeted Benzoselenadiazole by RGD Peptide Functionalization for Cancer Theranostics.
abstract: A cancer-targeted conjugate of the selenadiazole derivative BSeC (benzo[1,2,5] selenadiazole-5-carboxylic acid) with RGD peptide as targeting molecule and PEI (polyethylenimine) as a linker is rationally designed and synthesized in the present study. The results show that RGD-PEI-BSeC forms nanoparticles in aqueous solution with a core-shell nanostructure and high stability under physiological conditions. This rational design effectively enhances the selective cellular uptake and cellular retention of BSeC in human glioma cells, and increases its selectivity between cancer and normal cells. The nanoparticles enter the cells through receptor-mediated endocytosis via clathrin-mediated and nystatin-dependent lipid raft-mediated pathways. Internalized nanoparticles trigger glioma cell apoptosis by activation of ROS-mediated p53 phosphorylation. Therefore, this study provides a strategy for the rational design of selenium-containing cancer-targeted theranostics.
authors.affiliation: Department of Chemistry, Jinan University, Guangzhou, 510632, China.
authors.forename: Liye
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Chemistry, Jinan University, Guangzhou, 510632, China.
authors.forename: Wenying
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Chemistry, Jinan University, Guangzhou, 510632, China.
authors.forename: Yanyu
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Chemistry, Jinan University, Guangzhou, 510632, China.
authors.forename: Yangliang
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Chemistry, Jinan University, Guangzhou, 510632, China.
authors.forename: Tianfeng
authors.initials: T
authors.lastname: Chen
mesh_terms: D001393:Azoles / Q000737:chemistry / Q000627:therapeutic use*; D015195:Drug Design; D004705:Endocytosis; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy; D009842:Oligopeptides / Q000737:chemistry*; D066244:Proton Magnetic Resonance Spectroscopy; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D000068936:Theranostic Nanomedicine
chemical_list: D001393:Azoles; D009842:Oligopeptides; D017382:Reactive Oxygen Species; C047981:arginyl-glycyl-aspartic acid
keywords: apoptosis; cancer theranotics; modification; nanoparticles; selectivity