title: RGD peptide-conjugated selenium nanoparticles: antiangiogenesis by suppressing VEGF-VEGFR2-ERK/AKT pathway.
abstract: Angiogenesis is essential for tumorigenesis, progression and metastasis. Herein we described the synthesis of RGD peptide-decorated and doxorubicin-loaded selenium nanoparticles (RGD-NPs) targeting tumor vasculature to enhance the cellular uptake and antiangiogenic activities in vitro and in vivo. After internalization by receptor-mediated endocytosis, this nanosystem disassembled under acidic condition with the presence of lysozymes and cell lysate, leading to bioresponsive triggered drug release. Mechanistic investigation revealed that RGD-NPs inhibited angiogenesis through induction of apoptosis and cell cycle arrest in human umbilical vein endothelial cells (HUVECs) via suppression of VEGF-VEGFR2-ERK/AKT signaling axis by triggering ROS-mediated DNA damage. Additionally, RGD-NPs can inhibit MCF-7 tumor growth and angiogenesis in nude mice via down-regulation of VEGF-VEGFR2, effectively reduce the toxicity and prolong the blood circulation in vivo. Our results suggest that the strategy to use RGD-peptide functionalized SeNPs as carriers of anticancer drugs is an efficient way to achieve cancer-targeted antiangiogenesis synergism.
authors.affiliation: Department of Chemistry, Jinan University, Guangzhou, China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Fu
authors.affiliation: Department of Chemistry, Jinan University, Guangzhou, China.
authors.forename: Yahui
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Chemistry, Jinan University, Guangzhou, China. Electronic address: tlxlli@jnu.edu.cn.
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Chemistry, Jinan University, Guangzhou, China.
authors.forename: Haoqiang
authors.initials: H
authors.lastname: Lai
authors.affiliation: Department of Chemistry, Jinan University, Guangzhou, China.
authors.forename: Yanyu
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Chemistry, Jinan University, Guangzhou, China.
authors.forename: Lizhen
authors.initials: L
authors.lastname: He
authors.affiliation: Department of Chemistry, Jinan University, Guangzhou, China.
authors.forename: Wenjie
authors.initials: W
authors.lastname: Zheng
authors.affiliation: Department of Chemistry, Jinan University, Guangzhou, China. Electronic address: tchentf@jnu.edu.cn.
authors.forename: Tianfeng
authors.initials: T
authors.lastname: Chen
mesh_terms: D020533:Angiogenesis Inhibitors; D000818:Animals; D017209:Apoptosis; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D053758:Nanoparticles; D009369:Neoplasms / Q000628:therapy; D051057:Proto-Oncogene Proteins c-akt; D012643:Selenium; D042461:Vascular Endothelial Growth Factor A; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism*
chemical_list: D020533:Angiogenesis Inhibitors; D042461:Vascular Endothelial Growth Factor A; D040301:Vascular Endothelial Growth Factor Receptor-2; D051057:Proto-Oncogene Proteins c-akt; D012643:Selenium
keywords: Angiogenesis; Selenium nanoparticels; Targeted nanodrug delivery; VEGF