RGD peptide-conjugated selenium nanoparticles: antiangiogenesis by suppressing VEGF-VEGFR2-ERK/AKT pathway

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• 作者：Xiaoyan Fu ; PhD¹ ; Yahui Yang ; MSc¹ ; Xiaoling Li ; PhD ; ^{tlxlli@jnu.edu.cn" class="auth_mail" title="E-mail the corresponding author} ; Haoqiang Lai ; MSc ; Yanyu Huang ; PhD ; Lizhen He ; PhD ; Wenjie Zheng ; PhD ; Tianfeng Chen ; PhD ; ^{tchentf@jnu.edu.cn" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Angiogenesis ; Selenium nanoparticels ; Targeted nanodrug delivery ; VEGF
• 刊名：Nanomedicine: Nanotechnology, Biology and Medicine
• 出版年：2016
• 出版时间：August 2016
• 年：2016
• 卷：12
• 期：6
• 页码：1627-1639
• 全文大小：2761 K

文摘

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.