期刊
NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE
卷 12, 期 6, 页码 1627-1639出版社
ELSEVIER
DOI: 10.1016/j.nano.2016.01.012
关键词
Angiogenesis; Selenium nanoparticels; Targeted nanodrug delivery; VEGF
资金
- National High Technology Research and Development Program of China (863 Program) [SS2014AA020538]
- National High-level Personnel of Special Support Program
- Science Foundation for Distinguished Young Scholars of Guangdong Province [S2013050014667]
- Natural Science Foundation of China
- Foundation for High-level Talents in Higher Education of Guangdong
- YangFan Innovative & Entepreneurial Research Team Project [201312H05]
- Guangdong Special Support Program
- Guangdong Frontier and Key Technological Innovation Special Funds
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. (C) 2016 Elsevier Inc. All rights reserved.
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