Journal
JOURNAL OF CONTROLLED RELEASE
Volume 195, Issue -, Pages 63-71Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jconrel.2014.07.054
Keywords
cRGD; Gold nanorods; Biodegradable nanoparticles; Doxorubicin; NIR-sensitive; Glioblastoma
Funding
- National Natural Science Foundation of China [NSFC 51173126, 51273139, 51103093, 51273137, 51003070, 81261120557]
- National Science Fund for Distinguished Young Scholars [NSFC 51225302]
- Ph.D. Programs Foundation of Ministry of Education of China [20133201110005]
- Priority Academic Program Development of Jiangsu Higher Education Institutions [PAPD 233200613]
- Innovative Graduate Research Program of Jiangsu Province [CXZZ13_0805]
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cRGD-directed, NIR-responsive and robust AuNR/PEG-PCL hybrid nanoparticles (cRGD-HNs) were designed and developed for targeted chemotherapy of human glioma xenografts in mice. As expected, cRGD-HNs had excellent colloidal stability. The in vitro release studies showed that drug release from DOX-loaded cRGD-HNs (cRGD-HN-DOX) was minimal under physiological conditions but markedly accelerated upon NIR irradiation at a low power density of 0.2W/cm(2), due to photothermally induced phase transition of PCL regime. MTT assays showed that the antitumor activity of cRGD-HN-DOX in alpha(v)beta(3) integrin over-expressed human glioblastoma U87MG cells was greatly boosted by mild NIR irradiation, which was significantly more potent than non-targeting HN-DOX counterpart under otherwise the same conditions and was comparable or superior to free DOX, supporting receptor-mediated endocytosis mechanism. The in vivo pharmacokinetics studies showed that cRGD-HN-DOX had much longer circulation time than free DOX. The in vivo imaging and biodistribution studies revealed that cRGD-HN-DOX could actively target human U87MG glioma xenograft in nude mice. The therapeutic studies in human U87MG glioma xenografts exhibited that cRGD-HN-DOX in combination with NIR irradiation completely inhibited tumor growth and possessed much lower side effects than free DOX. The Kaplan-Meier survival curves showed that all mice treated with cRGD-HN-DOX plus NIR irradiation survived over an experimental period of 48 days while control groups treated with PBS, cRGD-HN-DOX, cRGD-HNs with NIR irradiation, free DOX, or HN-DOX with NIR irradiation (non-targeting control) had short life spans of 15-40 days. Ligand-directed AuNR/PEG-PCL hybrid nanoparticles with evident tumor-targetability as well as superior spatiotemporal and rate control over drug release have emerged as an appealing platform for cancer chemotherapy in vivo. (C) 2014 Elsevier B.V. All rights reserved.
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