cRGD-directed, NIR-responsive and robust AuNR/PEG-PCL hybrid nanoparticles for targeted chemotherapy of glioblastoma in vivo.

Abstract

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 0.2 W/cm2, due to photothermally induced phase transition of PCL regime. MTT assays showed that the antitumor activity of cRGD-HN-DOX in αvβ3 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.

• Authors: Yinan Zhong, Chao Wang, Ru Cheng, Liang Cheng, Fenghua Meng, Zhuang Liu, Zhiyuan Zhong
• Journal: Journal of controlled release : official journal of the Controlled Release Society (J Control Release) Vol. 195 Pg. 63-71 (Dec 10 2014) ISSN: 1873-4995 [Electronic] Netherlands
• PMID: 25108151 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier B.V. All rights reserved.

Chemical References

• Antineoplastic Agents
• Drug Carriers
• Oligopeptides
• Polyesters
• polycaprolactone
• Polyethylene Glycols
• Gold
• arginyl-glycyl-aspartic acid
• Doxorubicin

Topics

• Animals
• Antineoplastic Agents (administration & dosage, blood, chemistry, pharmacokinetics)
• Cell Line, Tumor
• Doxorubicin (administration & dosage, blood, chemistry, pharmacokinetics)
• Drug Carriers (administration & dosage, chemistry)
• Glioblastoma (drug therapy, metabolism)
• Gold (chemistry)
• Humans
• Mice, Nude
• Nanoparticles (administration & dosage, chemistry)
• Nanotubes (chemistry)
• Oligopeptides (administration & dosage, chemistry)
• Polyesters (chemistry)
• Polyethylene Glycols (chemistry)
• Tissue Distribution
• Xenograft Model Antitumor Assays