Multi-targeting NGR-modified liposomes recognizing glioma tumor cells and vasculogenic mimicry for improving anti-glioma therapy.
Like the anti-angiogenic strategy, anti-vascular mimicry is considered as a novel targeting strategy for glioma. In the present study, we used NGR as a targeting ligand and prepared NGR-modified liposomes containing combretastatin A4 (NGR-SSL-CA4) in order to evaluate their potential targeting of glioma tumor cells and vasculogenic mimicry (VM) formed by glioma cells as well as their anti-VM activity in mice with glioma tumor cells. NGR-SSL-CA4 was prepared by a thin-film hydration method. The in vitro targeting of U87-MG (human glioma tumor cells) by NGR-modified liposomes was evaluated. The in vivo targeting activity of NGR-modified liposomes was tested in U87-MG orthotopic tumor-bearing nude mice. The anti-VM activity of NGR-SSL-CA4 was also investigated in vitro and in vivo. The targeting activity of the NGR-modified liposomes was demonstrated by in vitro flow cytometry and in vivo biodistribution. The in vitro anti-VM activity of NGR-SSL-CA4 was indicated in a series of cell migration and VM channel experiments. NGR-SSL-CA4 produced very marked anti-tumor and anti-VM activity in U87-MG orthotopic tumor-bearing mice in vivo. Overall, the NGR-SSL-CA4 has great potential in the multi-targeting therapy of glioma involving U87-MG cells, and the VM formed by U87-MG cells as well as endothelial cells producing anti-U87-MG cells, and anti-VM formed by U87-MG cells as well as anti-endothelial cell activity.
Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.|Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
Dan
D
Huang
Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.|Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
Shuang
S
Zhang
Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.|Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
Ting
T
Zhong
Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.|Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
Wei
W
Ren
Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.|Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
Xin
X
Yao
Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.|Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
Yang
Y
Guo
Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.|Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
Xiao-Chuan
XC
Duan
Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
Yi-Fan
YF
Yin
Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
Shu-Shi
SS
Zhang
Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.|Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
Xuan
X
Zhang
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D001921:Brain / Q000098:blood supply / Q000000981:diagnostic imaging / Q000473:pathology; D001932:Brain Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D042783:Endothelial Cells / Q000187:drug effects / Q000473:pathology; D005434:Flow Cytometry; D005910:Glioma / Q000000981:diagnostic imaging / Q000188:drug therapy*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008081:Liposomes / Q000737:chemistry*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D000071069:Multiple Chronic Conditions; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D009842:Oligopeptides / Q000737:chemistry; D061848:Optical Imaging; D013267:Stilbenes / Q000627:therapeutic use*; D014018:Tissue Distribution; D023041:Xenograft Model Antitumor Assays
D000972:Antineoplastic Agents, Phytogenic; D008081:Liposomes; D009842:Oligopeptides; D013267:Stilbenes; C058728:fosbretabulin
NGR; anti-tumor activity; combretastatin A4; glioma; vascular mimicry