Multi-targeting NGR-modified liposomes recognizing glioma tumor cells and vasculogenic mimicry for improving anti-glioma therapy

Abstract

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.

Long Non-Coding RNA HOXA-AS2 Regulates Malignant Glioma Behaviors and Vasculogenic Mimicry Formation via the MiR-373/EGFR Axis

“…Liu et al [5] demonstrated that VM-positive glioma patients have a poorer prognosis than patients with VM-negative gliomas. Ju et al [9], Huang et al [33], and Ying et al [34] proved that liposomes containing VM-targeting drugs improve anti-glioma therapy in orthotopic glioma-bearing nude mice. In agreement with the above findings, our in vitro and in vivo results showed that the destruction of VM formation by HOXA-AS2 knockdown impaired glioma malignancy.…”

A self-assembling nanomedicine of conjugated linoleic acid-paclitaxel conjugate (CLA-PTX) with higher drug loading and carrier-free characteristic

“…The in vitro cytotoxicity of CLA-PTX@PEG NPs was evaluated in B16-F10 cells, MDA-MB-231 cells and U87-MG cells using the sulfonylrhodamine B (SRB) assay182123. The half-maximal inhibitory concentration (IC 50 ) was calculated according to the dose-effect curves using GraphPad Prism 6 software.…”

Application of multifunctional targeting epirubicin liposomes in the treatment of non-small-cell lung cancer

“…8 Under the condition of hypoxia, tumor cells could directly form VM channels, thus facilitating tumor metastasis without the involvement of endothelial cells. [9][10][11] VM channels have been observed in a variety of malignant tumors including NSCLC and may provide sufficient blood perfusion for the rapid tumor growth. Increasing studies indicated that a poor prognosis in lung cancer patients was associated with the emergence of the VM channels.…”