Abstract
Objective: This study aimed to evaluate the efficacy of the improved nanoscaled delivery system for doxorubicin (Dox) based on angiopep (ANG)-2 modified graphene oxide (GO), the so-called ANG-Dox-GO, in suppressing the growth and and metastasis of glioma cells.Results: Modification of GO by angiopep-2 significantly increased the cellular uptake of Dox. In addition, ANG-Dox-GO treatment of U87 MG cells significantly inhibited cell viability, decreased clone number, cell migration and invasion andinduced cell apoptosis, with superior efficiency over that of Dox-GO and free Dox. Similar results were observed in in vivo experiments—tumor size and weight of glioma xenograft mice were obviously decreased after treatments with ANG-Dox-GO, Dox-GO and Dox, respectively, as compared with control group, and the efficiency was the highest in ANG-Dox-GO, followed by Dox-Go and Dox.Conclusions: ANG-Dox-GO exhibited superior anti-glioma effects over Dox-GO both in vitro and in vivo experiments.Methods: The morphology of ANG-Dox-GO was analyzed by UV visible absorption spectroscopy and atomic force microscopy and its in vitro cellular uptake was measured using confocal imaging analysis. The antitumor effects of GO, unbound Dox, Dox-GO and ANG-Dox-GO were evaluated by MTT assay, colony-forming assay, cell apoptosis assay and Transwell assay in U87 malignant glioma (MG) cells.
Highlights
Glioma is the most common form of primary malignant tumor that occurs in the central nervous system
These results indicated that the modification by angiopep-2 increased the cellular uptake of the delivery system
Compared with control cells, cell treated with Graphene oxide (GO) had little-to-no effects on cell proliferation, apoptosis and migration in U87 malignant glioma (MG) cells; ANG-Dox-GO treatment significantly inhibited cell viability, decreased clone number, suppressed cell migration and invasion, as well as induced cell apoptosis, the efficiency was followed by Dox-GO and free Dox treatment
Summary
Glioma is the most common form of primary malignant tumor that occurs in the central nervous system. It originates in the neurogenic ectoderm and is, characterized by high rates of metastasis, recurrence and mortality [1]. The conventional and effective therapeutic options for glioma are primarily sophisticated surgical resection, followed by chemoradiation and immunotherapy [2, 3]. It is essential to uncover the underlying molecular mechanism of glioma as well as develop effective treatment options. Nanomaterials have shown bright promises in detection and treatment of cancers by exerting various targeted roles including imaging, immunodetection, chemotherapy, radiotherapy and immunotherapy [4]. Several studies have proved anti-tumor effects of GO as a tumor targeting drug carrier [8,9,10]
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