Synergistic Effect of Immunoliposomal Gemcitabine and Bevacizumab in Glioblastoma Stem Cell-Targeted Therapy
Glioblastoma stem cells have been shown to confer chemoresistance and radioresistance, leading to angiogenesis and the recurrence of tumors in glioblastoma multiforme. Combination therapy targeting glioblastoma stem cells and anti-angiogenesis has been a focus of treatment strategies
because of the enhanced efficacy achieved by dual inhibition of tumor proliferation and nutrient delivery. In this study, glioblastoma stem cells and glioblastoma stem cell-induced angiogenesis in glioblastoma multiforme were challenged by combined treatment with anti-CD133 monoclonal antibody
conjugated liposomes encapsulating gemcitabine and bevacizumab. Both liposomal encapsulation and conjugation of an anti-CD133 antibody significantly enhanced the cytotoxicity of gemcitabine toward glioblastoma stem cells in vitro. Moreover, combined treatment with this gemcitabine formulation
and bevacizumab significantly inhibited tube formation, migration, and proliferation of endothelial cells in vitro. The antitumor efficacy of immunoliposomal gemcitabine and bevacizumab combination therapy in a xenograft model was significantly greater than that of monotherapy, presumably
reflecting the enhanced effects on glioblastoma stem cells themselves and glioblastoma stem cell-induced angiogenesis caused by synergistic interactions between the two drugs. Moreover, combination therapy prolonged the mean survival time of xenografted mice. Taken altogether, our results
suggest that combined therapy with immunoliposomal gemcitabine and bevacizumab shows promise for the treatment of glioblastoma multiforme.
Keywords: BEVACIZUMAB; GEMCITABINE; GLIOBLASTOMA STEM CELLS; LIPOSOMES; SYNERGISM; TARGETING
Document Type: Research Article
Publication date: 01 October 2015
- Journal of Biomedical Nanotechnology (JBN) is a peer-reviewed multidisciplinary journal providing broad coverage in all research areas focused on the applications of nanotechnology in medicine, drug delivery systems, infectious disease, biomedical sciences, biotechnology, and all other related fields of life sciences.
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