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Title: Nanoencapsulated bevacizumab inhibits glioblastoma vascularization via intratumoral VEGF trapping

Flavia Sousa

Universidade do Porto, Portugal

Biography

Flávia Sousa graduated from Instituto Superior de Ciências da Saúde-Norte in Porto (Portugal) with MS in Pharmaceutical Sciences. She is finishing her PhD in Biomedical Sciences in the Nanomedicines and Translational Drug Delivery group at i3S/INEB, University of Porto. Recently, she joined at Instituto Superior de Ciências da Saúde-Norte in Porto as invited professor. Her research interests are related to nanomedicine field, drug delivery systems, structural characterization of proteins and antibodies, intracellular delivery of antibodies through polymeric nanoparticles, in vitro cell-based studies and in vivo models related to cancer and angiogenesis, mainly in the glioblastoma field. She is author/co-author of 17 peer-reviews articles, 5 book chapters and 6 presentations at scientific meetings. During her PhD, she did collaborations with different universities/laboratories, such as, INL, Aalborg University, Northeastern University, etc. In 2018, she won a Fulbright grant to do part of her PhD at Northeastern University as a visiting scholar and she won a Kinam Park 2018 Student Award to the Controlled Release Society in New York City. She was also elected as representative of PhD students at i3s, University of Porto. Since 2018, Flávia is a member of the Young Committee of Spanish Portuguese Chapter of the Controlled Release Society and first vowel of the Fiscal Council of Portuguese American Postgraduate Society.

Abstract

Glioblastoma multiforme (GBM) is the most aggressive malignant brain tumor, being the median survival time of patients at around 15 months after disease diagnosis. GBM has the constant need of vascularization, making this tumor one of the most vascularized and invasive solid tumors. Bevacizumab, an anti-VEGF monoclonal antibody, was approved by FDA to be used as a single agent for patients with GBM. Despite good results in the clinical trials, the low probability of bevacizumab in crossing the BBB limits its CNS accessibility and does not allow an improvement in the overall patient survival. Therefore, an alternative to improve the efficacy of GBM treatment is highly needed and might be achieved by the combination of nanotechnology through controlled release nanosystems. In this study, bevacizumab-loaded PLGA NP were successfully developed as an alternative to cross effectively BBB, accomplishing a better therapy. No significant differences were also found by BrdU and ELISA assay for anti-proliferative and anti-VEGF properties between free and encapsulated bevacizumab, demonstrating the success of encapsulation. In vivo efficacy of bevacizumab-loaded PLGA NP was evaluated using a glioma zebrafish model to study the neoangiogenesis and tumor growth through the injection of GBM cancer cells. In vivo results showed a significant decrease in tumor area just for the bevacizumab-loaded PLGA NP group. Trying to understand the molecular mechanism behind the efficacy of nanoparticles, a cellular uptake in both cell lines was done to study the internalization of bevacizumab and its effect on VEGF secretion. A significant increase in the number of bevacizumab positive cells and a decrease in the number of VEGF producing cells was obtained for the bevacizumab-loaded PLGA NP group. These last results demonstrated that bevacizumab-loaded PLGA NP might cause a disorder in VEGF signaling pathway, being an efficient alternative to deliver intracellularly monoclonal antibodies.
Audience take away:
• The audience will be able to know what polymeric nanoparticles can allow an intracellular delivery of monoclonal antibodies, being a benefit for further diseases
• Intracellular delivery of monoclonal antibodies is a new paradigm for the pharmaceutical world, bringing new formulations to treat cancer, especially glioblastoma.
• A higher angiogenic effect was achieved with the internalization of bevacizumab, open a new window for antiangiogenic therapeutic strategies