KORCHAGINA Anna Serbsky Scientific Center of Forensic and Social Psychiatry

Anti-VEGFR2 Nanogels as a Delivery System of Therapeutic Agents to the Brain Tumor Cells

Co-authors NUKOLOVA N.V., SHEIN S.A., ABAKUMOVA T.O., GURINA O.I., CHEKHONIN V.P.

Angiogenesis plays a crucial role in tumor progression. Vascular endothelial growth factor (VEGF) is believed to be the most important regulation factor of tumor vascular supply. VEGFR-2 is the main transducer of VEGF signaling in tumor-associated angiogenesis. Accordingly, a variety of therapeutic approaches aimed at VEGF/VEGFR2 signaling axis. One of these methods can be targeted drug delivery of therapeutics agents using polymeric nanocarriers modified with anti-VEGFR2 antibodies targeting of tumor cells. This approach could on the one hand, improve delivery efficacy of therapeutic agents. On the other hand, it can reduce broad range of adverse side effects of chemotherapy treatment. Our purpose was to investigate the ability of synthesized nanogels conjugated with anti-VEGFR2 antibodies accumulate in tumor cells. In this work we prepared poly(ethylene glycol)170-b-poly(methacrylic acid)180 nanogels conjugated with anti-VEGFR2 antibodies. Nanogels are negatively charged, stable with narrow polydispersity. Covalent attachment of anti-VEGFR2 antibodies to nanogels has shown 60 % affinity of initial. Anti-VEGFR2-nanogels accumulation was specific and more effective to the VEGFR2-positive U-87 MG and C6 cell lines than in case of untargeted nanogels or nanogels conjugated with nonspecific antibodies. Overall, the study indicates that anti-VEGFR2 antibodies conjugated with nanogels can be used to increase efficacy of delivery therapeutic agents to the tumor cells. ACKNOWLEDGEMENTS: This work was supported by a grant from Russian scientific foundation (RSCF) № 14-15-00698.

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