Ultrasound activatable antiangiogenic sonosensitizer for VEGFR associated glioblastoma tumor models

Abstract

Abstract Angiogenic signaling pathway is a major contributing factor in cancer recurrence and progression, which can cause significantly reduced treatment outcomes, especially in the oxygen‐dependent photo‐ and sonodynamic therapies. VEGF and its receptor (VEGFR) play a crucial role in angiogenesis progression; precisely, upregulated VEGF signaling is mainly associated with angiogenesis progression in many types of cancers. Herein, we report a sunitinib‐conjugated sonosensitizer (TK‐RB: tyrosine kinase‐rose bengal) to enhance the anticancer efficacy through VEGF inhibition‐mediated antiangiogenesis in conjunction with cellular/tumor damage by ROS generated under ultrasound irradiation. TK‐RB reveals good selectivity and cytotoxicity toward VEGFR‐positive cells (U87MG) over VEGFR‐negative cells (MCF‐7). The fluorescent imaging analysis in vivo/ex vivo and the tumor growth investigation in nude mice with U87MG glioblastoma tumor xenografts demonstrate that rose bengal having tyrosine kinase inhibitor (TK‐RB) provides an enhanced antitumor effect. The current strategy will make a great contribution to optimizing anticancer performance by utilizing sonodynamic therapy together with antiangiogenics in several different malignancies.

Keywords

• antiangiogenesis
• glioblastoma
• sonodynamic therapy
• VEGFR blockage