Ultrasound activatable antiangiogenic sonosensitizer for VEGFR associated glioblastoma tumor models

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.

Automated summary

The study introduced a sunitinib-conjugated sonosensitizer to enhance anticancer efficacy by inhibiting VEGF-mediated antiangiogenesis and inducing cellular/tumor damage by ROS under ultrasound irradiation. The sonosensitizer showed good selectivity and cytotoxicity towards VEGFR-positive cells, providing an enhanced antitumor effect. This approach holds promise for optimizing anticancer performance by utilizing sonodynamic therapy in conjunction with antiangiogenics in various malignancies.