Anti-VEGFR2-labeled enzyme-immobilized metal-organic frameworks for tumor vasculature targeted catalytic therapy.

ABSTRACT

Tumor vasculature-targeting therapy either using angiogenesis inhibitors or vascular disrupting agents offers an important new avenue for cancer therapy. In this work, a tumor-specific catalytic nanomedicine for enhanced tumor ablation accompanied with tumor vasculature disruption and angiogenesis inhibition was developed through a cascade reaction with enzyme glucose oxidase (GOD) modified on Fe-based metal organic framework (Fe-MOF) coupled with anti-VEGFR2.The GOD enzyme could catalyze the intratumoral glucose decomposition to trigger tumor starvation and yet provide abundant hydrogen peroxide as the substrate for Fenton-like reaction catalyzed by Fe-MOF to produce sufficient highly toxic hydroxyl radicals for enhanced chemodynamic therapy and instantly attacked tumor vascular endothelial cells to destroy the existing vasculature, while the anti-VEGFR2 antibody guided the nanohybrids to target blood vessels and block the VEGF-VEGFR2 connection to prevent angiogenesis. Both in vitro and in vivo results demonstrated the smart nanohybrids could cause the tumor cell apoptosis and vasculature disruption, and exhibited enhanced tumor regression in A549 xenograft tumor-bearing mice model. This study suggested that synergistic targeting tumor growth and its vasculature network would be more promising for curing solid tumors. STATEMENT OF SIGNIFICANCE: Cooperative destruction of tumor cells and tumor vasculature offers a potential avenue for cancer therapy. Under this premise, a tumor-specific catalytic nanomedicine for enhanced tumor ablation accompanied with tumor vasculature disruption and new angiogenesis inhibition was developed through a cascade reaction with glucose oxidase modified on the surface of iron-based metal organic framework coupled with VEGFR2 antibody. The resulting data demonstrated that a therapeutic regimen targeting tumor growth as well as its vasculature with both existing vasculature disruption and neovasculature inhibition would be more potential for complete eradication of tumors.