Despite being effective for many other solid
tumors, traditional anti-angiogenic
therapy has been shown to be insufficient for the treatment of
malignant glioma. Here, we report the development of
polyphenol nanoparticles (NPs), which not only inhibit the formation of new vessels but also enable targeted disruption of the existing
tumor vasculature. The NPs are synthesized through a combinatory
iron-coordination and
polymer-stabilization approach, which allows for high drug loading and intrinsic
tumor vessel targeting. We study a lead NP consisting of
quercetin and find that the NP after
intravenous administration preferentially binds to VEGFR2, which is overexpressed in
tumor vasculature. We demonstrate that the binding is mediated by
quercetin, and the interaction of NPs with VEGFR2 leads to disruption of the existing
tumor vasculature and inhibition of new vessel development. As a result, systemic treatment with the NPs effectively inhibits
tumor growth and increases drug delivery to
tumors.