Targeted disruption of tumor vasculature via polyphenol nanoparticles to improve brain cancer treatment
Fuyao Liu, Bin Peng, Miao Li, Junning Ma, Gang Deng, Shenqi Zhang, Wendy C. Sheu, Pan Zou, Haoan Wu, Jun Liu, Ann T. Chen, Farrah S. Mohammed, Jiangbing Zhou
Abstract
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.