VEGF₁₂₁-Conjugated Mesoporous Silica Nanoparticle:\nA Tumor Targeted Drug Delivery System

Abstract

The\nvascular endothelial growth factor (VEGF)/VEGF receptor (VEGFR)\nsignaling cascade plays a critical role in tumor angiogenesis and\nmetastasis and has been correlated with several poorly prognostic\ncancers such as malignant gliomas. Although a number of anti-VEGFR\ntherapies have been conceived, inefficient drug administration still\nlimits their therapeutic efficacy and raises concerns of potential\nside effects. In the present work, we propose the use of uniform mesoporous\nsilica nanoparticles (MSNs) for VEGFR targeted positron emission tomography\nimaging and delivery of the anti-VEGFR drug (i.e., sunitinib) in human\nglioblastoma (U87MG) bearing murine models. MSNs were synthesized,\ncharacterized and modified with polyethylene glycol, anti-VEGFR ligand\nVEGF₁₂₁ and radioisotope ⁶⁴Cu, followed by extensive\nin vitro, in vivo and ex vivo studies. Our results demonstrated that\na significantly higher amount of sunitinib could be delivered to the\nU87MG tumor by targeting VEGFR when compared with the non-targeted\ncounterparts. The as-developed VEGF₁₂₁-conjugated MSN could\nbecome another attractive nanoplatform for the design of future theranostic\nnanomedicine.