title: VEGF₁₂₁-conjugated mesoporous silica nanoparticle: a tumor targeted drug delivery system.
abstract: The vascular endothelial growth factor (VEGF)/VEGF receptor (VEGFR) signaling cascade plays a critical role in tumor angiogenesis and metastasis and has been correlated with several poorly prognostic cancers such as malignant gliomas. Although a number of anti-VEGFR therapies have been conceived, inefficient drug administration still limits their therapeutic efficacy and raises concerns of potential side effects. In the present work, we propose the use of uniform mesoporous silica nanoparticles (MSNs) for VEGFR targeted positron emission tomography imaging and delivery of the anti-VEGFR drug (i.e., sunitinib) in human glioblastoma (U87MG) bearing murine models. MSNs were synthesized, characterized and modified with polyethylene glycol, anti-VEGFR ligand VEGF121 and radioisotope (64)Cu, followed by extensive in vitro, in vivo and ex vivo studies. Our results demonstrated that a significantly higher amount of sunitinib could be delivered to the U87MG tumor by targeting VEGFR when compared with the non-targeted counterparts. The as-developed VEGF121-conjugated MSN could become another attractive nanoplatform for the design of future theranostic nanomedicine.
authors.affiliation: Materials Science Program, University of Wisconsin-Madison , Madison, Wisconsin 53705, United States.
authors.forename: Shreya
authors.initials: S
authors.lastname: Goel
authors.forename: Feng
authors.initials: F
authors.lastname: Chen
authors.forename: Hao
authors.initials: H
authors.lastname: Hong
authors.forename: Hector F
authors.initials: HF
authors.lastname: Valdovinos
authors.forename: Reinier
authors.initials: R
authors.lastname: Hernandez
authors.forename: Sixiang
authors.initials: S
authors.lastname: Shi
authors.forename: Todd E
authors.initials: TE
authors.lastname: Barnhart
authors.forename: Weibo
authors.initials: W
authors.lastname: Cai
mesh_terms: D000818:Animals; D016503:Drug Delivery Systems; D005909:Glioblastoma / Q000188:drug therapy* / Q000473:pathology; D005910:Glioma / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D007211:Indoles / Q000008:administration & dosage / Q000737:chemistry; D051379:Mice; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D011758:Pyrroles / Q000008:administration & dosage / Q000737:chemistry; D012822:Silicon Dioxide / Q000008:administration & dosage / Q000737:chemistry; D000077210:Sunitinib; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000037:antagonists & inhibitors / Q000235:genetics; D023041:Xenograft Model Antitumor Assays
chemical_list: D007211:Indoles; D011758:Pyrroles; D012822:Silicon Dioxide; D040281:Vascular Endothelial Growth Factor Receptor-1; D000077210:Sunitinib
keywords: VEGFR; drug delivery; mesoporous silica nanoparticle; positron emission tomography; vasculature targeting