期刊
ACS APPLIED MATERIALS & INTERFACES
卷 6, 期 23, 页码 21677-21685出版社
AMER CHEMICAL SOC
DOI: 10.1021/am506849p
关键词
VEGFR; mesoporous silica nanoparticle; drug delivery; vasculature targeting; positron emission tomography
资金
- University of Wisconsin-Madison
- National Institutes of Health [NIBIB/NCI 1R01CA169365, P30CA014520, 5T32GM08349]
- Department of Defense [W81XWH-11-1-0644]
- American Cancer Society [125246-RSG-13-099-01-CCE]
- National Science Foundation [DGE-1256259]
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 VEGF(121) and radioisotope Cu-64, 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 VEGF(121)-conjugated MSN could become another attractive nanoplatform for the design of future theranostic nanomedicine.
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