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

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• 作者：Shreya Goel ; Feng Chen ; Hao Hong ; Hector F. Valdovinos ; Reinier Hernandez ; Sixiang Shi ; Todd E. Barnhart ; Weibo Cai
• 刊名：ACS Applied Materials & Interfaces
• 出版年：2014
• 出版时间：December 10, 2014
• 年：2014
• 卷：6
• 期：23
• 页码：21677-21685
• 全文大小：432K
• ISSN：1944-8252

文摘

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 ⁶⁴Cu, 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.

Keywords:

VEGFR; mesoporous silica nanoparticle; drug delivery; vasculature targeting; positron emission tomography