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

被引:113
作者
Goel, Shreya [1 ]
Chen, Feng [2 ]
Hong, Hao [2 ]
Valdovinos, Hector F. [3 ]
Hernandez, Reninier [3 ]
Shi, Sixiang [1 ]
Barnhart, Todd E. [3 ]
Cai, Weibo [1 ,2 ,3 ,4 ]
机构
[1] Univ Wisconsin, Mat Sci Program, Madison, WI 53705 USA
[2] Univ Wisconsin, Dept Radiol, Madison, WI 53705 USA
[3] Univ Wisconsin, Dept Med Phys, Madison, WI 53705 USA
[4] Univ Wisconsin, Carbone Canc Ctr, Madison, WI 53705 USA
基金
美国国家科学基金会; 美国国家卫生研究院;
关键词
VEGFR; mesoporous silica nanoparticle; drug delivery; vasculature targeting; positron emission tomography; ENDOTHELIAL GROWTH-FACTOR; POSITRON-EMISSION-TOMOGRAPHY; FACTOR RECEPTOR; MAGNETIC-RESONANCE; VASCULATURE; SUNITINIB; INHIBITION; EXPRESSION; THERAPY; MODEL;
D O I
10.1021/am506849p
中图分类号
TB3 [工程材料学];
学科分类号
0805 ; 080502 ;
摘要
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.
引用
收藏
页码:21677 / 21685
页数:9
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