The effect of multistage nanovector targeting of VEGFR2 positive tumor endothelia on cell adhesion and local payload accumulation.
The effect of multistage nanovector targeting of VEGFR2 positive tumor endothelia on cell adhesion and local payload accumulation.
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DOI：
10.1016/j.biomaterials.2014.08.024
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发表时间：
2014-12
期刊：
影响因子：
14
通讯作者：
Tasciotti, Ennio
中科院分区：
文献类型：
--
作者：
Martinez, Jonathan O.;Evangelopoulos, Michael;Karun, Vivek;Shegog, Evan;Wang, Joshua A.;Boada, Christian;Liu, Xuewu;Ferrari, Mauro;Tasciotti, Ennio
关键词：
纳米载体是难溶性抗癌药物制剂的可行解决方案。它们在肿瘤实质中的生物蓄积主要是利用渗漏的新生血管系统的增强的渗透性和保留（EPR）效应来实现的。在本文中，我们证明了多级纳米载体（MSV）表现出快速的肿瘤归巢独立的EPR，依赖于颗粒的几何形状和表面粘附。通过研究过表达血管内皮生长因子受体2（VEGFR2）的内皮细胞，我们开发了能够优先靶向表达VEGFR2的肿瘤相关血管的MSV。静态和动态靶向显示，与抗VEGFR2抗体缀合的MSV显示出对表达VEGFR2的细胞的靶向效率增加超过4倍，同时表现出对对照细胞的最小粘附。此外，VEGFR2缀合使MSV在乳腺肿瘤靶向和模型有效载荷的递送方面显著增加，同时减少它们在肝脏中的积累。用抗VEGFR2抗体的表面功能化提供了对肿瘤血管内皮的增强的亲和力，这促进了由MSV释放的报告分子的增强的粘附和致瘤性积累。
Nanovectors are a viable solution to the formulation of poorly soluble anticancer drugs. Their bioaccumulation in the tumor parenchyma is mainly achieved exploiting the enhanced permeability and retention (EPR) effect of the leaky neovasculature. In this paper we demonstrate that multistage nanovectors (MSV) exhibit rapid tumoritropic homing independent of EPR, relying on particle geometry and surface adhesion. By studying endothelial cells overexpressing vascular endothelial growth factor receptor-2 (VEGFR2), we developed MSV able to preferentially target VEGFR2 expressing tumor-associated vessels. Static and dynamic targeting revealed that MSV conjugated with anti-VEGFR2 antibodies displayed greater than a 4-fold increase in targeting efficiency towards VEGFR2 expressing cells while exhibiting minimal adherence to control cells. Additionally, VEGFR2 conjugation bestowed MSV with a significant increase in breast tumor targeting and in the delivery of a model payload while decreasing their accumulation in the liver. Surface functionalization with an anti-VEGFR2 antibody provided enhanced affinity towards the tumor vascular endothelium, which promoted enhanced adhesion and tumoritropic accumulation of a reporter molecule released by the MSV.
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DOI：
10.1016/j.jconrel.2014.01.003
发表时间：
2014-03-28
期刊：
Journal of controlled release : official journal of the Controlled Release Society
影响因子：
--
作者：
Hou H;Nieto A;Ma F;Freeman WR;Sailor MJ;Cheng L
通讯作者：
Cheng L
DOI：
10.1016/j.jconrel.2012.07.010
发表时间：
2012-12-10
期刊：
Journal of controlled release : official journal of the Controlled Release Society
影响因子：
--
作者：
Kwon IK;Lee SC;Han B;Park K
通讯作者：
Park K
影响因子：
14
作者：
Martinez, Jonathan O.;Chiappini, Ciro;Tasciotti, Ennio
通讯作者：
Tasciotti, Ennio
影响因子：
14
作者：
Decuzzi, Paolo;Ferrari, Mauro
通讯作者：
Ferrari, Mauro
影响因子：
3.5
作者：
Lee, Sei-Young;Ferrari, Mauro;Decuzzi, Paolo
通讯作者：
Decuzzi, Paolo