RGD peptide functionalized and reconstituted high-density lipoprotein nanoparticles as a versatile and multimodal tumor targeting molecular imaging probe
RGD peptide functionalized and reconstituted high-density lipoprotein nanoparticles as a versatile and multimodal tumor targeting molecular imaging probe
复制标题
DOI：
10.1096/fj.09-139865
复制
发表时间：
2010-06-01
期刊：
影响因子：
4.8
通讯作者：
Fayad, Zahi A.
中科院分区：
文献类型：
--
作者：
Chen, Wei;Jarzyna, Peter A.;Fayad, Zahi A.
高密度脂蛋白（HDL）是一种内源性纳米颗粒，可将脂肪转运至全身，并能够将胆固醇从血管壁中的粥样硬化转移至肝脏。在本研究中，我们利用HDL作为多模式纳米颗粒平台，通过非特异性积累和特异性结合血管生成激活的血管进行肿瘤靶向和成像。我们用两亲性钆螯合物和荧光染料重建HDL（rHDL）。为了靶向血管生成内皮细胞，用α v β 3-整联蛋白特异性RGD肽（rHDL-RGD）功能化rHDL。将非特异性RAD肽缀合至rHDL纳米颗粒作为对照（rHDL-RAD）。在体外观察到，所有3种纳米颗粒均被巨噬细胞吞噬，而α v β 3-整联蛋白特异性rHDL-RGD纳米颗粒优先被内皮细胞摄取。使用近红外（NIR）和MR成像在体内评价小鼠肿瘤中纳米颗粒的摄取。所有纳米颗粒在肿瘤中积累，但如通过NIR成像观察到的具有非常不同的积累/结合动力学。此外，共聚焦显微镜显示rHDL-RGD与肿瘤内皮细胞相关，而rHDL和rHDL-RAD纳米颗粒主要存在于间质中。这项研究证明了将HDL从其天然靶点重新路由到肿瘤血管的能力，以及其对肿瘤相关过程的多模式成像的潜力。陈伟，Jarzyna，P. A.，货车蒂尔堡，G. A. F.、阮，弗吉尼亚州，科莫德，D。P.，Klink，A.，Griffioen，A. W.，兰多夫，G. J.，Fisher，E.一、Mulder，W. J.M.，Fayad，Z. A. RGD肽功能化和重组高密度脂蛋白纳米颗粒作为多功能和多模式肿瘤靶向分子成像探针。FASEB J.24，1689-1699（2010）。www.fasebj.org
High density lipoprotein (HDL), an endogenous nanoparticle, transports fat throughout the body and is capable of transferring cholesterol from atheroma in the vessel wall to the liver. In the present study, we utilized HDL as a multimodal nanoparticle platform for tumor targeting and imaging via nonspecific accumulation and specific binding to angiogenically activated blood vessels. We reconstituted HDL (rHDL) with amphiphilic gadolinium chelates and fluorescent dyes. To target angiogenic endothelial cells, rHDL was functionalized with alpha v beta 3-integrin-specific RGD peptides (rHDL-RGD). Nonspecific RAD peptides were conjugated to rHDL nanoparticles as a control (rHDL-RAD). It was observed in vitro that all 3 nanoparticles were phagocytosed by macrophages, while alpha v beta 3-integrin-specific rHDL-RGD nanoparticles were preferentially taken up by endothelial cells. The uptake of nanoparticles in mouse tumors was evaluated in vivo using near infrared (NIR) and MR imaging. All nanoparticles accumulated in tumors but with very different accumulation/binding kinetics as observed by NIR imaging. Moreover, confocal microscopy revealed rHDL-RGD to be associated with tumor endothelial cells, while rHDL and rHDL-RAD nanoparticles were mainly found in the interstitial space. This study demonstrates the ability to reroute HDL from its natural targets to tumor blood vessels and its potential for multimodal imaging of tumor-associated processes.-Chen, W., Jarzyna, P. A., van Tilborg, G. A. F., Nguyen, V. A., Cormode, D. P., Klink, A., Griffioen, A. W., Randolph, G. J., Fisher, E. A., Mulder, W. J. M., Fayad, Z. A. RGD peptide functionalized and reconstituted high-density lipoprotein nanoparticles as a versatile and multimodal tumor targeting molecular imaging probe. FASEB J. 24, 1689-1699 (2010). www.fasebj.org