Multivalent viral capsids with internal cargo for fibrin imaging.
Multivalent viral capsids with internal cargo for fibrin imaging.
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DOI：
10.1371/journal.pone.0100678
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Francis MB
中科院分区：
文献类型：
--
作者：
Obermeyer AC;Capehart SL;Jarman JB;Francis MB
血栓形成是许多心血管综合征的原因，并且是危及生命的疾病（例如心肌梗塞和中风）的重要因素。血栓靶向显像剂能够提供有关病理性血栓的分子信息，有可能改善血栓相关疾病的检测、风险分层和治疗。纳米载体是分子成像剂开发的一个有前途的平台，因为它们可以被修改为具有外部靶向配体和内部功能性货物。在这项工作中，我们报告了化学功能化噬菌体 MS2 衣壳的合成和使用，作为基于生物分子的纳米粒子用于纤维蛋白成像。使用氧化偶联反应对衣壳进行修饰，将约 90 个拷贝的纤维蛋白靶向肽缀合到每个蛋白质壳的外部。多价靶向衣壳结合纤维蛋白的能力首先通过确定对凝血酶介导的凝块形成的影响来证明。修饰的衣壳优于游离肽，并且在比单独的单体肽低十倍以上的有效浓度下抑制凝块形成。在衣壳内表面安装近红外荧光团使得能够光学检测与纤维蛋白凝块的结合。靶向衣壳与纤维蛋白结合，表现出比对照非靶向 MS2 纳米剂更高的信号背景比。衣壳的体外评估表明，靶向纤维蛋白的 MS2 衣壳可用作血栓的递送剂，用于诊断或治疗应用。
Thrombosis is the cause of many cardiovascular syndromes and is a significant contributor to life-threatening diseases, such as myocardial infarction and stroke. Thrombus targeted imaging agents have the capability to provide molecular information about pathological clots, potentially improving detection, risk stratification, and therapy of thrombosis-related diseases. Nanocarriers are a promising platform for the development of molecular imaging agents as they can be modified to have external targeting ligands and internal functional cargo. In this work, we report the synthesis and use of chemically functionalized bacteriophage MS2 capsids as biomolecule-based nanoparticles for fibrin imaging. The capsids were modified using an oxidative coupling reaction, conjugating ∼90 copies of a fibrin targeting peptide to the exterior of each protein shell. The ability of the multivalent, targeted capsids to bind fibrin was first demonstrated by determining the impact on thrombin-mediated clot formation. The modified capsids out-performed the free peptides and were shown to inhibit clot formation at effective concentrations over ten-fold lower than the monomeric peptide alone. The installation of near-infrared fluorophores on the interior surface of the capsids enabled optical detection of binding to fibrin clots. The targeted capsids bound to fibrin, exhibiting higher signal-to-background than control, non-targeted MS2-based nanoagents. The in vitro assessment of the capsids suggests that fibrin-targeted MS2 capsids could be used as delivery agents to thrombi for diagnostic or therapeutic applications.
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影响因子：
17.1
作者：
Ashley CE;Carnes EC;Phillips GK;Durfee PN;Buley MD;Lino CA;Padilla DP;Phillips B;Carter MB;Willman CL;Brinker CJ;Caldeira Jdo C;Chackerian B;Wharton W;Peabody DS
通讯作者：
Peabody DS
影响因子：
4.7
作者：
Kolodziej, Andrew F.;Nair, Shrikumar A.;Graham, Philip;McMurry, Thomas J.;Ladner, Robert C.;Wescott, Charles;Sexton, Daniel J.;Caravan, Peter
通讯作者：
Caravan, Peter
影响因子：
5.6
作者：
Binz, HK;Stumpp, MT;Plückthun, A
通讯作者：
Plückthun, A
影响因子：
15
作者：
Hooker, JM;Kovacs, EW;Francis, MB
通讯作者：
Francis, MB
影响因子：
--
作者：
LATALLO, ZS;ALKJAERSIG, N;SHERRY, S
通讯作者：
SHERRY, S