Antibody-targeted paclitaxel loaded nanoparticles for the treatment of CD20(+) B-cell lymphoma.
Antibody-targeted paclitaxel loaded nanoparticles for the treatment of CD20(+) B-cell lymphoma.
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DOI：
10.1038/srep45682
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发表时间：
2017-04-05
影响因子：
4.6
通讯作者：
Markovic SN
中科院分区：
文献类型：
--
作者：
Nevala WK;Butterfield JT;Sutor SL;Knauer DJ;Markovic SN
我们开发了一种纳米抗体靶向化疗(NatC)递送策略，其中肿瘤特异性和临床相关抗体(美妥昔单抗、抗CD20)非共价结合到NAB-紫杉醇(ABX)的白蛋白支架上。我们定义了当两种药物结合时形成的纳米颗粒(AR160)。新制备的NatC在体外保留了ABX的细胞毒性和利妥昔单抗的CD20亲和力。我们使用肽图/Biacore方法描述了AR160中ABX和利妥昔单抗的结合特征。基于流动的方法，包括ImageStream和纳米颗粒跟踪，被用来在体外表征AR160颗粒。利用人B细胞淋巴瘤的小鼠模型来测试AR160治疗的体内疗效，这表明改善肿瘤靶向性(生物分布)是AR160治疗优于ABX或单独利妥昔单抗的最可能机制。这些数据表明，通过对现有抗癌药物进行轻微修改，可以提供一种新的平台，显著提高治疗效果。
We developed a nano-antibody targeted chemotherapy (nATC) delivery strategy in which tumor specific and clinically relevant antibodies (rituximab, anti-CD20) are non-covalently bound to the albumin scaffold of nab-paclitaxel (ABX). We define the nanoparticle formed when the 2 drugs are bound (AR160). The newly created nATC retains the cytotoxicity of ABX and CD20 affinity of rituximab in vitro. We describe the binding characteristics of the ABX and rituximab in AR160 using peptide mapping/Biacore approach. Flow-based methods, including ImageStream and nanoparticle tracking, were used to characterize the AR160 particles in vitro. A mouse model of human B-cell lymphoma was utilized to test in vivo efficacy of AR160 therapy, which suggested improved tumor targeting (biodistribution) as the most likely mechanism of AR160 therapeutic superiority over ABX or rituximab alone. These data suggest a novel platform for nATC delivery using a slight modification of existing cancer drugs with significantly improved treatment efficacy.