通过使用基因工程人类铁蛋白纳米粒子上呈现的多个肿瘤受体结合肽，通过主动肿瘤细胞靶向增强体内肿瘤检测。,Small

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通过使用基因工程人类铁蛋白纳米粒子上呈现的多个肿瘤受体结合肽，通过主动肿瘤细胞靶向增强体内肿瘤检测。
Small ( IF 13.0 ) Pub Date : 2016-06-30 , DOI: 10.1002/smll.201600917
Koo Chul Kwon ₁ , Ho Kyung Ko _{2,

3} , Jiyun Lee ₁ , Eun Jung Lee ₂ , Kwangmeyung Kim ₂ , Jeewon Lee ₁

Affiliation

人类铁蛋白重链纳米颗粒（hFTH）经过基因工程改造，可在其表面呈现肿瘤受体结合肽（亲和力和/或RGD衍生的环状肽，在此处称为4CRGD）。亲和体和4CRGD分别与人表皮生长因子受体I（EGFR）和人整联蛋白αvβ3特异性结合并牢固结合，它们在各种肿瘤细胞上均过表达。通过体外培养EGFR过表达的腺癌（MDA‐MB‐468）和整联蛋白过表达的胶质母细胞瘤细胞（U87MG），可以明确肿瘤细胞上的受体与工程hFTH上的受体结合肽之间的特异性相互作用对于活动性肿瘤至关重要单元格定位。用近红外荧光染料（Cy5.5）标记并向MDA-MB-468或U87MG荷瘤小鼠静脉内注射后，呈亲和体和4CRGD的一种或两种或两种肽形式存在的重组hFTHs可以成功地转移到肿瘤中并保留很长时间。特别地，与仅呈现亲和体或4CRGD的其他重组hFTH相比，同时呈现亲和体和4CRGD的重组hFTH显着增强了表达异源受体整联蛋白和EGFR的U87MG肿瘤的体内检测。像本研究中使用的affibody和4CRGD一样，也可以将其他多种肿瘤受体结合肽遗传引入hFTH表面，以利用异源受体主动靶向体内肿瘤。与仅提供亲和体或4CRGD的其他重组hFTHs相比，同时提供亲和体和4CRGD的重组hFTH显着增强了表达异源受体整联蛋白和EGFR的U87MG肿瘤的体内检测。像本研究中使用的affibody和4CRGD一样，也可以将其他多种肿瘤受体结合肽遗传引入hFTH表面，以利用异源受体主动靶向体内肿瘤。与仅提供亲和体或4CRGD的其他重组hFTHs相比，同时提供亲和体和4CRGD的重组hFTH显着增强了表达异源受体整联蛋白和EGFR的U87MG肿瘤的体内检测。像本研究中使用的affibody和4CRGD一样，也可以将其他多种肿瘤受体结合肽遗传引入hFTH表面，以利用异源受体主动靶向体内肿瘤。

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Enhanced In Vivo Tumor Detection by Active Tumor Cell Targeting Using Multiple Tumor Receptor‐Binding Peptides Presented on Genetically Engineered Human Ferritin Nanoparticles

Human ferritin heavy‐chain nanoparticle (hFTH) is genetically engineered to present tumor receptor‐binding peptides (affibody and/or RGD‐derived cyclic peptides, named 4CRGD here) on its surface. The affibody and 4CRGD specifically and strongly binds to human epidermal growth factor receptor I (EGFR) and human integrin αvβ3, respectively, which are overexpressed on various tumor cells. Through in vitro culture of EGFR‐overexpressing adenocarcinoma (MDA‐MB‐468) and integrin‐overexpressing glioblastoma cells (U87MG), it is clarified that specific interactions between receptors on tumor cells and receptor‐binding peptides on engineered hFTH is critical in active tumor cell targeting. After labeling with the near‐infrared fluorescence dye (Cy5.5) and intravenouse injection into MDA‐MB‐468 or U87MG tumor‐bearing mice, the recombinant hFTHs presenting either peptide or both of affibody and 4CRGD are successfully delivered to and retained in the tumor for a prolonged period of time. In particular, the recombinant hFTH presenting both affibody and 4CRGD notably enhances in vivo detection of U87MG tumors that express heterogeneous receptors, integrin and EGFR, compared to the other recombinant hFTHs presenting either affibody or 4CRGD only. Like affibody and 4CRGD used in this study, other multiple tumor receptor‐binding peptides can be also genetically introduced to the hFTH surface for actively targeting of in vivo tumors with heterogenous receptors.

更新日期：2016-06-30

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