Chemically activatable viral capsid functionalized for cancer targeting.
Chemically activatable viral capsid functionalized for cancer targeting.
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DOI：
10.2217/nnm.15.207
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发表时间：
2016-02
期刊：
影响因子：
--
通讯作者：
Cheng RH
中科院分区：
文献类型：
--
作者：
Chen CC;Xing L;Stark M;Ou T;Holla P;Xiao K;Kamita SG;Hammock BD;Lam K;Cheng RH
使用经过修饰的戊型肝炎病毒的病毒样纳米颗粒来设计一种治疗诊断胶囊，以显示乳腺癌细胞靶向功能组（LXY30）。五个表面暴露的残基突变为半胱氨酸，以允许通过硫醇选择性连接与马来酰亚胺连接的化学基团缀合。然后将工程化的病毒样纳米粒子与乳腺癌识别配体 LXY30 和胺偶联近红外荧光染料共价结合。检查了 LXY30-HEV VLP 与乳腺癌细胞系的结合和进入，以及小鼠体内肿瘤对乳腺癌组织的靶向性。这种工程化的病毒样纳米颗粒不仅靶向癌细胞，而且由于抗体结合位点的表位破坏，对天然戊型肝炎病毒抗体表现出免疫沉默。这些结果表明，基于高度稳定的病毒样纳米颗粒的表面修饰，可以生产出适用于癌症诊断和治疗的治疗诊断胶囊。
To design a theranostic capsule using the virus-like nanoparticle of the hepatitis E virus modified to display breast cancer cell targeting functional group (LXY30). Five surface-exposed residues were mutated to cysteine to allow conjugation to maleimide-linked chemical groups via thiol-selective linkages. Engineered virus-like nanoparticles were then covalently conjugated to a breast cancer recognized ligand, LXY30 and an amine-coupled near-infrared fluorescence dye. LXY30-HEV VLP was checked for its binding and entry to a breast cancer cell line and for tumor targeting in vivo to breast cancer tissue in mice. The engineered virus-like nanoparticle not only targeted cancer cells, but also appeared immune silent to native hepatitis E virus antibodies due to epitope disruption at the antibody-binding site. These results demonstrate the production of a theranostic capsule suitable for cancer diagnostics and therapeutics based on surface modification of a highly stable virus-like nanoparticle.