一种用于寡聚物肿瘤靶向递送的纳米颗粒。
A nanoparticle for tumor targeted delivery of oligomers.
作者信息
Liu Xinrong, Wang Yi, Hnatowich Donald J
机构信息
Division of Nuclear Medicine, Department of Radiology, University of Massachusetts Medical School, Worcester, MA, USA.
出版信息
Methods Mol Biol. 2011;764:91-105. doi: 10.1007/978-1-61779-188-8_6.
The tissue-specific delivery nanoparticle consists of an antisense oligomer, a cell-penetrating peptide, and an antitumor antibody, each biotinylated and each linked via streptavidin. Within the nanoparticle, the antibody provides specific targeted delivery and binding to the target cells, the peptide improves cell membrane transport, and the antisense oligomer, through its mRNA-binding ability, provides specific retention of the radioactivity in the target cell nucleus. The use of streptavidin as linker eliminates the need for covalent conjugation without appearing to interfere with the in vitro and in vivo properties of each component. The delivery nanoparticle is under development to improve tumor targeting with unlabeled siRNAs as well as radiolabeled antisense oligomers in a variety of tumor types. The anti-HER2 Trastuzumab (Herceptin) antibody, the tat peptide, and a radiolabeled antisense oligomer against the RIα mRNA have been used in this report as an example.
组织特异性递送纳米颗粒由反义寡聚物、细胞穿透肽和抗肿瘤抗体组成，它们均被生物素化且通过链霉亲和素连接。在纳米颗粒内部，抗体提供特异性靶向递送并与靶细胞结合，肽改善细胞膜转运，而反义寡聚物通过其mRNA结合能力，使放射性在靶细胞核中实现特异性保留。使用链霉亲和素作为连接物无需共价缀合，且似乎不会干扰各组分的体外和体内特性。目前正在研发这种递送纳米颗粒，以改善多种肿瘤类型中未标记的小干扰RNA以及放射性标记的反义寡聚物的肿瘤靶向性。本报告中以抗HER2曲妥珠单抗（赫赛汀）抗体、tat肽和针对RIα mRNA的放射性标记反义寡聚物为例进行了说明。
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