In vivo delivery of antisense MORF oligomer by MORF/carrier streptavidin nanoparticles.
In vivo delivery of antisense MORF oligomer by MORF/carrier streptavidin nanoparticles.
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DOI：
10.1089/cbr.2009.0624
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发表时间：
2009-10
影响因子：
3.4
通讯作者：
Yi Wang;Xinrong Liu;Kayoko Nakamura;Ling Chen;M. Rusckowski;D. Hnatowich
中科院分区：
文献类型：
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作者：
Yi Wang;Xinrong Liu;Kayoko Nakamura;Ling Chen;M. Rusckowski;D. Hnatowich
寡聚体的肿瘤靶向作用在很大程度上受到药代动力学和细胞膜转运障碍的限制。在这篇文章中，我们描述了使用的交付纳米粒子，其中链霉亲和素作为一个方便的桥梁之间的生物素化的寡聚体和生物素化的细胞膜穿透肽，以提高交付的反义磷酰二胺吗啉代（MORF）寡聚体在体内。将具有与RI α mRNA反义的碱基序列的生物素化（99 m）Tc-放射性标记的MORF寡聚体及其有义对照分别掺入纳米颗粒中，沿着生物素化达特或聚精氨酸载体。将链霉亲和素纳米颗粒静脉内施用至携带SUM 149乳腺肿瘤异种移植物的正常小鼠和裸鼠。与裸的相比，当作为纳米颗粒施用时，生物分布显示放射性标记的MORF的正常组织水平高得多，与反义或有义或达特或聚精氨酸无关。与相应的有义对照纳米颗粒相比，观察到两种反义纳米颗粒的统计学显著更高的积累，与历史裸对照相比，沿着高得多的肿瘤积累。该研究提供了证据表明，链霉亲和素纳米颗粒内的反义寡聚体的体内功能不受阻碍，因此，M0 RF/链霉亲和素/载体纳米颗粒可适用于反义M0 RF和其它寡聚体的体内肿瘤递送。
Tumor targeting by oligomers is largely limited by the pharmacokinetics and cell-membrane transport obstacles. In this article, we describe the use of a delivery nanoparticle, in which streptavidin served as a convenient bridge between a biotinylated oligomer and a biotinylated cell-membrane-penetrating peptide, to improve the delivery of an antisense phosphorodiamidate morpholino (MORF) oligomer in vivo. A biotinylated (99m)Tc-radiolabeled MORF oligomer with a base sequence antisense to the RIalpha mRNA and its sense control were incorporated separately into nanoparticles, along with biotinylated tat or polyarginine carrier. The streptavidin nanoparticles were administrated intravenously to both normal and nude mice bearing SUM149 breast tumor xenografts. The biodistributions showed much higher normal tissue levels for the radiolabeled MORFs, independent of antisense or sense or tat or polyarginine, when administered as the nanoparticles, compared to naked. A statistically significant higher accumulation of both antisense nanoparticles, compared to the respective sense control nanoparticles, was observed, along with much higher tumor accumulations, compared to historical naked controls. This study has provided evidence that the in vivo function of an antisense oligomer within the streptavidin nanoparticle is not impeded, and, as such, the MORF/streptavidin/carrier nanoparticles may be suitable for in vivo tumor delivery of antisense MORF and other oligomers.