Targeting to tumor necrotic regions with biotinylated antibody and streptavidin modified liposomes.
Targeting to tumor necrotic regions with biotinylated antibody and streptavidin modified liposomes.
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DOI：
10.1016/j.jconrel.2007.10.016
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发表时间：
2008-02
期刊：
影响因子：
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通讯作者：
Hong Pan;Limei Han;Wei Chen;M. Yao;Weiyue Lu
中科院分区：
文献类型：
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作者：
Hong Pan;Limei Han;Wei Chen;M. Yao;Weiyue Lu
肿瘤坏死治疗（TNT）是使用单克隆抗体（如嵌合TNT-3单克隆抗体（chTNT-3））开发的，可靶向实体瘤，这些单克隆抗体可结合位于肿瘤坏死区域的退化细胞。由于生物素化的chTNT-3显示出比未修饰的chTNT-3更短的循环时间和更多的肿瘤摄取，我们设计了两步预靶向方法，包括施用生物素化的chTNT-3和24小时后施用包封多柔比星（DOX）的链霉亲和素修饰的脂质体以将DOX递送到肿瘤部位。通过ELISA证实生物素化的chTNT-3的免疫反应性的保留。在Sprague+IBM-Dawley大鼠体内，两步预靶向法中总DOX的生物半衰期比游离DOX长，但比空间稳定脂质体短。两步预靶向方案在生物分布研究中显示出良好的肿瘤靶向性和渐进性。在施用装载DOX的脂质体后4小时和24小时，观察到两步预靶向方法的最高DOX水平。在荷H460肿瘤的Balb/c裸小鼠中，第二次治疗后3天观察到最佳抗肿瘤效果。这些结果表明，两步预靶向方案可能是一种新的形式，提供抗癌药物的肿瘤坏死区。
Tumor Necrosis Treatment (TNT) was developed to target solid tumors using monoclonal antibodies such as the chimeric TNT-3 monoclonal antibody (chTNT-3), which bind to degenerating cells located in necrotic regions of tumors. Since biotinylated chTNT-3 showed shorter circulating time and more uptakes in tumors than unmodified chTNT-3, we designed the two-step pretargeting approach composed of administering biotinylated chTNT-3 and 24 h later administering streptavidin modified liposomes encapsulating doxorubicin (DOX) to deliver DOX to the tumor site. The preservation of immunoreactivity of biotinylated chTNT-3 was confirmed by ELISA. The biological half-life of total DOX in two-step pretargeting approach was longer than that of free DOX but shorter than that of sterically stabilized liposomes in Sprague+IBM-Dawley rats. The two-step pretargeting approach regimen displayed good tumor targeting with a gradual process in biodistribution study. At 4 h and 24 h after administering DOX-loaded liposomes a highest DOX level of the two-step pretargeting approach was observed. The best antitumor efficacy was observed 3 days after the second treatment in Balb/c nude mice bearing H460 tumors. These results suggested the two-step pretargeting approach regimen may be a new form for delivering anticancer drugs to tumor necrotic regions.