Integrin-mediated targeting of drug delivery to irradiated tumor blood vessels
Integrin-mediated targeting of drug delivery to irradiated tumor blood vessels
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DOI：
10.1016/s1535-6108(02)00238-6
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发表时间：
2003-01-01
期刊：
影响因子：
50.3
通讯作者：
Clanton, J
中科院分区：
文献类型：
--
作者：
Hallahan, D;Geng, L;Clanton, J
这项研究的目的是将药物递送至辐射诱导的新抗原，其中包括肿瘤脉管系统内激活的受体。这些反应包括预先存在的蛋白质的翻译后变化，这些变化可以通过对携带辐射肿瘤的小鼠施用噬菌体展示肽库来发现。从受辐射的肿瘤中回收的噬菌体展示的肽包括氨基酸序列 RGDGSSV。该肽与肿瘤微血管系统内的整合素结合。受辐射肿瘤的免疫组织化学染色显示纤维蛋白原受体α(2b)β(3)整合素的积累。我们研究了辐射诱导的α(2b)β(3) 配体的肿瘤靶向效率。通过使用与纳米颗粒和脂质体缀合的α(2b)β(3)配体，放射性药物定位于受辐射的肿瘤。纤维蛋白原缀合的纳米粒子与辐射激活受体结合，消除肿瘤血流，并显着增加受辐射肿瘤的消退和生长延迟。放射引导的药物递送至肿瘤血管是靶向药物递送的新范例。
The objective of this study was to target drug delivery to radiation-induced neoantigens, which include activated receptors within the tumor vasculature. These responses include posttranslational changes in pre-existing proteins, which can be discovered by phage-displayed peptide libraries administered to mice bearing irradiated tumors. Phage-displayed peptides recovered from irradiated tumors included the amino acid sequence RGDGSSV. This peptide binds to integrins within the tumor microvasculature. Immunohistochemical staining of irradiated tumors showed accumulation of fibrinogen receptor alpha(2b)beta(3) integrin. We studied tumor targeting efficiency of ligands to radiation-induced alpha(2b)beta(3). Radiopharmaceuticals were localized to irradiated tumors by use of alpha(2b)beta(3) ligands conjugated to nanoparticles and liposomes. Fibrinogen-conjugated nanoparticles bind to the radiation-activated receptor, obliterate tumor blood flow, and significantly increase regression and growth delay in irradiated tumors. Radiation-guided drug delivery to tumor blood vessels is a novel paradigm for targeted drug delivery.