Melanoma and lymphocyte cell-specific targeting incorporated into a heat shock protein cage architecture
Melanoma and lymphocyte cell-specific targeting incorporated into a heat shock protein cage architecture
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DOI：
10.1016/j.chembiol.2005.11.007
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发表时间：
2006-02-01
影响因子：
--
通讯作者：
Douglas, T
中科院分区：
文献类型：
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作者：
Flenniken, ML;Willits, DA;Douglas, T
蛋白质笼，包括病毒衣壳、铁蛋白和热休克蛋白（Hsps），可以作为生物医学应用的纳米容器。它们是具有遗传和化学延展性的平台，具有作为治疗和显像剂输送系统的潜力。在这里，使用遗传和化学策略将细胞特异性靶向詹氏甲烷球菌的 Hsp 笼。肿瘤脉管系统靶向肽被整合到 Hsp 笼的外表面。该蛋白笼与表达α(v)β(3)整合素的细胞结合。细胞向性也是通过将抗 CD4 抗体缀合到 Hsp 笼的外部而赋予的。这些 Ab-Hsp 笼状缀合物特异性结合 CD4(+) 细胞。蛋白质笼有可能同时整合多种功能，包括细胞特异性靶向、成像和治疗剂递送。我们展示了将成像和细胞特异性靶向这两种功能同时整合到 Hsp 蛋白笼上。
Protein cages, including viral capsids, ferritins, and heat shock proteins (Hsps), can serve as nanocontainers for biomedical applications. They are genetically and chemically malleable platforms, with potential as therapeutic and imaging agent delivery systems. Here, both genetic and chemical strategies were used to impart cell-specific targeting to the Hsp cage from Methanococcus jannaschii. A tumor vasculature targeting peptide was incorporated onto the exterior surface of the Hsp cage. This protein cage bound to alpha(v)beta(3) integrin-expressing cells. Cellular tropism was also imparted by conjugating anti-CD4 antibodies to the exterior of Hsp cages. These Ab-Hsp cage conjugates specifically bound to CD4(+) cells. Protein cages have the potential to simultaneously incorporate multiple functionalities, including cell-specific targeting, imaging, and therapeutic agent delivery. We demonstrate the simultaneous incorporation of two functionalities, imaging and cell-specific targeting, onto the Hsp protein cage.