An intein-mediated site-specific click conjugation strategy for improved tumor targeting of nanoparticle systems.
An intein-mediated site-specific click conjugation strategy for improved tumor targeting of nanoparticle systems.
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DOI：
10.1002/smll.201001095
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发表时间：
2010-11-05
期刊：
影响因子：
13.3
通讯作者：
Tsourkas, Andrew
中科院分区：
文献类型：
--
作者：
Elias, Drew R.;Cheng, Zhiliang;Tsourkas, Andrew
修饰和直接靶向纳米颗粒载体的能力大大增加了它们在诊断和治疗研究中的适用性。通常，对纳米颗粒的靶向至关重要的是靶向配体与试剂表面的生物缀合。虽然近年来生物缀合技术已经稳步改进，但该领域仍然受到低效缀合反应和/或缺乏位点特异性偶联的困扰。为了克服这些限制，点击化学和表达蛋白连接（EPL）相结合，以产生高效的位点特异性反应。这种新的EPL-点击缀合策略被应用于产生用HER 2/neu受体体标记的超顺磁性氧化铁纳米颗粒（SPIO）。这些HER 2 ‐SPIO纳米颗粒在体外细胞研究和鼠肿瘤模型中均被证明具有高度效力和受体特异性。此外，当将EPL点击衍生的HER 2-SPIO与使用其他流行的生物缀合方法用HER 2抗体标记的SPIO进行比较时，它们在细胞结合后的对比度增强方面产生了统计学显著的改善。EPL-点击系统也成功地扩展到其他纳米颗粒平台（即，脂质体和树枝状聚合物）强调了该方法的多功能性。
The ability to modify and directly target nanoparticulate carriers has greatly increased their applicability in diagnostic and therapeutic studies. Generally essential to the targeting of nanoparticles is the bioconjugation of targeting ligands to the agent's surface. While bioconjugation techniques have steadily improved in recent years, the field is still plagued with inefficient conjugations reactions and/or the lack of site‐specific coupling. To overcome these limitations, click chemistry and expressed protein ligation (EPL) are combined to produce a highly efficient, site‐specific reaction. This new EPL–click conjugation strategy is applied to create superparamagnetic iron oxide nanoparticles (SPIO) labeled with HER2/neu affibodies. These HER2‐SPIO nanoparticles prove to be highly potent and receptor‐specific in both in vitro cell studies and murine tumor models. Moreover, when EPL–click‐derived HER2‐SPIO are compared with SPIO that had been labeled with HER2 affibodies using other popular bioconjugation methods, they produce a statistically significant improvement in contrast enhancement upon cell binding. The EPL–click system is also successfully extended to other nanoparticle platforms (i.e., liposomes and dendrimers) highlighting the versatility of the approach.
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