Limiting the protein corona: A successful strategy for in vivo active targeting of anti-HER2 nanobody-functionalized nanostars
Limiting the protein corona: A successful strategy for in vivo active targeting of anti-HER2 nanobody-functionalized nanostars
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DOI：
10.1016/j.biomaterials.2017.01.007
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发表时间：
2017-04-01
期刊：
影响因子：
14
通讯作者：
Himmelreich, Uwe
中科院分区：
文献类型：
--
作者：
D'Hollander, Antoine;Jans, Hilde;Himmelreich, Uwe
金纳米粒子通过主动靶向肿瘤细胞，作为抗癌治疗诊断剂具有很大的前景。由于这种潜力在体外实验中得到了大量的支持，我们对复杂的体内生物系统中相互作用的理解和控制有限，阻碍了有效的应用。当这些纳米颗粒暴露于生物环境时，它们的表面被蛋白质和生物分子覆盖，称为蛋白质冠，降低了主动靶向能力。我们展示了一种化学策略来克服这个问题，通过阻断金纳米星上自组装单层的活性基团来减少蛋白质冠的厚度。根据碳链的电荷和长度，选择了最佳的封闭剂2-巯基乙醇。通过使用纳米抗体作为人表皮生长因子2受体（HER 2）的生物配体，通过使用暗场显微镜和光声成像在实验肿瘤模型中在体外和体内证明了主动靶向。在这项研究中，我们已经建立了金纳米星作为一个可以想象的治疗诊断剂与HER 2阳性肿瘤的特异性。(C)2017爱思唯尔有限公司版权所有。
Gold nanoparticles hold great promise as anti-cancer theranostic agents against cancer by actively targeting the tumor cells. As this potential has been supported numerously during in vitro experiments, the effective application is hampered by our limited understanding and control of the interactions within complex in vivo biological systems. When these nanoparticles are exposed to a biological environment, their surfaces become covered with proteins and biomolecules, referred to as the protein corona, reducing the active targeting capabilities. We demonstrate a chemical strategy to overcome this issue by reducing the protein corona's thickness by blocking the active groups of the self-assembled monolayer on gold nanostars. An optimal blocking agent, 2-mercapto ethanol, has been selected based on charge and length of the carbon chain. By using a nanobody as a biological ligand of the human epidermal growth factor 2 receptor (HER2), the active targeting is demonstrated in vitro and in vivo in an experimental tumor model by using darkfield microscopy and photoacoustic imaging. In this study, we have established gold nanostars as a conceivable theranostic agent with a specificity for HER2-positive tumors. (C) 2017 Elsevier Ltd. All rights reserved.