Antigen‐Free Radionuclide‐Embedded Gold Nanoparticles for Dendritic Cell Maturation, Tracking, and Strong Antitumor Immunity
Antigen‐Free Radionuclide‐Embedded Gold Nanoparticles for Dendritic Cell Maturation, Tracking, and Strong Antitumor Immunity
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DOI：
10.1002/adhm.201701369
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发表时间：
2018-05
影响因子：
10
通讯作者：
Sang Bong Lee;Young Ju Lee;S. Cho;Sang Kyoon Kim;Sang-Woo Lee;Jaetae Lee;Dong-Kwon Lim;Y. Jeon-Y.
中科院分区：
文献类型：
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作者：
Sang Bong Lee;Young Ju Lee;S. Cho;Sang Kyoon Kim;Sang-Woo Lee;Jaetae Lee;Dong-Kwon Lim;Y. Jeon-Y.
以树突状细胞(DC)为基础的肿瘤免疫治疗需要DC的高效成熟和对激活T细胞的淋巴结内DC的灵敏监测。本文报道了一种强健而简单的表面化学方法，用低聚酪氨酸修饰的金纳米粒子(Poly-Y-RIE-AuNPs)制备了高灵敏和稳定的放射性核素包埋金纳米粒子(Poly-Y-RIE-AuNPs)，作为一种有前途的正电子发射断层扫描/计算机断层扫描成像剂。修饰在AuNPs上的多个寡聚酪氨酸结合部位通过形成Au壳层为共轭放射性同位素提供了良好的稳定性。它们可以与放射性同位素碘大量结合，从而能够灵敏地追踪淋巴系统中的DC。更重要的是，我们发现单独使用Poly-Y-RIE-AuNPs可以在没有任何额外刺激的情况下实现DC的成熟。Poly-Y-RIE-AuNPs成熟的DC可诱导抗宫颈癌免疫，与肿瘤裂解物搏动DC产生的抗肿瘤免疫作用相当。这些结果表明，基于多肽的表面化学Poly-Y-RIE-AuNPs是一种简单、直接的方法来制备高灵敏和稳定的核医学显像剂，并提高了当前抗肿瘤免疫治疗的效率。
Dendritic cell (DC)‐based cancer immunotherapy requires efficient maturation of DCs and sensitive monitoring of DCs localized in the lymph nodes that activate T cells. This paper reports a robust and simple surface chemistry for highly sensitive and stable radionuclide‐embedded gold nanoparticles (Poly‐Y‐RIe‐AuNPs) prepared with oligotyrosine‐modified AuNPs with additional Au shell formation as a promising positron emission tomography/computed tomography imaging agent. The multiple oligotyrosine binding sites modified on AuNPs provide excellent stability for conjugated radioisotopes by forming an Au shell. They can be heavily conjugated with radioisotope iodine, which enables sensitive tracking of DCs in the lymphatic system. More importantly, it is found that the maturation of DCs is possible solely with Poly‐Y‐RIe‐AuNPs without any additional stimulus for DC maturation. DCs matured by Poly‐Y‐RIe‐AuNPs induce antitumor immunity to cervical cancer comparable to that produced from DCs pulsated with tumor lysates. These results demonstrate that the peptide‐based surface chemistry of Poly‐Y‐RIe‐AuNPs is a simple and straightforward method to produce a highly sensitive and stable nuclear medicine imaging agent that also improves the efficiency of current antitumor immunotherapies.