Crosstalk between Hepatic Glutathione Efflux and Tumor Targeting Efficiency of Indocyanine Green‐Conjugated Gold Nanoparticles
Crosstalk between Hepatic Glutathione Efflux and Tumor Targeting Efficiency of Indocyanine Green‐Conjugated Gold Nanoparticles
复制标题
肝脏谷胱甘肽流出与吲哚菁绿-共轭金纳米粒子的肿瘤靶向效率之间的串扰
DOI：
10.1002/anie.202308909
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Zheng, Jie
中科院分区：
文献类型：
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作者：
Huang, Yingyu;Xiao, Wei;Ahrari, Samira;Yu, Mengxiao;Zheng, Jie
实体瘤中谷胱甘肽（GSH）水平升高已被用作GSH响应性纳米颗粒的主要标志，以提高靶向效率和特异性。同时，GSH主要在体内肝脏的肝细胞内合成，并通过肝脏GSH流出不断释放到血液中，以调节整个身体的氧化还原电位。然而，这种肝脏GSH流出如何影响GSH响应性纳米颗粒的肿瘤靶向仍然是未知的。在本文中，我们报告了肝脏GSH的耗尽增强了GSH响应性吲哚菁绿色-缀合的Au 25纳米团簇（ICG-Au 25 SG 18）的肿瘤靶向，所述Au 25纳米团簇涂覆有18 GSH配体。通过巯基交换反应，ICG通过肝脏GSH从Au 25 SG 18上解离，随后通过GSH耗尽减缓了解离的ICG的肝胆清除，这反过来延长了完整ICG-Au 25 SG 18的血液循环，并增强了其肿瘤靶向性。我们的工作强调了谷胱甘肽介导的肝脏和肿瘤之间的串扰，除了众所周知的枯否细胞介导的摄取，在工程纳米颗粒的肿瘤靶向中，可以调节以提高癌症纳米药物的靶向效率和特异性，同时减少其非特异性积累。
The elevated glutathione (GSH) level in solid tumors has been used as a major hallmark for GSH‐responsive nanoparticles to enhance targeting efficiency and specificity. Meanwhile, GSH is mainly synthesized inside the hepatocytes of the liver in the body and constantly released into the blood through hepatic GSH efflux to regulate redox potential of the entire body. However, it remains largely unknown how this hepatic GSH efflux affects the tumor targeting of GSH‐responsive nanoparticles. Herein, we report that depletion of hepatic GSH enhanced the tumor targeting of GSH‐responsive indocyanine green‐conjugated Au25nanoclusters coated with 18 GSH ligand (ICG‐Au25SG18). The dissociation of ICG from Au25SG18by the hepatic GSH through thiol‐exchange reaction and the subsequent hepatobiliary clearance of the detached ICG were slowed down by GSH depletion, which in turn prolonged the blood circulation of intact ICG‐Au25SG18and enhanced its tumor targeting. Our work highlights glutathione‐mediated crosstalk between the liver and tumor, in addition to well‐known Kupffer cell‐mediated uptake, in the tumor targeting of engineered nanoparticles, which could be modulated to enhance targeting efficiency and specificity of cancer nanomedicines while reducing their nonspecific accumulation.