Increased Gold Nanoparticle Retention in Brain Tumors by in Situ Enzyme-Induced Aggregation
Increased Gold Nanoparticle Retention in Brain Tumors by in Situ Enzyme-Induced Aggregation
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通过原位酶诱导聚集增加金纳米粒子在脑肿瘤中的保留
DOI：
10.1021/acsnano.6b05070
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发表时间：
2016-11-01
期刊：
影响因子：
17.1
通讯作者：
Gao, Huile
中科院分区：
文献类型：
--
作者：
Ruan, Shaobo;Hu, Chuan;Gao, Huile
由于药物和纳米颗粒的积累有限，脑肿瘤的治疗仍然是一个挑战。在这里，我们使用豆蔻蛋白触发金纳米颗粒（AuNPs）的聚集，以增强化疗药物在脑肿瘤中的保留。该纳米平台AuNPs- a&c由Ala-Ala-Asn-Cys-Lys修饰的AuNPs （AuNPs- ak）和2-氰基-6-氨基-苯并噻唑修饰的AuNPs （AuNPs- cabt）组成。在豆科蛋白存在的情况下，AuNPs- ak可以水解，暴露出AuNPs- ak上的1,2-硫氨基，这是通过与AuNPs- cabt上相邻的氰基进行点击环加成而发生的，从而形成AuNPs聚集体。由于阻断纳米颗粒胞外分泌和减少纳米颗粒回流到血液，该策略导致体外和体内胶质瘤细胞中AuNPs的保留增强。阿霉素（DOX）通过ph敏感连接物与AuNPs-A&C偶联后，治疗胶质瘤的效率得到提高。与生理盐水组相比，dox相关的AuNPs-A&C的中位生存时间增加到288%。我们进一步展示了AuNPs-A&C在光学成像应用中的应用。总之，我们提供了一种增加纳米颗粒肿瘤积累的策略，有可能改善治疗结果。
The treatment of brain tumors remains a challenge due to the limited accumulation of drugs and nanoparticles. Here, we triggered the aggregation of gold nanoparticles (AuNPs) using legumain to enhance the retention of chemotherapeutics in brain tumors. This nanoplatform, AuNPs-A&C, is comprised of Ala-Ala-Asn-Cys-Lys modified AuNPs (AuNPs-AK) and 2-cyano-6-amino-benzothiazole modified AuNPs (AuNPs-CABT). AuNPs-AK could be hydrolyzed to expose the 1,2-thiolamino groups on AuNPs-AK in the presence of legumain, which occurs by a click cycloaddition with the contiguous cyano group on AuNPs-CABT, resulting in formation of AuNPs aggregates. This strategy led to an enhanced retention of the AuNPs in glioma cells both in vitro and in vivo due to the blocking of nanoparticle exocytosis and minimizing nanoparticle backflow to the bloodstream. After conjugation of doxorubicin (DOX) via a pH-sensitive linker to AuNPs-A&C, the efficiency for treating glioma was improved. The median survival time for the DOX-linked AuNPs-A&C increased to 288% in comparison to the saline group. We further show the use of the AuNPs-A&C for optical imaging applications. In conclusion, we provide a strategy to increase nanoparticle tumor accumulation with the potential to improve therapeutic outcome.