iRGD-Mediated and Enzyme-Induced Precise Targeting and Retention of Gold Nanoparticles for the Enhanced Imaging and Treatment of Breast Cancer
iRGD-Mediated and Enzyme-Induced Precise Targeting and Retention of Gold Nanoparticles for the Enhanced Imaging and Treatment of Breast Cancer
复制标题
iRGD 介导和酶诱导的金纳米颗粒精确靶向和保留，用于增强乳腺癌的成像和治疗
DOI：
10.1166/jbn.2018.2592
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发表时间：
2018
影响因子：
2.9
通讯作者：
Yu Zhiqiang
中科院分区：
文献类型：
--
作者：
Yang Yuanyuan;Chen Qiling;Li Siyu;Ma Wen;Yao Guangyu;Ren Fei;Cai Zheng;Zhao Peng;Liao Guochao;Xiong Jingyuan;Yu Zhiqiang
尽管纳米药物在癌症化疗中取得了巨大的成就，但精确的肿瘤靶向和深度渗透仍然是主要的挑战。许多纳米药物只能通过增强透留效应（EPR）在肿瘤血管渗漏部位附近被动积累，无法到达肿瘤深部。为了提高肿瘤靶向、穿透和保留效率，通过将肿瘤归巢渗透肽iRGD （CRGDKGPDC）与豆科蛋白反应性可聚集金纳米颗粒（AuNPs-A&C）共同作用，建立了iRGD介导和酶诱导的精确靶向金纳米颗粒系统（iRGD/AuNPs-A&C）。在体外实验中，iRGD/AuNPs-A&C的大小与AuNPs-A&C的大小增加速率一致，表明iRGD/AuNPs-A&C在豆科蛋白存在的情况下也可以聚集，有利于其在肿瘤微环境中的保留增强。与此同时，iRGD/AuNPs-A&C在体外比AuNPs-A&C对4T1细胞有更高的细胞摄取，在体内比AuNPs-A&C在乳腺肿瘤中有更高的渗透和积聚，从而提高了肿瘤成像效能，改善了对4T1荷瘤小鼠的化疗效果。这些结果表明，irgd介导和酶诱导的双功能纳米平台在4T1肿瘤成像和治疗中具有广阔的应用前景。
Despite the great achievements of nanomedicines made in cancer chemotherapy, precise tumor targeting and deep penetration are still major challenges. Many nanomedicines can only passively accumulate near leaky site of tumor vessels through the enhanced permeability and retention (EPR) effect and cannot reach the deep region of tumor. To improve the tumor targeting, penetration and retention efficiency, an iRGD-mediated and enzyme-induced precise targeting gold nanoparticles system (iRGD/AuNPs-A&C) was developed by simply coadministering a tumor-homing penetration peptide iRGD (CRGDKGPDC) with a legumain responsive aggregable gold nanoparticle (AuNPs-A&C). In vitro, iRGD/AuNPs-A&C showed a consistent increase rate in size with AuNPs-A&C, suggesting that iRGD/AuNPs-A&C could also aggregate in the presence of legumain, which was in favor of the enhanced retention in tumor microenvironment. Meanwhile, iRGD/AuNPs-A&C showed higher 4T1 cells cellular uptake in vitro and presented higher penetration and accumulation in breast tumor in vivo than AuNPs-A&C, leading to enhanced tumor imaging efficacy and the improved chemotherapeutic effect to 4T1-bearing mice. These results suggested that the iRGD-mediated and enzyme-induced dual-functional nanoplatform was promising for the 4T1 tumor imaging and treatment.