MiRNA Delivery System Based on Stimuli-Responsive Gold Nanoparticle Aggregates for Multimodal Tumor Therapy
MiRNA Delivery System Based on Stimuli-Responsive Gold Nanoparticle Aggregates for Multimodal Tumor Therapy
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基于刺激响应金纳米颗粒聚集体的 miRNA 递送系统，用于多模式肿瘤治疗
DOI：
10.1021/acsabm.9b00240
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发表时间：
2019
期刊：
影响因子：
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通讯作者：
Xin Chen
中科院分区：
文献类型：
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作者：
Xiangdong Wang;Nuo Jin;Qiao Wang;Tao Liu;Kangcan Liu;Yan Li;Yongkang Bai;Xin Chen
在这项工作中，制备了 microRNA-124-5p 模拟物 (miR-124-5p) 和金纳米颗粒 (AuNP) 聚集体的复合材料，将基因疗法和光热疗法结合起来，实现有效的肿瘤医学。由胱胺交联的 AuNP 聚集体不仅可以用作光热治疗剂，而且由于库仑相互作用，能够将 miR-124-5p 凝聚为用于基因递送的纳米载体。当纳米载体通过内吞作用进入含有高浓度谷胱甘肽（GSH）的肿瘤细胞的细胞质时，胱胺的裂解可以启动miR-124-5p的释放。此外，在GSH触发的miR-124-5p释放后，由于二硫键的同时破坏和硫醇-金键的重组，AuNP聚集体的大小没有变化，从而导致纳米载体用于肿瘤治疗的持续光热特性。体外实验表明，近红外辐射下的miRNA@AuNAs（miR-124-5p）复合物对肿瘤细胞表现出极大的细胞毒性，分别比近红外辐射下的纯AuNP聚集体和未经近红外辐射的miRNA@AuNAs复合物组高2倍和3倍。所有实验统计表明，光热疗法和基因疗法相结合的miRNA@AuNAs复合物在有效治疗肿瘤方面具有巨大的潜力。
In this work, a composite of microRNA-124-5p mimics (miR-124-5p) and gold nanoparticle (AuNP) aggregates was fabricated to combine the gene therapy and photothermal therapy for effective tumor medicine. The AuNP aggregates cross-linked by cystamine not only serve as photothermal therapeutic agents but are able to condense miR-124-5p as nanocarrier for gene delivery because of the coulomb interaction. The release of miR-124-5p could be initiated by the cleavage of cystamine when the nanocarrier enter the cytoplasm of tumor cells through endocytosis, where contains high concentration of glutathione (GSH). Moreover, the size of the AuNP aggregates did not change after the GSH-triggered miR-124-5p release because of the coinstantaneous disruption of disulfide bond and reformation of the thiol–gold bond, resulting in sustained photothermal property of the nanocarrier for tumor therapy. In vitro experiments showed that the miRNA@AuNAs (miR-124-5p) composite under near-infrared radiation performed great cytotoxicity to tumor cells, which is two and three times higher than the group of pure AuNP aggregates under near-infrared radiation and miRNA@AuNAs composite without near-infrared radiation, respectively. All experiment statistics show that the miRNA@AuNAs composite with combination of photothermal therapy and gene therapy has great potential for effective tumor treatment.