Dual ATP/reduction-responsive polyplex to achieve the co-delivery of doxorubicin and miR-23b for the cancer treatment
Dual ATP/reduction-responsive polyplex to achieve the co-delivery of doxorubicin and miR-23b for the cancer treatment
复制标题
双 ATP/还原响应复合物实现多柔比星和 miR-23b 的共同递送用于癌症治疗
DOI：
10.1016/j.colsurfb.2021.111955
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发表时间：
2021-06-30
影响因子：
5.8
通讯作者：
Li, Quanshun
中科院分区：
文献类型：
--
作者：
Tang, Xiuhui;Liang, Xiao;Li, Quanshun
基于治疗基因和抗癌药物共递送的联合治疗已成为肿瘤治疗的一种有前途的方法，而刺激响应性递送系统可以进一步提高治疗效果。本文中，使用ATP适体及其互补DNA形成Duplex，其中负载多柔比星（DOX）以构建DOX-Duplex，然后使用硫辛酸修饰的寡乙烯亚胺（LA-OEI）作为载体以实现DOX-Duplex和miR-23 b的共递送。LA-OEI/miR-23 b/DOX-Duplex三元纳米复合物通过线粒体信号通路诱导细胞凋亡，使细胞周期阻滞于S期，显示出良好的抗增殖作用。同时，DOXDuplex和miR-23 b的联合转染可以通过降低MMP-9的表达水平有效抑制癌细胞的转移。三元纳米复合物的良好抗肿瘤功效归因于响应于细胞内ATP浓度和还原条件的快速药物释放以及DOXDuplex与miR-23 b之间的协同效应。因此，ATP适体和还原响应性聚合物为构建双重刺激响应系统提供了一个方便的平台，用于癌症治疗中基因和药物的共递送。
Combination therapy based on the co-delivery of therapeutic genes and anti-cancer drugs has emerged as a promising approach in the cancer treatment, and stimuli-responsive delivery systems could further improve the therapeutic efficacy. Herein, an ATP aptamer and its complementary DNA were used to form Duplex into which doxorubicin (DOX) was loaded to construct DOX-Duplex, and then the lipoic acid-modified oligoethyleneimine (LA-OEI) was employed as a carrier to realize the co-delivery of DOX-Duplex and miR-23b. The ternary nano complex LA-OEI/miR-23b/DOX-Duplex showed excellent anti-proliferative effect by inducing the cell apoptosis via mitochondrial signaling pathway and arresting the cell cycle at S phase. Meanwhile, the co-delivery of DOXDuplex and miR-23b could efficiently inhibit the metastasis of cancer cells by reducing the expression level of MMP-9. The favorable anti-tumor efficacy of ternary nanocomplex was attributed to the rapid drug release in response to intracellular ATP concentration and reduction conditions and the synergistic effect between DOXDuplex and miR-23b. Thus, ATP aptamer and reduction-responsive polymer provided a convenient platform to construct dual stimuli-responsive systems for the co-delivery of gene and drug in the cancer treatment.