Dual-Functionalized Janus Mesoporous Silica Nanoparticles with Active Targeting and Charge Reversal for Synergistic Tumor-Targeting Therapy
Dual-Functionalized Janus Mesoporous Silica Nanoparticles with Active Targeting and Charge Reversal for Synergistic Tumor-Targeting Therapy
复制标题
具有主动靶向和电荷反转功能的双功能化 Janus 介孔二氧化硅纳米粒子，用于协同肿瘤靶向治疗
DOI：
10.1021/acsami.9b15434
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发表时间：
2019-11-27
影响因子：
9.5
通讯作者：
Ma, Kun
中科院分区：
文献类型：
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作者：
Liu, Yajun;Dai, Rui;Ma, Kun
具有各向异性特征的双面神纳米粒子将多种特性集中在单一载体上，产生协同效应。在本研究中，构建了双功能化的双面神纳米粒子（HA - JMSN / DOX - DMMA），其一侧修饰有肿瘤靶向配体（透明质酸，HA），另一侧有电荷反转基团（2,3 - 二甲基马来酸酐，DMMA）。HA - JMSN / DOX - DMMA的药物释放与环境酸度呈正相关。HA - JMSN / DOX - DMMA的细胞毒性和细胞摄取能力优于各向同性纳米粒子。HA - JMSN / DOX - DMMA的内吞途径同时涉及网格蛋白介导的内吞作用（HA）和微胞饮作用（DMMA），这表明它们都参与了纳米粒子与肿瘤细胞之间的相互作用。在小鼠静脉注射后，HA - JMSN / DOX - DMMA在肿瘤中的分布显著增强。体内抗肿瘤治疗研究表明，HA - JMSN / DOX - DMMA能有效抑制肿瘤生长，提高荷瘤小鼠的存活率。总体而言，HA - JMSN / DOX - DMMA能够发挥主动靶向和电荷反转的协同作用，在肿瘤细胞中递送药物并高效杀伤肿瘤细胞，是一种有前景的抗肿瘤纳米药物。
Janus nanoparticles with an anisotropic feature concentrated multiple properties on a single carrier, providing synergistic effects. In this study, dual-functionalized Janus nanoparticles (HA-JMSN/DOX-DMMA) were constructed with a tumor-targeting ligand (hyaluronic acid, HA) modified on the one side and a charge reversal group (2,3-dimethylmaleic anhydride, DMMA) on the other side. The drug release of HA-JMSN/DOX-DMMA was positively correlated with the acidity of the environment. The cytotoxicity and cell uptake of HA-JMSN/DOX-DMMA were superior to the isotropous nanoparticles. The endocytosis pathway of HA-JMSN/DOX-DMMA involved the clathrin-mediated endocytosis (HA) and the micropinocytosis (DMMA) at the same time, which indicated that they both participated in the interaction between nanoparticles and tumor cells. After being injected intravenously in mice, the distribution of HA-JMSN/DOX-DMMA in tumor was enhanced significantly. The antitumor therapy study in vivo showed that HA-JMSN/DOX-DMMA inhibited tumor growth and improved the survival rate of tumor-bearing mice effectively. In general, HA-JMSN/DOX-DMMA could take the synergistic effect of active targeting and charge reversal to deliver drug in tumor cells and kill them efficiently, which was a promising antitumor nanodrug.