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磁性核壳 S-亚硝酰化硫醇纳米粒子作为肿瘤双重靶向治疗平台。

Magnetic core-shell S-nitrosothiols nanoparticles as tumor dual-targeting theranostic platform.

机构信息

College of Chemistry, Chemical Engineering and Materials Science, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Shandong Normal University, Jinan 250014, PR China.

College of Chemistry, Chemical Engineering and Materials Science, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Shandong Normal University, Jinan 250014, PR China.

出版信息

Colloids Surf B Biointerfaces. 2019 Sep 1;181:400-407. doi: 10.1016/j.colsurfb.2019.05.075. Epub 2019 May 30.

Abstract

The external force guided targeting strategy, as well as the in vivo active targeting strategy based on "ligands-receptors" on the targeting cells and tissues have attracted much research interest. Herein, a kind of hyaluronic acid (HA) and folic acid (FA) modified magnetic S-nitrosothiols core-shell nanoparticles for nitric oxide (NO) control release as dual-tumor targeting theranostic platform were described, combining the external guidance and internal active targeting properties. Confocal microscopy assay and cells cytotoxicity experiments confirmed the active tumor cells targeting recognition, cells uptake, and NO initiated cytotoxicity of the HA-FA external functional layer modified S-nitrosothiols nanoparticles in vitro. In vivo magnetic resonance imaging (MRI) characterization, bio-distribution assay in organs and tumor, significant tumor inhibition efficacy, survival units of the mice bearing tumor, as well as the systemic toxicity assay demonstrated the efficiency of cooperative tumor targeting diagnosis and controlled NO-releasing chemotherapy. To the best of our knowledge, this is the first time of the external magnet and HA-FA actively induced synergistic effect tumor targeting systems based on NO chemotherapy in vivo, serving as a new theranostic system.

摘要

外力引导靶向策略,以及基于靶向细胞和组织上“配体-受体”的体内主动靶向策略,引起了广泛的研究兴趣。在此,我们描述了一种基于磁硫醇的靶向治疗平台,该平台由透明质酸(HA)和叶酸(FA)修饰的磁性 S-亚硝基硫醇核壳纳米粒子组成,用于一氧化氮(NO)的控制释放,结合了外部引导和内部主动靶向特性。共聚焦显微镜检测和细胞毒性实验证实了 HA-FA 外部功能层修饰的 S-亚硝基硫醇纳米粒子在体外具有主动的肿瘤细胞靶向识别、细胞摄取和 NO 引发的细胞毒性作用。体内磁共振成像(MRI)特征、器官和肿瘤中的生物分布试验、显著的肿瘤抑制效果、荷瘤小鼠的生存单位,以及系统毒性试验证明了协同肿瘤靶向诊断和控制 NO 释放化疗的效率。据我们所知,这是首次在体内基于 NO 化疗的外部磁场和 HA-FA 主动诱导协同作用的肿瘤靶向系统,作为一种新的治疗系统。

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