Department of Biology, Faculty of Science, Ferdowsi University of Mashhad, Mashhad, Iran.
Department of Medicinal Chemistry, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
Carbohydr Polym. 2021 Aug 15;266:118111. doi: 10.1016/j.carbpol.2021.118111. Epub 2021 Apr 24.
Herein, a novel targeted delivery system was developed for intracellular co-delivery of doxorubicin (DOX) as a chemotherapeutic drug, antimiR-21 as an oncogenic antagomiR. In this system, DOX was loaded into mesoporous silica nanoparticles (MSNs) and chitosan was applied to cover the surface of MSNs. AS1411 aptamer as targeting nucleolin and antimiR-21 were electrostatically attached onto the surface of the chitosan-coated MSNs and formed the final nanocomplex (AACS nanocomplex). The study of drug release was based on DOX release under pH 7.4 and 5.5. Cellular toxicity and cellular uptake assessments of AACS nanocomplex were carried out in nucleolin positive (C26, MCF-7, and 4T1) and nucleolin negative (CHO) cell lines using MTT assay and flow cytometry analysis, respectively. Also, Anti-tumor efficacy of AACS nanocomplex was evaluated in C26 tumor-bearing mice. Overall, the results show that the combination therapy of DOX and antimiR-21, using AACS nanocomplex, could combat the cancer cell growth rate.
在此，开发了一种新型靶向递药系统，用于细胞内共递送阿霉素（DOX）作为化疗药物和抗 miR-21 作为致癌反义 miR。在该系统中，DOX 被装载到介孔硅纳米粒子（MSNs）中，并应用壳聚糖覆盖 MSNs 的表面。AS1411 适体作为靶向核仁素，与抗 miR-21 静电附着在壳聚糖包覆的 MSNs 表面上，形成最终的纳米复合物（AACS 纳米复合物）。药物释放研究基于 DOX 在 pH 7.4 和 5.5 下的释放。使用 MTT 测定法和流式细胞术分析，分别在核仁素阳性（C26、MCF-7 和 4T1）和核仁素阴性（CHO）细胞系中进行 AACS 纳米复合物的细胞毒性和细胞摄取评估。此外，还在 C26 荷瘤小鼠中评估了 AACS 纳米复合物的抗肿瘤功效。总的来说，结果表明，使用 AACS 纳米复合物的 DOX 和抗 miR-21 的联合治疗可以抑制癌细胞的生长速度。
