研究动态
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Dendrimer-microRNA纳米制剂对胶质母细胞瘤干细胞的影响。

Effects of Dendrimer-microRNA Nanoformulations against Glioblastoma Stem Cells.

发表日期:2023 Mar 17
作者: Nadezhda Knauer, Mariya Meschaninova, Sajjad Muhammad, Daniel Hänggi, Jean-Pierre Majoral, Ulf Dietrich Kahlert, Vladimir Kozlov, Evgeny K Apartsin
来源: Stem Cell Research & Therapy

摘要:

胶质母细胞瘤是一种快速进展、难以治疗的肿瘤。这些特征目前被归属于一群自我维持的胶质母细胞。抗肿瘤干细胞治疗需要全新的治疗手段,具体而言,基于微小RNA的治疗是一种解决方案,这又需要特定的载体来传递功能性寡核苷酸。在本文中,我们报道了一种使用聚阳电性磷和碳硅烷树状分子体系中的抗肿瘤微小RNA miR-34a和微小RNA-21合成抑制剂的纳米制剂,在临床前体外验证了其抗肿瘤活性。测试在一系列胶质母细胞瘤和胶质瘤细胞株、胶质母细胞瘤干细胞和诱导多能干细胞中进行。我们表明,树状分子微小RNA纳米制剂能够以可控的方式诱导细胞死亡,在肿瘤细胞中的细胞毒性效果比非肿瘤干细胞更加显著。此外,纳米制剂对介导肿瘤和其免疫微环境相互作用的蛋白质表达(PD-L1、TIM3、CD47和IL-10)产生了影响。我们的研究结果表明,基于树状分子的治疗构造具有进一步研究的抗肿瘤干细胞治疗潜力。
Glioblastoma is a rapidly progressing tumor quite resistant to conventional treatment. These features are currently assigned to a self-sustaining population of glioblastoma stem cells. Anti-tumor stem cell therapy calls for a new means of treatment. In particular, microRNA-based treatment is a solution, which in turn requires specific carriers for intracellular delivery of functional oligonucleotides. Herein, we report a preclinical in vitro validation of antitumor activity of nanoformulations containing antitumor microRNA miR-34a and microRNA-21 synthetic inhibitor and polycationic phosphorus and carbosilane dendrimers. The testing was carried out in a panel of glioblastoma and glioma cell lines, glioblastoma stem-like cells and induced pluripotent stem cells. We have shown dendrimer-microRNA nanoformulations to induce cell death in a controllable manner, with cytotoxic effects being more pronounced in tumor cells than in non-tumor stem cells. Furthermore, nanoformulations affected the expression of proteins responsible for interactions between the tumor and its immune microenvironment: surface markers (PD-L1, TIM3, CD47) and IL-10. Our findings evidence the potential of dendrimer-based therapeutic constructions for the anti-tumor stem cell therapy worth further investigation.