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Unsymmetrical Low-Generation Cationic Phosphorus Dendrimers as a Nonviral Vector to Deliver MicroRNA for Breast Cancer Therapy
Biomacromolecules ( IF 5.5 ) Pub Date : 2024-01-05 , DOI: 10.1021/acs.biomac.3c01169
Yu Zou 1, 2 , Siyan Shen 3 , Andrii Karpus 1, 2 , Huxiao Sun 3 , Regis Laurent 1, 2 , Anne-Marie Caminade 1, 2 , Mingwu Shen 3 , Serge Mignani 4, 5 , Xiangyang Shi 3, 4 , Jean-Pierre Majoral 1, 2
Affiliation  

The development of nonviral dendritic polymers with a simple molecular backbone and great gene delivery efficiency to effectively tackle cancer remains a great challenge. Phosphorus dendrimers or dendrons are promising vectors due to their structural uniformity, rigid molecular backbones, and tunable surface functionalities. Here, we report the development of a new low-generation unsymmetrical cationic phosphorus dendrimer bearing 5 pyrrolidinium groups and one amino group as a nonviral gene delivery vector. The created AB5-type dendrimers with simple molecular backbone can compress microRNA-30d (miR-30d) to form polyplexes with desired hydrodynamic sizes and surface potentials and can effectively transfect miR-30d to cancer cells to suppress the glycolysis-associated SLC2A1 and HK1 expression, thus significantly inhibiting the migration and invasion of a murine breast cancer cell line in vitro and the corresponding subcutaneous tumor mouse model in vivo. Such unsymmetrical low-generation phosphorus dendrimers may be extended to deliver other genetic materials to tackle other diseases.

中文翻译:


不对称的低代阳离子磷树状聚体作为非病毒载体递送 microRNA 用于乳腺癌治疗



开发具有简单分子骨架和出色基因递送效率的非病毒树突状聚合物以有效应对癌症仍然是一项巨大的挑战。磷树状体或树突因其结构均匀性、刚性分子骨架和可调的表面官能团而成为有前途的载体。在这里,我们报道了一种新的低代不对称阳离子磷树枝大聚体的开发,该树枝状聚合物具有 5 个吡咯烷基团和一个氨基作为非病毒基因递送载体。所创建的具有简单分子骨架的 AB5 型树状聚体可以压缩 microRNA-30d (miR-30d) 形成具有所需流体动力学大小和表面电位的多链体,并且可以有效地将 miR-30d 转染到癌细胞中,以抑制糖酵解相关的 SLC2A1 和 HK1 表达,从而在体外显着抑制小鼠乳腺癌细胞系和相应的体内皮下肿瘤小鼠模型的迁移和侵袭.这种不对称的低代磷树状物可以扩展到输送其他遗传物质来应对其他疾病。
更新日期:2024-01-05
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