Toxicology and Diseases Group, The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences (TUMS), Tehran, Iran.
Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
Int J Pharm. 2019 Apr 5;560:306-314. doi: 10.1016/j.ijpharm.2019.02.016. Epub 2019 Feb 20.
The present study aimed to investigate in vitro DNA transfection efficiency of three novel chitosan derivatives: thiolated trimethyl chitosan (TMC-Cys), methylated 4-N,N dimethyl aminobenzyl N,O carboxymethyl chitosan(MABCC) and thiolated trimethyl aminobenzyl chitosan(MABC-Cys). After polymer synthesis and characterization, nanoparticles were prepared using these polymers and their size, zeta potential and DNA condensing ability were measured. After that, cytotoxicity and transfection efficiency of nanocomplexes were carried out in three different cells. The results showed that all polymers could condense DNA plasmid strongly from N/P 2 and nanocomplexes had eligible sizes and zeta potentials. Moreover, the nanocomplexes had negligible cytotoxicity and MABC-Cys was the most effective vehicle for gene delivery in HEK-293T cells. In the two other cell lines, SKOV-3 and MCF-7, TMC-Cys exhibited the highest transfection efficiency. This study indicated that chemical structure of these novel chitosan derivatives in the interaction with the cell type can lead to successful gene delivery.
巯基化三甲基壳聚糖（TMC-Cys）、甲基化 4-N,N-二甲氨基苄基 N,O-羧甲基壳聚糖（MABCC）和巯基化三甲基氨基苄基壳聚糖（MABC-Cys）的体外 DNA 转染效率。在聚合物合成和表征后，使用这些聚合物制备纳米粒，并测量其粒径、Zeta 电位和 DNA 凝聚能力。然后，在三种不同的细胞中进行纳米复合物的细胞毒性和转染效率实验。结果表明，所有聚合物都能从 N/P 2 强烈地凝聚 DNA 质粒，并且纳米复合物具有合适的粒径和 Zeta 电位。此外，纳米复合物的细胞毒性可以忽略不计，MABC-Cys 是 HEK-293T 细胞中最有效的基因传递载体。在另外两种细胞系 SKOV-3 和 MCF-7 中，TMC-Cys 表现出最高的转染效率。本研究表明，这些新型壳聚糖衍生物的化学结构与细胞类型的相互作用可以导致成功的基因传递。
