Nia Azadeh Hashem, Eshghi Hossein, Abnous Kalil, Ramezani Mohammad
Pharmaceutical Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Chemistry, School of Sciences, Ferdowsi University of Mashhad, Mashhad, Iran.
Department of Chemistry, School of Sciences, Ferdowsi University of Mashhad, Mashhad, Iran.
Eur J Pharm Sci. 2017 Mar 30;100:176-186. doi: 10.1016/j.ejps.2017.01.014. Epub 2017 Jan 16.
A series of polyethylenimine conjugates of single-walled carbon nanotube (PEI-SWNT) containing bioreducible disulfide bonds was synthesized and evaluated for their transfection efficiency. Different molecular weights of polyethylenimine (PEI) were thiolated with different mole ratio of 2-iminothiolane (2-IT). Single-walled carbon nanotube (SWNT) was first carboxylated and then three different cysteine-functionalized SWNT formulations were synthesized via introduced linkers: a) carbonyl group b) spermidine c) 1,8-diamino 3,6-dioxo octane. The final nanocarriers were fabricated upon conjugation of thiolated PEIs and thiolated SWNT via oxidative disulfide bond formation. All PEI-disulfide-SWNT conjugates were capable of DNA condensation and showed improved viability and transfection efficiency compared to PEI itself. Transfection efficiencies were up to 1500 times greater than PEI 25kDa (C/P=0.8). The results of this study suggest that the synthesized formulations based on SWNT-CO-Cysteine and PEI 1.8kDa were the most efficient carriers. Considering the decreased cytotoxicity and higher transfection levels, the conjugates bear the potential for effective delivery of genetic materials.
合成了一系列含有可生物还原二硫键的单壁碳纳米管聚乙烯亚胺共轭物（PEI-SWNT），并对其转染效率进行了评估。用不同摩尔比的2-亚氨基硫醇（2-IT）对不同分子量的聚乙烯亚胺（PEI）进行硫醇化。首先将单壁碳纳米管（SWNT）羧化，然后通过引入连接体合成三种不同的半胱氨酸功能化SWNT制剂：a）羰基b）亚精胺c）1,8-二氨基3,6-二氧代辛烷。通过氧化二硫键形成，将硫醇化的PEI与硫醇化的SWNT共轭，制备出最终的纳米载体。所有PEI-二硫键-SWNT共轭物都能够凝聚DNA，并且与PEI本身相比，显示出更高的活力和转染效率。转染效率比PEI 25kDa（C/P=0.8）高1500倍。本研究结果表明，基于SWNT-CO-半胱氨酸和PEI 1.8kDa合成的制剂是最有效的载体。考虑到细胞毒性降低和转染水平提高，这些共轭物具有有效递送遗传物质的潜力。
