Mao Wei, Lee Sol, Shin Ji Un, Yoo Hyuk Sang
Department of Biomedical Materials Engineering, Kangwon National University, Chuncheon 24341, Korea.
Institute for Molecular Science and Fusion Technology, Kangwon National University, Chuncheon 24341, Korea.
Pharmaceutics. 2020 Mar 13;12(3):261. doi: 10.3390/pharmaceutics12030261.
Surface initiated atom transfer radical polymerization (SI-ATRP) documented a simple but efficient technique to grow a dense polymer layer on any surface. Gold nanoparticles (AuNPs) give a broad surface to immobilize sulfhyryl group-containing initiators for SI-ATRP; in addition, AuNPs are the major nanoparticulate carriers for delivery of anti-cancer therapeutics, since they are biocompatible and bioinert. In this work, AuNPs with a disulfide initiator were polymerized with sulfoethyl methacrylate by SI-ATRP to decorate the particles with anionic corona, and branched polyethyeleneimine (PEI) and siRNA were sequentially layered onto the anionic corona of AuNP by electrostatic interaction. The in vitro anti-cancer effect confirmed that AuNP with anionic corona showed higher degrees of apoptosis as well as suppression of the oncogene expression in a siRNA dose-dependent manner. The in vivo study of tumor-bearing nude mice revealed that mice treated with c-Myc siRNA-incorporated AuNPs showed dramatically decreased tumor size in comparison to those with free siRNA for 4 weeks. Furthermore, histological examination and gene expression study revealed that the decorated AuNP significantly suppressed c-Myc expression. Thus, we envision that the layer-by-layer assembly on the anionic brushes can be potentially used to incorporate nucleic acids onto metallic particles with high transfection efficiency.
表面引发原子转移自由基聚合反应(SI-ATRP)是一种在任何表面生长致密聚合物层的简单而有效的技术。金纳米颗粒(AuNPs)为SI-ATRP提供了广阔的表面来固定含巯基的引发剂;此外,AuNPs是抗癌治疗药物递送的主要纳米颗粒载体,因为它们具有生物相容性和生物惰性。在这项工作中,通过SI-ATRP使带有二硫键引发剂的AuNPs与甲基丙烯酸磺乙酯聚合,用阴离子冠层修饰颗粒,然后通过静电相互作用将支化聚乙烯亚胺(PEI)和小干扰RNA(siRNA)依次层叠在AuNP的阴离子冠层上。体外抗癌效果证实,带有阴离子冠层的AuNP表现出更高程度的细胞凋亡以及以siRNA剂量依赖性方式抑制癌基因表达。对荷瘤裸鼠的体内研究表明,与用游离siRNA处理的小鼠相比,用掺入c-Myc siRNA的AuNPs处理的小鼠在4周内肿瘤大小显著减小。此外,组织学检查和基因表达研究表明,修饰后的AuNP显著抑制了c-Myc的表达。因此,我们设想在阴离子刷上进行逐层组装有可能用于将核酸以高转染效率掺入金属颗粒中。