Department of Molecular Science and Technology, Ajou University, Suwon 443-749, Republic of Korea.
Biomedical Engineering, Yale University, CT 06511, USA.
Colloids Surf B Biointerfaces. 2017 Aug 1;156:71-78. doi: 10.1016/j.colsurfb.2017.05.007. Epub 2017 May 3.
We describe a facile and effective poly(ethylene glycol) (PEG) coating method that has not been used previously for decoration of nanogels. Layer-by-layer (LbL) assembly was the technique of choice to introduce PEG onto the surface of multi-layered nanogels (MLNGs). Pegylated MLNGs were prepared simply by sequentially dispersing nanogels in solutions of cationic polymer, anionic polymer, and modified PEGs, and each coating step was validated by measuring changes in size and surface charge. Particularly, a peptide linker that is cleavable by matrix metalloproteinase-2 (MMP-2) in the tumor microenvironment was introduced between PEG layer and nanogels because it is known that PEG reduces the uptake of nanoparticles in tumor cells due to its high mobility. In vitro cell studies demonstrated that MLNGs with MMP-cleavable PEGs enhanced the particle uptake up to 3 times in tumor cells due to unmasking of PEG brushes as compared to pegylated MLNGs without MMP-sensitive peptide linkers.
我们描述了一种以前未曾用于纳米凝胶修饰的简便有效的聚乙二醇（PEG）涂层方法。层层（LbL）组装是将 PEG 引入多层纳米凝胶（MLNG）表面的首选技术。通过将纳米凝胶依次分散在阳离子聚合物、阴离子聚合物和修饰的 PEG 的溶液中，即可简单地制备 PEG 化的 MLNG，并且通过测量粒径和表面电荷的变化来验证每个涂层步骤。特别地，在 PEG 层和纳米凝胶之间引入了一种可被肿瘤微环境中的基质金属蛋白酶-2（MMP-2）切割的肽接头，因为已知由于其高迁移率，PEG 会降低纳米颗粒在肿瘤细胞中的摄取。体外细胞研究表明，与没有 MMP 敏感肽接头的 PEG 化 MLNG 相比，具有 MMP 可切割 PEG 的 MLNG 由于 PEG 刷的暴露，可将颗粒摄取提高至肿瘤细胞中的 3 倍。
