Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences , Changchun 130022, P. R. China.
University of Chinese Academy of Sciences , Beijing 100049, P. R. China.
Biomacromolecules. 2017 Apr 10;18(4):1342-1349. doi: 10.1021/acs.biomac.7b00080. Epub 2017 Mar 20.
In this study, a pH-responsive detachable polyethylene glycol (PEG) shielding strategy was designed for gene delivery in cancer therapy. Polyethylenimine/DNA complex (PEI/DNA) was in situ shielded by aldehyde group-modified PEG derivatives. The aldehyde groups of PEG could react with the amino groups of PEI by Schiff base reaction. The Schiff base bond was stable in neutral pH but labile in slightly acidic pH, which made the PEG sheddable in tumors. PEG-coated nanoparticles (NPs) had distinct advantages compared to their mPEG counterpart, possessing decreased zeta potential, more compressed size, and enhanced stability. PEG/PEI/DNA NPs showed not only high tumor cell uptake and transfection efficiency in vitro but also efficient accumulation and gene expression in solid tumors in vivo. This pH-responsive detachable PEG shielding system has the potential to be applied to other polycationic nanoparticles that contain amino groups on their surfaces, which will have broad prospects in cancer therapy.
在这项研究中，设计了一种 pH 响应性可分离聚乙二醇（PEG）屏蔽策略，用于癌症治疗中的基因传递。通过醛基修饰的 PEG 衍生物对聚乙烯亚胺/DNA 复合物（PEI/DNA）进行原位屏蔽。PEG 的醛基可以通过席夫碱反应与 PEI 的氨基反应。席夫碱键在中性 pH 下稳定，但在略酸性 pH 下不稳定，这使得 PEG 可以在肿瘤中脱落。与 mPEG 相比，PEG 包覆的纳米颗粒（NPs）具有明显的优势，其具有较低的 zeta 电位、更压缩的尺寸和增强的稳定性。PEG/PEI/DNA NPs 不仅在体外具有高的肿瘤细胞摄取和转染效率，而且在体内实体瘤中也具有高效的积累和基因表达。这种 pH 响应性可分离 PEG 屏蔽系统有可能应用于其他表面含有氨基的阳离子纳米颗粒，在癌症治疗中具有广阔的前景。
