School of Chemistry and Chemical Engineering, State Key Laboratory of Metal Matrix Composites, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai, 200240, China.
Department of Electronic Engineering (Biomedical Engineering), The Chinese University of Hong Kong, China, Shatin, New Territories, Hong Kong, China.
Angew Chem Int Ed Engl. 2018 Mar 12;57(12):3064-3068. doi: 10.1002/anie.201711242. Epub 2018 Feb 22.
Functional siRNAs are employed as cross-linkers to direct the self-assembly of DNA-grafted polycaprolactone (DNA-g-PCL) brushes to form spherical and nanosized hydrogels via nucleic acid hybridization in which small interfering RNAs (siRNAs) are fully embedded and protected for systemic delivery. Owing to the existence of multivalent mutual crosslinking events inside, the crosslinked nanogels with tunable size exhibit not only good thermostability, but also remarkable physiological stability that can resist the enzymatic degradation. As a novel siRNA delivery system with spherical nucleic acid (SNA) architecture, the crosslinked nanogels can assist the delivery of siRNAs into different cells without any transfection agents and achieve the gene silencing effectively both in vitro and in vivo, through which a significant inhibition of tumor growth is realized in the anticancer treatment.
功能性 siRNA 被用作连接子,通过核酸杂交将接枝有 DNA 的聚己内酯(DNA-g-PCL)刷引导自组装成球形和纳米级水凝胶,其中小干扰 RNA(siRNA)被完全嵌入和保护以进行系统传递。由于内部存在多价的相互交联事件,交联纳米凝胶具有可调节的尺寸,不仅表现出良好的热稳定性,而且具有显著的生理稳定性,可以抵抗酶的降解。作为一种具有球形核酸(SNA)结构的新型 siRNA 递送系统,交联纳米凝胶可以在没有任何转染试剂的情况下协助 siRNA 递送至不同的细胞,并在体外和体内有效地实现基因沉默,从而在癌症治疗中实现了肿瘤生长的显著抑制。