International Institute of Nanotechnology, ‡Department of Chemical and Biological Engineering, §Department of Chemistry, and ∥Department of Biomedical Engineering, Northwestern University , 2145 Sheridan Road, Evanston, Illinois 60208, United States.
J Am Chem Soc. 2017 Mar 29;139(12):4278-4281. doi: 10.1021/jacs.6b13359. Epub 2017 Mar 20.
A one-pot synthesis of micellar spherical nucleic acid (SNA) nanostructures using Pluronic F127 as a thermoresponsive template is reported. These novel constructs are synthesized in a chemically straightforward process that involves intercalation of the lipid tails of DNA amphiphiles (CpG motifs for TLR-9 stimulation) into the hydrophobic regions of Pluronic F127 micelles, followed by chemical cross-linking and subsequent removal of non-cross-linked structures. The dense nucleic acid shell of the resulting cross-linked micellar SNA enhances their stability in physiological media and facilitates their rapid cellular internalization, making them effective TLR-9 immunomodulatory agents. These constructs underscore the potential of SNAs in regulating immune response and address the relative lack of stability of noncovalent constructs.
采用普朗尼克 F127 作为热敏模板,报道了一种一锅法合成胶束球形核酸(SNA)纳米结构的方法。这些新型构建体是通过将 DNA 两亲物(TLR-9 刺激的 CpG 基序)的脂质尾巴插入普朗尼克 F127 胶束的疏水区,然后进行化学交联,再去除未交联的结构,在化学上直接的过程中合成的。所得交联胶束 SNA 的密集核酸壳增强了它们在生理介质中的稳定性,并促进了它们的快速细胞内化,使它们成为有效的 TLR-9 免疫调节剂。这些构建体强调了 SNA 在调节免疫反应方面的潜力,并解决了非共价构建体相对缺乏稳定性的问题。