Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University , 200030 Shanghai, China.
CAS Key Laboratory of Nanosystem and Hierarchical Fabrication, CAS Center for Excellence in Nanoscience, National Center for NanoScience and Technology , 11 BeiYiTiao, ZhongGuanCun, 100190 Beijing, China.
ACS Appl Mater Interfaces. 2017 Jun 21;9(24):20324-20329. doi: 10.1021/acsami.7b05890. Epub 2017 Jun 6.
Dendrimer-like DNA nanostructures have attractive properties such as mechanical stability, highly branched nanostructure, customized sizes, and biocompatibility. In this study, we construct programmable DNA dendrimeric nanoparticles as efficient vehicles to deliver immunostimulatory cytosine-phosphate-guanosine (CpG) sequences for activation of the immune response. DNA dendrimers decorated with CpG-containing hairpin-loops triggered stronger immune response characterized by pro-inflammatory cytokines production, in contrast to DNA dendrimers loading linear CpG. After further modification with TAT peptide, a typical cell-penetrating peptide, on the surface of the nanocarriers, CpG loops-loaded DNA dendrimers showed the enhanced cell internalization and cytokines production. The TAT-DNA dendrimer-CpG loops constructs did not affect the viability of immune cells and no detectable cytotoxicity was observed. Our results demonstrate that the DNA dendrimers can serve as designable and safe vehicles for delivery of immune modulators and anticancer drugs.
树状大分子样 DNA 纳米结构具有机械稳定性、高度分支的纳米结构、定制尺寸和生物相容性等吸引人的特性。在这项研究中，我们构建了可编程 DNA 树突状纳米颗粒作为有效的载体，将免疫刺激性胞嘧啶-磷酸-鸟嘌呤（CpG）序列递送至免疫反应的激活。用含有 CpG 的发夹环修饰的 DNA 树突状聚合物触发了更强的免疫反应，表现为促炎细胞因子的产生，而与负载线性 CpG 的 DNA 树突状聚合物相比。在纳米载体表面进一步用 TAT 肽（一种典型的细胞穿透肽）修饰后，负载 CpG 环的 DNA 树突状聚合物显示出增强的细胞内化和细胞因子产生。TAT-DNA 树突状聚合物-CpG 环构建物不影响免疫细胞的活力，并且没有观察到明显的细胞毒性。我们的结果表明，DNA 树突状聚合物可用作设计合理且安全的载体，用于递送免疫调节剂和抗癌药物。
