Self-Assembled DNA Dendrimer Nanoparticle for Efficient Delivery of Immunostimulatory CpG Motifs
Self-Assembled DNA Dendrimer Nanoparticle for Efficient Delivery of Immunostimulatory CpG Motifs
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DOI：
10.1021/acsami.7b05890
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发表时间：
2017-06-21
影响因子：
9.5
通讯作者：
Ding, Baoquan
中科院分区：
文献类型：
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作者：
Qu, Yijiao;Yang, Juanjuan;Ding, Baoquan
树突状DNA纳米结构具有机械稳定性、高度分支纳米结构、定制尺寸和生物相容性等吸引人的特性。在这项研究中，我们构建了可编程的DNA树状纳米颗粒，作为有效的载体，递送免疫刺激胞嘧啶-磷酸-鸟苷（CpG）序列，以激活免疫反应。与加载线性CpG的DNA树状大分子相比，用含有CpG的发卡环修饰的DNA树状大分子引发了更强的免疫反应，其特征是促炎细胞因子的产生。在纳米载体表面进一步使用TAT肽（一种典型的细胞穿透肽）修饰后，CpG环负载的DNA树状大分子显示出增强的细胞内化和细胞因子产生。TAT-DNA树突- cpg环结构不影响免疫细胞的活力，也未观察到可检测到的细胞毒性。我们的研究结果表明，DNA树状大分子可以作为免疫调节剂和抗癌药物递送的设计和安全的载体。
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 nano particles 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.