Bioconjug Chem. 2019 Jul 17;30(7):2032-2037. doi: 10.1021/acs.bioconjchem.9b00316. Epub 2019 Jun 19.
This paper describes how the ligand shell containing immunostimulatory oligonucleotides surrounding gold nanoparticles affects the activation of macrophages. Nanoconstructs with similar ligand densities but different oligonucleotide compositions (from 0% to 100% immune-active cytosine-phosphate-guanine, CpG) were compared. Maximum immunostimulation was achieved with CpG content as low as 5% (with total oligonucleotide surface coverage remaining constant), correlating to high levels of antitumor cytokine release and low levels of cancer-promoting ones. Independent of CpG content, gold nanoparticles with low oligonucleotide densities exhibit poor cellular uptake, leading to insignificant immunostimulation and cytokine release. By identifying effects of ligand shell composition on macrophage activation, we can inform the design rules of therapeutic nanoconstructs to achieve specific immune responses.
本文描述了含有免疫刺激性寡核苷酸的配体壳如何影响金纳米粒子对巨噬细胞的激活。比较了具有相似配体密度但具有不同寡核苷酸组成(从 0%到 100%免疫活性胞嘧啶-磷酸-鸟嘌呤,CpG)的纳米结构。具有低至 5%CpG 含量(保持总寡核苷酸表面覆盖率不变)的最大免疫刺激作用与高水平的抗肿瘤细胞因子释放和低水平的促癌细胞因子释放相关。独立于 CpG 含量,具有低寡核苷酸密度的金纳米粒子表现出较差的细胞摄取,导致免疫刺激和细胞因子释放不明显。通过确定配体壳组成对巨噬细胞激活的影响,我们可以为治疗性纳米结构的设计规则提供信息,以实现特定的免疫反应。