用于增强 CpG 寡脱氧核苷酸介导的抗肿瘤免疫的阳离子淀粉纳米颗粒。
Cationic Starch Nanoparticles for Enhancing CpG Oligodeoxynucleotide-Mediated Antitumor Immunity.
发表日期:2023 Nov 13
作者:
Jiawen Zhang, Shuo Wang, Honghui Huang, Hongqian Chen, Jinghua Chen, Huijie Zhang
来源:
BIOMACROMOLECULES
摘要:
CpG ODN 展示了免疫治疗的重大前景。然而,由于 DNA 酶快速消化和细胞内化不足,它们的应用受到限制。将 CpG ODN 转运至免疫细胞至关重要。尽管病毒载体具有较高的转染效率,但安全风险、成本高、运载能力低仍然是一大障碍。在此,利用淀粉制备了一种新型的 CpG ODNs 载体。淀粉经超声处理后接枝二乙烯三胺简单胺化(NH2-St),呈直径50 nm的球形。 NH2-St具有良好的生物相容性。阳离子NH2-St很好地封装了CpG ODN,并具有317 μg/mg的高负载量。 NH2-St 保护 CpG ODN 免受核酸酶消化,并显着增强其细胞摄取。 NH2-St/CpG 诱导巨噬细胞有效分泌抗肿瘤细胞因子,有效抑制肿瘤细胞的生长。这项工作凸显了淀粉在 CpG ODN 递送方面的前景,这为癌症免疫治疗带来了新的希望。
CpG ODNs demonstrate a significant promise for immunotherapy. However, their application is limited owing to quick DNase digestion and inadequate cellular internalization. Transportation of CpG ODNs into immune cells is crucial. Although viral vectors exhibit high transfection efficiency, safety risks, high cost, and low carrying capacity remain big obstacles. Herein, a novel CpG ODNs vector was fabricated by using starch. Starch was ultrasonicated and simply aminated (NH2-St) through grafting with diethylenetriamine, which was spherical with a diameter of 50 nm. NH2-St possessed good biocompatibility. Cationic NH2-St encapsulated CpG ODNs well and possessed a high loading capacity of 317 μg/mg. NH2-St protected CpG ODNs from nuclease digestion and significantly enhanced their cellular uptake. NH2-St/CpG induced the potent secretion of antitumor cytokines from macrophages and effectively suppressed the growth of tumor cells. This work highlights the promise of starch for CpG ODNs delivery, which brings new hope for cancer immunotherapy.