Yeast 13-D-glucan functionalized graphene oxide for macrophage-targeted delivery of CpG oligodeoxynucleotides and synergistically enhanced antitumor immunity
Yeast 13-D-glucan functionalized graphene oxide for macrophage-targeted delivery of CpG oligodeoxynucleotides and synergistically enhanced antitumor immunity
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酵母β-D-葡聚糖功能化氧化石墨烯用于巨噬细胞靶向递送 CpG 寡脱氧核苷酸并协同增强抗肿瘤免疫力
DOI：
10.1016/j.ijbiomac.2023.123432
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发表时间：
2023-02-18
影响因子：
8.2
通讯作者：
Zhang, Huijie
中科院分区：
文献类型：
--
作者：
Cheng, Ting;Yan, Ting;Zhang, Huijie
免疫刺激性 CpG 寡脱氧核苷酸 (CpG ODN) 在癌症免疫治疗中显示出强大的潜力。然而，由于核酸酶快速降解和细胞摄取不足，CpG ODN 的治疗效果受到阻碍。将 CpG ODN 转染到抗原呈递细胞 (APC) 中对于增强其治疗功效并减少潜在副作用至关重要。在此，通过用酵母13-D-葡聚糖对氧化石墨烯（GO）进行功能化，制备了多功能CpG ODNs载体，并进一步研究了其在癌症免疫治疗中的潜力。 GO-13-D-葡聚糖保护 CpG ODN 免受核酸酶消化。 13-D-葡聚糖由于能够识别 dectin-1，赋予了递送系统针对巨噬细胞的靶向能力。因此，由于 dectin-1 介导的内吞作用，GO-13-D-葡聚糖增强了 CpG ODN 向 RAW264.7 细胞的递送。更重要的是，13-D-葡聚糖与 CpG ODN 协同作用，诱导抗肿瘤免疫。 GO-13-D-葡聚糖/CpG ODNs更有效地抑制肿瘤细胞的生长。这项工作提供了一种用于癌症免疫治疗的巨噬细胞靶向 CpG ODN 递送系统。图形摘要。
Immunostimulatory CpG oligodeoxynucleotides (CpG ODNs) show strong potential in cancer immunotherapy. However, therapeutic efficacy of CpG ODNs is hindered due to rapid nuclease degradation and insufficient cellular uptake. Transfecting CpG ODNs into antigen presenting cells (APCs) is vital to enhance their therapeutic efficacy while reduce the potential side effects. Herein, a multifunctional CpG ODNs vector was fabricated through functionalization of graphene oxide (GO) with yeast 13-D-glucan, and its potential in cancer immuno-therapy was further investigated. GO-13-D-glucan protected CpG ODNs from nuclease digestion. 13-D-glucan endowed the delivery system with targeting ability for macrophage due to its recognition with dectin-1. Thus, GO-13-D-glucan enhanced the delivery of CpG ODNs into RAW264.7 cells due to dectin-1-mediated endocytosis. More importantly, 13-D-glucan functioned synergistically with CpG ODNs in inducing antitumor immunity. GO-13-D-glucan/CpG ODNs inhibited the tumor cells growth more effectively. This work provides a macrophage -targeted CpG ODNs delivery system for cancer immunotherapy. Graphic abstract.