Cheng Ting, Yan Ting, Wu Jinwei, Wang Qi, Zhang Huijie
Department of Oncology, Wuxi No.2 People's Hospital, Wuxi 214000, China.
School of Biotechnology, Jiangnan University, Wuxi 214122, China.
Int J Biol Macromol. 2023 Apr 15;234:123432. doi: 10.1016/j.ijbiomac.2023.123432. Epub 2023 Jan 27.
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 β-D-glucan, and its potential in cancer immunotherapy was further investigated. GO-β-D-glucan protected CpG ODNs from nuclease digestion. β-D-glucan endowed the delivery system with targeting ability for macrophage due to its recognition with dectin-1. Thus, GO-β-D-glucan enhanced the delivery of CpG ODNs into RAW264.7 cells due to dectin-1-mediated endocytosis. More importantly, β-D-glucan functioned synergistically with CpG ODNs in inducing antitumor immunity. GO-β-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.
免疫刺激型CpG寡脱氧核苷酸（CpG ODNs）在癌症免疫治疗中显示出强大的潜力。然而，由于核酸酶的快速降解和细胞摄取不足，CpG ODNs的治疗效果受到阻碍。将CpG ODNs转染到抗原呈递细胞（APCs）中对于提高其治疗效果同时降低潜在副作用至关重要。在此，通过用酵母β-D-葡聚糖对氧化石墨烯（GO）进行功能化制备了一种多功能CpG ODNs载体，并进一步研究了其在癌症免疫治疗中的潜力。GO-β-D-葡聚糖保护CpG ODNs不被核酸酶消化。β-D-葡聚糖因其与dectin-1的识别而赋予递送系统对巨噬细胞的靶向能力。因此，由于dectin-1介导的内吞作用，GO-β-D-葡聚糖增强了CpG ODNs向RAW264.7细胞的递送。更重要的是，β-D-葡聚糖与CpG ODNs在诱导抗肿瘤免疫方面发挥协同作用。GO-β-D-葡聚糖/CpG ODNs更有效地抑制肿瘤细胞生长。这项工作为癌症免疫治疗提供了一种巨噬细胞靶向的CpG ODNs递送系统。图形摘要。
