Zhang Shiwen, Wang Changqiang, Jiang Jing, Li Linlu, Luo Jiaqi, Zhu Jingying, Chen Renxu
Department of the Head and Neck, The Third Affiliated Hospital of Kunming Medical University, Yunnan Cancer Hospital, Peking University Cancer Hospital Yunnan, Kunming, People's Republic of China.
Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, 210002, People's Republic of China.
J Inflamm Res. 2025 Sep 3;18:12089-12103. doi: 10.2147/JIR.S528371. eCollection 2025.
Immune escape of tumor cells is a common problem with tumor photothermal therapy utilizing gold nanorods (Au NRs). Whether CpG ODN, an immune adjuvant, can synergize with Au NRs to activate the immune response and its potential mechanism is not clear.
The effect of Au NRs combined with CpG ODN (Au NRs-C) on the activity of various immune-related cells, such as double-positive T cells, macrophages, NK cells, Th17, and Treg. The expression levels of various immune and inflammation-related factors, such as IL-1R1, IL-6, IL-17, and TNF-α were characterized. Transcriptome sequencing analysis was used to explore the potential immunomodulatory mechanisms of Au NRs-C. Whether immune activation was enhanced by antibody-functionalized Au NR upon binding to CpG ODN was assessed.
Flow cytometry and ELISA analyses indicate that both Au NRs and CpG ODN increase pro-inflammatory cytokine levels and immune activation. However, Au NRs-C demonstrated superior immune activation potential. Furthermore, Au NRs stimulate the expression of Treg, while Au NRs-C significantly inhibit this effect. This suggests that the conjugation of CpG ODN with Au NRs not only greatly enhances the immune activation but also compensates for some of their deficiencies in eliciting immune responses. Transcriptome sequencing uncovered DEGs mainly localized to immune and pro-inflammatory cytokine pathways. PPI analysis identified six hub genes: , and . Moreover, CpG conjugation with antibody functionalization- Au NRs enhances immune stimulation.
Au NRs-C promotes immune activation by eliciting changes in the activity of immune-associated cells and expression of inflammatory factors through multiple pathways, such as MHC antigen presentation and Toll-like receptor-mediated immune processes.
肿瘤细胞的免疫逃逸是利用金纳米棒（Au NRs）进行肿瘤光热治疗时常见的问题。免疫佐剂CpG ODN是否能与Au NRs协同激活免疫反应及其潜在机制尚不清楚。
研究Au NRs与CpG ODN联合（Au NRs-C）对双阳性T细胞、巨噬细胞、NK细胞、Th17和Treg等多种免疫相关细胞活性的影响。对IL-1R1、IL-6、IL-17和TNF-α等多种免疫和炎症相关因子的表达水平进行表征。采用转录组测序分析探索Au NRs-C潜在的免疫调节机制。评估抗体功能化的Au NR与CpG ODN结合后是否增强免疫激活。
流式细胞术和ELISA分析表明，Au NRs和CpG ODN均能提高促炎细胞因子水平并激活免疫反应。然而，Au NRs-C表现出更强的免疫激活潜力。此外，Au NRs刺激Treg的表达，而Au NRs-C显著抑制这种作用。这表明CpG ODN与Au NRs的结合不仅大大增强了免疫激活，还弥补了它们在引发免疫反应方面的一些不足。转录组测序发现差异表达基因主要定位于免疫和促炎细胞因子途径。蛋白质-蛋白质相互作用分析确定了六个枢纽基因： ， 和 。此外，CpG与抗体功能化的Au NRs结合可增强免疫刺激。
Au NRs-C通过引发免疫相关细胞活性变化和炎症因子表达变化，通过多种途径促进免疫激活，如MHC抗原呈递和Toll样受体介导的免疫过程。
