Cao Zhengwei, Yang Xueyuan, Yang Wei, Chen Fanghui, Jiang Wen, Zhan Shuyue, Jiang Fangchao, Li Jianwen, Ye Chenming, Lang Liwei, Zhang Sirui, Feng Zhizi, Lai Xinning, Liu Yang, Mao Leidong, Cai Houjian, Teng Yong, Xie Jin
Department of Chemistry, University of Georgia, Athens, Georgia 30602, United States.
Department of Hematology and Medical Oncology & Winship Cancer Institute, Emory University School of Medicine, Atlanta, Georgia 30322, United States.
ACS Nano. 2024 Mar 12;18(10):7618-7632. doi: 10.1021/acsnano.4c00550. Epub 2024 Feb 29.
Calcium nanoparticles have been investigated for applications, such as drug and gene delivery. Additionally, Ca serves as a crucial second messenger in the activation of immune cells. However, few studies have systematically studied the effects of calcium nanoparticles on the calcium levels and functions within immune cells. In this study, we explore the potential of calcium nanoparticles as a vehicle to deliver calcium into the cytosol of dendritic cells (DCs) and influence their functions. We synthesized calcium hydroxide nanoparticles, coated them with a layer of silica to prevent rapid degradation, and further conjugated them with anti-CD205 antibodies to achieve targeted delivery to DCs. Our results indicate that these nanoparticles can efficiently enter DCs and release calcium ions in a controlled manner. This elevation in cytosolic calcium activates both the NFAT and NF-κB pathways, in turn promoting the expression of costimulatory molecules, antigen-presenting molecules, and pro-inflammatory cytokines. In mouse tumor models, the calcium nanoparticles enhanced the antitumor immune response and augmented the efficacy of both radiotherapy and chemotherapy without introducing additional toxicity. Our study introduces a safe nanoparticle immunomodulator with potential widespread applications in cancer therapy.
钙纳米颗粒已被研究用于药物和基因递送等应用。此外，钙在免疫细胞激活过程中作为关键的第二信使。然而，很少有研究系统地研究钙纳米颗粒对免疫细胞内钙水平和功能的影响。在本研究中，我们探索了钙纳米颗粒作为一种载体将钙递送至树突状细胞（DCs）胞质溶胶并影响其功能的潜力。我们合成了氢氧化钙纳米颗粒，用一层二氧化硅包裹以防止快速降解，并进一步将它们与抗CD205抗体偶联以实现对DCs的靶向递送。我们的结果表明，这些纳米颗粒可以有效地进入DCs并以可控方式释放钙离子。胞质钙的这种升高激活了NFAT和NF-κB途径，进而促进共刺激分子、抗原呈递分子和促炎细胞因子的表达。在小鼠肿瘤模型中，钙纳米颗粒增强了抗肿瘤免疫反应，并提高了放疗和化疗的疗效，且未引入额外毒性。我们的研究引入了一种安全的纳米颗粒免疫调节剂，在癌症治疗中具有潜在的广泛应用。
