Modulation of Dendritic Cell Function via Nanoparticle-Induced Cytosolic Calcium Changes
Zhengwei Cao, Xueyuan Yang, Wei Yang, Fanghui Chen, Wen Jiang, Shuyue Zhan, Fangchao Jiang, Jianwen Li, Chenming Ye, Liwei Lang, Sirui Zhang, Zhizi Feng, Xinning Lai, Yang Liu, Leidong Mao, Houjian Cai, Yong Teng, Jin Xie
Abstract
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.