钙纳米颗粒靶向并激活 T 细胞以增强抗肿瘤功能

Calcium signaling plays a crucial role in the activation of T lymphocytes.

However, modulating calcium levels to control T cell activation in vivo remains a challenge. In this study, we investigate T cell activation using 12-myristate 13-acetate (PMA)-encapsulated CaCO 3 nanoparticles.

We find that anti-PD-1 antibody-conjugated CaCO 3 nanoparticles can be internalized by T cells via receptor-mediated endocytosis and then gradually release calcium. This results in an increase in cytosolic calcium, which triggers the activation of NFAT and NF-κB pathways, especially when the surface of the CaCO 3 nanoparticles is loaded with PMA.

Animal studies demonstrate that the PMA-loaded calcium nanoparticles enhance the activation and proliferation of cytotoxic T cells, leading to improved tumor suppression without additional toxicity. When tested in metastatic tumor models, T cells loaded with the calcium nanoparticles prior to adoptive cell transfer control tumor growth better, resulting in prolonged animal survival.

Our approach offers an alternative T cell activation strategy to potentiate immunotherapy by targeting a fundamental signaling pathway.