Cu-doped TiO₂ nanoparticles improve local antitumor immune activation and optimize dendritic cell vaccine strategies

Nanoparticle-mediated cancer immunotherapy holds great promise, but more efforts are needed to obtain nanoformulations that result in a full scale activation of innate and adaptive immune components that specifically target the tumors. We generated a series of copper-doped TiO₂ nanoparticles in order to tune the kinetics and full extent of Cu²⁺ ion release from the remnant TiO₂ nanocrystals. Fine-tuning nanoparticle properties resulted in a formulation of 33% Cu-doped TiO₂ which enabled short-lived hyperactivation of dendritic cells and hereby promoted immunotherapy. The nanoparticles result in highly efficient activation of dendritic cells ex vivo, which upon transplantation in tumor bearing mice, exceeded the therapeutic outcomes obtained with classically stimulated dendritic cells. Efficacious but simple nanomaterials that can promote dendritic cancer cell vaccination strategies open up new avenues for improved immunotherapy and human health.