Cu-doped TiO2 nanoparticles improve local antitumor immune activation and optimize dendritic cell vaccine strategies
Evelien Hesemans, Neshat Saffarzadeh, Christy Maksoudian, Mukaddes Izci, Tianjiao Chu, Carla Ríos‐Luci, Yuqing Wang, Hendrik Naatz, Sebastian Thieme, Cornelia Richter, Bella B. Manshian, Suman Pokhrel, Lutz Mädler, Stefaan J. Soenen
Abstract
Abstract 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 TiO 2 nanoparticles in order to tune the kinetics and full extent of Cu 2+ ion release from the remnant TiO 2 nanocrystals. Fine-tuning nanoparticle properties resulted in a formulation of 33% Cu-doped TiO 2 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. Graphical Abstract