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

Cu 掺杂的 TiO2 纳米粒子可改善局部抗肿瘤免疫激活并优化树突状细胞疫苗策略

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作者:Evelien Hesemans #, Neshat Saffarzadeh #, Christy Maksoudian, Mukaddes Izci, Tianjiao Chu, Carla Rios Luci, Yuqing Wang, Hendrik Naatz, Sebastian Thieme, Cornelia Richter, Bella B Manshian, Suman Pokhrel, Lutz Mädler, Stefaan J Soenen

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 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.

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