In situ release of IL-2/IL-12 from SiO2-engineered dendritic cells for synergistic immunotherapy

Abstract

Herein, a synergistic therapy strategy of cytokine and dendritic cell (DC) vaccine was developed via the chemical conjugation of cytokine-loaded SiO₂ directly on the plasma membrane of DCs. Firstly, IL-2/IL-12-loaded SiO₂ was prepared and modified with MAL-PEG-NHS, and then coupled on the membrane of mature DCs through the coupling of –MAL and –SH groups. The large surface area and bimodal pores of SiO₂ endowed it with high cytokine loading capacity and entrapment efficiency (EE%), with EE_IL-2% of 95.8% and EE_IL-12% of 86.4%. SiO₂ was stably attached to the surface of DCs, and thus not internalized by mature DCs, and the SiO₂ conjugation blocked only 4.37% of the total available cell surface thiol groups. After SiO₂ attachment, the cell viability, membrane integrity and intracellular reactive oxygen species (ROS) of DCs were not affected. Furthermore, this strategy avoids the systemic toxicity of cytokines and improves the ability of DCs to target lymph nodes. IL-2 and IL-12 were only released locally around DCs, enabling the pseudo-autocrine stimulation of the transferred DCs in vivo. Moreover, the long-term anti-tumor protection in a B16 tumor model was demonstrated. This strategy is a facile and generalizable dendritic cell-based cancer immunotherapy strategy to augment bioavailability, while minimizing the side effects of cytokines.