Abstract 388: Antigen-loaded Fe3O4 nanoparticles for the stimulation and tracking of dendritic cell based vaccine

Abstract

Abstract Background and purpose:Dendritic cells (DCs), as the antigen-presenting cells, play important roles in immunotherapy. The antigen uptake, cross-presentation, maturation and lymph node migration of DCs are crucial steps for immune system activation. Herein, we aim to construct a novel Fe3O4@SIINFEKL-TAT nanoparticle, which mainly consists of Fe3O4 nanosphere core and transmembrane peptide TAT on the shell, and also with the model antigen SIINFEKL peptide, a peptide of the ovalbumin (OVA) antigen. To explore the feasibility of Fe3O4@OVA-TAT to stimulate the maturation of DCs and the in vivo tracking of DCs using MRI-MPI dual-modal imaging. Methods: On the one hand, TAT peptide facilitates the uptake of the Fe3O4@OVA-TAT nanoparticles into DCs, and subsequently the OVA antigens are cross-presented to stimulate DCs maturation. On the other hand, Fe3O4 nanosphere core can function for both magnetic resonance imaging (MRI) and magnetic particle imaging (MPI) dual-modality imaging, which can realize the in vivo dynamic tracking of DCs migration to lymph nodes. Results: The laser confocal microscope experiments confirmed that Fe3O4@OVA-TAT can be taken up through the early endosome-late endosome pathway, but the fluorescent signal of the imaging probe is located outside the lysosome after 4 h, which suggested that Fe3O4@OVA-TAT could escape lysosomal uptake and cross-present. The CD80 and CD86 flow cytometry results showed that Fe3O4@OVA-TAT, LPS, and OVA can stimulate 90%, 60%, and 40% of BMDCs to mature, respectively (p < 0.05). After the Fe3O4@SIINFEKL-TAT labeled DCs was injected into the mouse footpad, the MRI T2WI signal decreased and the MPI signal increased in the popliteal and inguinal lymph nodes 24 h post-injection, suggesting that our DC vaccine can efficiently migrate to the lymph node. Conclusions: Our study showed that Fe3O4@SIINFEKL-TAT nanoparticles can stimulate and trace DCs in in vivo, which pave the way for further development and precision application of DC vaccine in both preclinical and clinical settings. Citation Format: Yafei Qi, Yang Du, Jie Tian, Zhengyu Jin, Yuan Li. Antigen-loaded Fe3O4 nanoparticles for the stimulation and tracking of dendritic cell based vaccine [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 388.