Antigen-Loaded Upconversion Nanoparticles for Dendritic Cell Stimulation, Tracking, and Vaccination in Dendritic Cell-Based Immunotherapy

Jian Xiang, Ligeng Xu,* HuaGong,Wenwen Zhu, ChaoWang, Jun Xu, Liangzhu Feng, Liang Cheng, Rui Peng,* and Zhuang Liu*

Institute of Functional Nano & Soft Materials (FUNSOM), Collaborative Innovation Center of Suzhou Nano Science and Technology, Soochow University, Suzhou, Jiangsu 215123, China

A dendritic cell (DC) vaccine, which is based on efficient antigen delivery into DCs and migration of antigen-pulsed DCs to draining lymph nodes after vaccination, is an effective strategy in initiating CD8þ T cell immunity for immunotherapy. Herein, antigen-loaded upconversion nanoparticles (UCNPs) are used to label and stimulate DCs, which could be precisely tracked after being injected into animals and induce an antigen-specific immune response. It is discovered that a model antigen, ovalbumin (OVA), could be adsorbed on the surface of dual-polymer-coated UCNPs via electrostatic interaction, forming nanoparticleantigen complexes, which are efficiently engulfed by DCs and induce DC maturation and cytokine release. Highly sensitive in vivo upconversion luminescence (UCL) imaging of nanoparticle-labeled DCs is successfully carried out, observing the homing of DCs to draining lymph nodes after injection. In addition, strong antigen-specific immune responses including enhanced T cell proliferation, interferon gamma (IFN-γ) production, and cytotoxic T lymphocyte (CTL)-mediated responses are induced by a nanoparticle-pulsed DC vaccine, which is promising for DC-based immunotherapy potentially against cancer.