title: The Effect of Superparamagnetic Iron Oxide Nanoparticle Surface Charge on Antigen Cross-Presentation.
abstract: Magnetic nanoparticles (NPs) of superparamagnetic iron oxide (SPIO) have been explored for different kinds of applications in biomedicine, mechanics, and information. Here, we explored the synthetic SPIO NPs as an adjuvant on antigen cross-presentation ability by enhancing the intracellular delivery of antigens into antigen presenting cells (APCs). Particles with different chemical modifications and surface charges were used to study the mechanism of action of antigen delivery. Specifically, two types of magnetic NPs, γFe2O3/APTS (3-aminopropyltrimethoxysilane) NPs and γFe2O3/DMSA (meso-2, 3-Dimercaptosuccinic acid) NPs, with the same crystal structure, magnetic properties, and size distribution were prepared. Then, the promotion of T-cell activation via dendritic cells (DCs) was compared among different charged antigen coated NPs. Moreover, the activation of the autophagy, cytosolic delivery of the antigens, and antigen degradation mediated by the proteasome and lysosome were measured. Our results indicated that positive charged γFe2O3/APTS NPs, but not negative charged γFe2O3/DMSA NPs, enhanced the cross-presentation ability of DCs. Increased cross-presentation ability induced by γFe2O3/APTS NPs was associated with increased cytosolic antigen delivery. On the contrary, γFe2O3/DMSA NPs was associated with rapid autophagy. Overall, our results suggest that antigen delivered in cytoplasm induced by positive charged particles is beneficial for antigen cross-presentation and T-cell activation. NPs modified with different chemistries exhibit diverse biological properties and differ greatly in their adjuvant potentials. Thus, it should be carefully considered many different effects of NPs to design effective and safe adjuvants.
authors.affiliation: Nanjing Stomatological Hospital, Medical School of Nanjing University, 30#, Zhongyang Road, Nanjing, 210008, People's Republic of China.|Laboratory of Cancer Immunobiology, Robert W. Franz Cancer Research Center, Earle A. Chiles Research Institute, Providence Cancer Center, Portland, OR, USA.
authors.forename: Yongbin
authors.initials: Y
authors.lastname: Mou
authors.affiliation: Laboratory of Cancer Immunobiology, Robert W. Franz Cancer Research Center, Earle A. Chiles Research Institute, Providence Cancer Center, Portland, OR, USA.|Minigene Pharmacy Laboratory, School of Life Science and Technology, China Pharmaceutical University, Nanjing, People's Republic of China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Xing
authors.affiliation: Laboratory of Cancer Immunobiology, Robert W. Franz Cancer Research Center, Earle A. Chiles Research Institute, Providence Cancer Center, Portland, OR, USA.|Medical School, Southeast University, Nanjing, People's Republic of China.
authors.forename: Hongyan
authors.initials: H
authors.lastname: Ren
authors.affiliation: Laboratory of Cancer Immunobiology, Robert W. Franz Cancer Research Center, Earle A. Chiles Research Institute, Providence Cancer Center, Portland, OR, USA.
authors.forename: Zhihua
authors.initials: Z
authors.lastname: Cui
authors.affiliation: State Key Laboratory of Molecule and Bimolecular Electronics, Jiangsu Provincial Laboratory for Biomaterials and Devices, Southeast University, Nanjing, People's Republic of China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Laboratory of Cancer Immunobiology, Robert W. Franz Cancer Research Center, Earle A. Chiles Research Institute, Providence Cancer Center, Portland, OR, USA.|Medical School, Southeast University, Nanjing, People's Republic of China.
authors.forename: Guangjie
authors.initials: G
authors.lastname: Yu
authors.affiliation: Cancer Research, Robert W. Franz Cancer Research Center, Earle A. Chiles Research Institute, Providence Cancer Center, 4805 NE Glisan Street, Portland, OR, 97213, USA.
authors.forename: Walter J
authors.initials: WJ
authors.lastname: Urba
authors.affiliation: Nanjing Stomatological Hospital, Medical School of Nanjing University, 30#, Zhongyang Road, Nanjing, 210008, People's Republic of China. qghu@nju.edu.cn.
authors.forename: Qingang
authors.identifier: http://orcid.org/0000-0003-3904-0563
authors.initials: Q
authors.lastname: Hu
authors.affiliation: Laboratory of Cancer Immunobiology, Robert W. Franz Cancer Research Center, Earle A. Chiles Research Institute, Providence Cancer Center, Portland, OR, USA. hhu@providence.org.
authors.forename: Hongming
authors.initials: H
authors.lastname: Hu
keywords: Adjuvant; Antigen cross-presentation; Dendritic cells; Superparamagnetic iron oxide