title: Simultaneous in vivo tracking of dendritic cells and priming of an antigen-specific immune response.
abstract: We report the fabrication of a one-pot antigen system that delivers antigen to dendritic cells (DCs) and tracks their in vivo migration after injection. Multifunctional polymer nanoparticles containing ovalbumin protein, magnetic resonance imaging contrast agents (iron oxide nanoparticles), and near-infrared fluorophores (indocyanine green, ICG), MPN-OVA, were prepared using a double emulsion method. The MPN-OVA was efficiently taken up by the dendritic cells and subsequently localized in the lysosome. Flow cytometry analysis revealed an increase in the uptake of OVA antigen by MPN-OVA at 37 °C, when compared with soluble OVA protein. We found that MPN-OVA had no effect on DC surface expression of MHC class I, costimulatory (CD80, CD86) or adhesion (CD54) molecules or the ability of DCs to mature in response to LPS. Following the uptake of MPN-OVA, exogenous OVA antigen was delivered to the cytoplasm, and OVA peptides were presented on MHC class I molecules, which enhanced OVA antigen-specific cross-presentation to OT-1 T cells and CD8OVA1.3 T cell hybridoma in vitro. The immunization of mice with MPN-OVA-treated DCs induced OVA-specific CTL activity in draining lymph nodes. The presence of MPN allowed us to monitor the migration of DCs via lymphatic drainage using NIR fluorescence imaging, and the homing of DCs into the lymph nodes was imaged using MRI. This system has potential for use as a delivery system to induce T cell priming and to image DC-based immunotherapies.
authors.affiliation: BioNanotechnology Research Center, Korea Research Institute of Bioscience and Biotechnology, P.O. Box 115, Yuseong, Daejeon 305-806, South Korea.
authors.forename: Young-Woock
authors.initials: YW
authors.lastname: Noh
authors.forename: Yong-Suk
authors.initials: YS
authors.lastname: Jang
authors.forename: Kook-Jin
authors.initials: KJ
authors.lastname: Ahn
authors.forename: Yong Taik
authors.initials: YT
authors.lastname: Lim
authors.forename: Bong Hyun
authors.initials: BH
authors.lastname: Chung
mesh_terms: D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology*; D005434:Flow Cytometry; D007208:Indocyanine Green / Q000737:chemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D053758:Nanoparticles / Q000737:chemistry*; D010047:Ovalbumin / Q000737:chemistry / Q000276:immunology; D011108:Polymers / Q000737:chemistry; D013601:T-Lymphocytes / Q000166:cytology / Q000378:metabolism
chemical_list: D011108:Polymers; D010047:Ovalbumin; D007208:Indocyanine Green