title: Different-Sized Gold Nanoparticle Activator/Antigen Increases Dendritic Cells Accumulation in Liver-Draining Lymph Nodes and CD8+ T Cell Responses.
abstract: The lack of efficient antigen and activator delivery systems, as well as the restricted migration of dendritic cells (DCs) to secondary lymph organs, dramatically limits DC-based adoptive immunotherapy. We selected two spherical gold nanoparticle (AuNP)-based vehicles of optimal size for activator and antigen delivery. Their combination (termed the NanoAu-Cocktail) was associated with the dual targeting of CpG oligonucleotides (CpG-ODNs) and an OVA peptide (OVAp) to DC subcellular compartments, inducing enhanced antigen cross-presentation, upregulated expression of costimulatory molecules and elevated secretion of T helper1 cytokines. We demonstrated that the intravenously transfused NanoAu-Cocktail pulsed DCs showed dramatically improved in vivo homing ability to lymphoid tissues and were settled in T cell area. Especially, by tissue-distribution analysis, we found that more than 60% of lymphoid tissues-homing DCs accumulated in liver-draining lymph nodes (LLNs). The improved homing ability of NanoAu-Cocktail pulsed DCs was associated with the high expression of chemokine receptor 7 (CCR7) and rearrangement of the cytoskeletons. In addition, by antigen-specific tetramers detection, NanoAu-Cocktail pulsed DCs were proved able to elicit strong antigen-specific CD8+ T cell responses, which provided enhanced protection from viral invasions. This study highlights the importance of codelivering antigen/adjuvant using different sized gold nanoparticles to improve DC homing and therapy.
authors.affiliation: Beijing Institute of Transfusion Medicine , Beijing Key Laboratory of Blood Safety and Supply Technologies, TaiPing Road 27, 100039 Beijing, P. R. China.
authors.forename: Qianqian
authors.initials: Q
authors.lastname: Zhou
authors.affiliation: Beijing Institute of Transfusion Medicine , Beijing Key Laboratory of Blood Safety and Supply Technologies, TaiPing Road 27, 100039 Beijing, P. R. China.
authors.forename: Yulong
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Beijing Institute of Transfusion Medicine , Beijing Key Laboratory of Blood Safety and Supply Technologies, TaiPing Road 27, 100039 Beijing, P. R. China.
authors.forename: Juan
authors.initials: J
authors.lastname: Du
authors.affiliation: Beijing Institute of Transfusion Medicine , Beijing Key Laboratory of Blood Safety and Supply Technologies, TaiPing Road 27, 100039 Beijing, P. R. China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Beijing Institute of Transfusion Medicine , Beijing Key Laboratory of Blood Safety and Supply Technologies, TaiPing Road 27, 100039 Beijing, P. R. China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Beijing Institute of Transfusion Medicine , Beijing Key Laboratory of Blood Safety and Supply Technologies, TaiPing Road 27, 100039 Beijing, P. R. China.
authors.forename: Qiuxia
authors.initials: Q
authors.lastname: Fu
authors.affiliation: Beijing Institute of Transfusion Medicine , Beijing Key Laboratory of Blood Safety and Supply Technologies, TaiPing Road 27, 100039 Beijing, P. R. China.
authors.forename: Jingang
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Beijing Institute of Transfusion Medicine , Beijing Key Laboratory of Blood Safety and Supply Technologies, TaiPing Road 27, 100039 Beijing, P. R. China.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Wang
authors.affiliation: Beijing Institute of Transfusion Medicine , Beijing Key Laboratory of Blood Safety and Supply Technologies, TaiPing Road 27, 100039 Beijing, P. R. China.
authors.forename: Linsheng
authors.initials: L
authors.lastname: Zhan
mesh_terms: D000818:Animals; D000941:Antigens / Q000008:administration & dosage* / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology*; D006046:Gold / Q000737:chemistry; D007155:Immunologic Factors / Q000008:administration & dosage* / Q000276:immunology; D007167:Immunotherapy / Q000379:methods; D008099:Liver / Q000276:immunology; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology*; D008297:Male; D053768:Metal Nanoparticles / Q000737:chemistry*; D051379:Mice; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology; D010446:Peptide Fragments / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology
chemical_list: D000941:Antigens; D007155:Immunologic Factors; D010446:Peptide Fragments; D006046:Gold; D010047:Ovalbumin
keywords: dendritic cells; gold nanoparticles; immunotherapy; migration