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Programmed nanoparticle-loaded microparticles for effective antigen/adjuvant delivery
Institution:1. Tianjin Key Laboratory of Biomaterial Research, Institute of Biomedical Engineering, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300192, China;2. School of Chemical Engineering and Technology, Hebei University of Technology, Tianjin, 300130, China;3. NHC Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, Chu Hsien-I Memorial Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin 300134, China;1. School of Energy and Environment, Southeast University, Nanjing 210096, China;2. Southeast University-Monash University Joint Research Institute, Suzhou, 215123, China;3. Department of Chemical Engineering, Monash University, Clayton, Vic 3800, Australia;4. School of Qilu Transportation, Shandong University, Jinan, 250002, China;5. School of Metallurgy, Northeastern University, Shenyang, 110819, China;1. Institute of Chemistry, Federal University of Goiás - UFG, Campus Samambaia, Goiânia, GO, 74690-900, Brazil;2. School of Chemical Engineering, Federal University of Uberlândia - UFU, Campus Santa Mônica, Uberlândia, MG, 38408-144, Brazil;1. Key Laboratory of Functional Polymer Materials of Ministry of Education, State Key Laboratory of Medicinal Chemical Biology, Institute of Polymer Chemistry and College of Chemistry, Nankai University, Tianjin 300071, PR China;2. Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300192, PR. China;1. State Key Laboratory of Coal Mine Disaster Dynamics and Control, Chongqing University, Chongqing 400044, China;2. College of Petroleum Engineering and Geosciences, King Fahd University of Petroleum and Minerals, Saudi Arabia;1. School of Mechanical Engineering, The University of Newcastle, Callaghan 2308, Australia;2. School of Chemical Engineering, The University of Queensland, St Lucia 4072, Australia;3. Centre for Bulk Solids and Particulate Technologies, Newcastle Institute for Energy and Resources, The University of Newcastle, Callaghan 2308, Australia
Abstract:A microscale vaccine containing SiO2 nanoparticles loaded in CaCO3 microparticles was constructed using the co-precipitation method. The antigen ovalbumin (OVA) was covalently conjugated with SiO2 nanoparticles, and these nanoparticles and CpG were co-encapsulated into CaCO3 microparticles, generating a vaccine with a size of approximately 5.2 μm. Scanning electron microscopy (SEM), energy-dispersive X-ray (EDX), elemental mapping, and Fourier transform infrared (FTIR) analyses confirmed the successful preparation of the microscale vaccine; the vaccine had good storage stability without sustained antigen release, and negligible cytotoxicity to dendritic cells (DCs) and macrophages. Compared to SiO2 nanoparticles, the microscale vaccine can significantly improve antigen/adjuvant uptake. DCs internalized the entire microscale vaccine into lysosomes via macropinocytosis, and an increase in antigen endo/lysosomal escape was observed by confocal laser scanning microscopy (CLSM). Specifically, DCs pulsed with the vaccine were fully mature, expressing high levels of costimulatory molecules (CD40, CD80, and CD86), MHC II, and MHC I and secreting high levels of proinflammatory cytokines (IL-12, TNF-α, IL-1β, and IL-6). In addition, the vaccine had good in vivo biocompatibility, could protect the antigen from rapid degradation, and increased the retention time in lymph nodes. SiO2 nanoparticles-in-CaCO3 microparticles were an excellent carrier for antigen and adjuvant delivery. Hopefully, this study can provide some information on the design of microscale carriers for vaccine delivery systems.
Keywords:Antigen delivery  Cross-presentation  Microparticle  Silica nanoparticle  Bone marrow dendritic cell
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