Enhanced antigen presentation and immunostimulation of dendritic cells using acid-degradable cationic nanoparticles.
Acid-degradable cationic nanoparticles encapsulating a model antigen (i.e., ovalbumin) were prepared by inverse microemulsion polymerization with acid-cleavable acetal cross-linkers. Incubation of these degradable nanoparticles with dendritic cells derived from bone marrow (BMDCs) resulted in the enhanced presentation of ovalbumin-derived peptides, as quantified by B3Z cells, a CD8+ T cell hybridoma. The cationic nature of the particles contributed to the increased surface endocytosis (or phagocytosis) observed with BMDCs, which is the first barrier to overcome for successful antigen delivery. The acid sensitivity of the particles served to direct more ovalbumin antigens to be processed into the appropriately trimmed peptide fragments and presented via the major histocompatibility complex (MHC) class I pathway following hydrolysis within the acidic lysosomes. It was also shown that adjuvant molecules such as unmethylated CpG oligonucleotides (CpG ODN) and anti-interleukin-10 oligonucleotides (AS10 ODN) could be co-delivered with the protein antigen for maximized cellular immune response.
Kwon
Young Jik
YJ
Center for New Directions in Organic Synthesis, University of California, Berkeley, CA 94720, United States.
Standley
Stephany M
SM
Goh
Sarah L
SL
Fréchet
Jean M J
JM
D000143:Acids; D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D017951:Antigen Presentation / Q000187:drug effects*; D001854:Bone Marrow Cells / Q000187:drug effects; D002412:Cations / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D018899:CpG Islands; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology*; D004705:Endocytosis / Q000187:drug effects; D005260:Female; D005805:Genes, MHC Class I / Q000276:immunology; D006863:Hydrogen-Ion Concentration; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D008863:Microspheres; D009841:Oligonucleotides / Q000008:administration & dosage / Q000737:chemistry; D010047:Ovalbumin / Q000276:immunology; D010316:Particle Size; D010455:Peptides / Q000276:immunology
D000143:Acids; D000276:Adjuvants, Immunologic; D002412:Cations; D009841:Oligonucleotides; D010455:Peptides; D016753:Interleukin-10; D010047:Ovalbumin