Abstract
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.
Original language | English (US) |
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Pages (from-to) | 199-212 |
Number of pages | 14 |
Journal | Journal of Controlled Release |
Volume | 105 |
Issue number | 3 |
DOIs | |
State | Published - Jul 20 2005 |
Externally published | Yes |
Bibliographical note
Funding Information:Financial support of portions of this work by the National Institute of Health (Grant RO1EB002047) and, in part, by U.S. Department of Energy (Grant DE-ACO3-76SF00098) for the development of stimuli responsive nanoparticles is acknowledged with thanks.
Keywords
- Adjuvant oligonucleotides
- Antigen presentation
- Cancer vaccine
- Degradable nanoparticle
- Dendritic cells
ASJC Scopus subject areas
- Pharmaceutical Science