Enhanced antigen presentation and immunostimulation of dendritic cells using acid-degradable cationic nanoparticles

Young Jik Kwon, Stephany M. Standley, Sarah L. Goh, Jean Frechet*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

126 Scopus citations

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 languageEnglish (US)
Pages (from-to)199-212
Number of pages14
JournalJournal of Controlled Release
Volume105
Issue number3
DOIs
StatePublished - Jul 20 2005

Keywords

  • Adjuvant oligonucleotides
  • Antigen presentation
  • Cancer vaccine
  • Degradable nanoparticle
  • Dendritic cells

ASJC Scopus subject areas

  • Pharmaceutical Science

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