3.8 Article

Display of DNA on Nanoparticles for Targeting Antigen Presenting Cells

Journal

ACS BIOMATERIALS SCIENCE & ENGINEERING
Volume 3, Issue 4, Pages 496-501

Publisher

AMER CHEMICAL SOC
DOI: 10.1021/acsbiomaterials.7b00148

Keywords

CpG; oligonucleotide; dendritic cell targeting; polyethylene glycol; nanoparticle vaccine; E2; biodistribution

Funding

  1. National Institutes of Health [R21EB017995]
  2. National Cancer Institute of the National Institutes of Health [P30CA062203]
  3. University of California Cancer Research Coordinating Committee [UCCRCC-101868]

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Efficient delivery of antigens is of paramount concern in immunotherapies. We aimed to target antigen presenting cells (APCs) by conjugating CpG oligonucleotides to an E2 protein nanoparticle surface (CpG-PEG-E2). Compared to E2 alone, we observed 4-fold increase of in vitro APC uptake of CpG both CpG-PEG-E2 and E2 conjugated to non-CpG DNA. Furthermore, compared to E2-alone or E2 functionalized solely with polyethylene glycol (PEG), the CpG-PEG-E2 showed enhanced lymph node retention up to at least 48 h and 2-fold increase in APC uptake in vivo, parameters which are advantageous for vaccine success. This suggests that enhanced APC uptake of nanoparticles mediated by oligonucleotide display may help overcome delivery barriers in vaccine development.

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