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  4. Polymer micelles with pyridyl disulfide-coupled antigen travel through lymphatics and show enhanced cellular responses following immunization
 
research article

Polymer micelles with pyridyl disulfide-coupled antigen travel through lymphatics and show enhanced cellular responses following immunization

Eby, Jackson K.
•
Dane, Karen Y.
•
O'Neil, Conlin P.
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2012
Acta Biomaterialia

Poly(ethylene glycol)-stabilized poly(propylene sulfide) core (PEG-PPS) nanoparticles (NPs) smaller than 50 nm efficiently travel to draining lymph nodes and interact with antigen-presenting cells (APCs) to induce potent immune responses following intradermal immunization. To determine if a similar system could be developed that could be more easily and reproducibly prepared and eliminated faster in vivo, we created block copolymers of PEG-bl-PPS capable of self-assembling into 25-35 nm micelles (MCs). Biodistribution studies showed that these MCs were able to travel to draining lymph nodes, where they preferentially interacted with APCs. To couple cysteine-containing antigens to the surface of the MCs, a new polymer was synthesized with a terminal pyridyl disulfide (PDS), forming PDS-PEG-bl-PPS-benzyl. When mice were immunized in conjunction with free CpG as an adjuvant, ovalbumin-conjugated MCs (MC-Ova) generated more (2.4-fold) Ova-specific CD8(+) T cells in the blood and higher (1.7-fold) interferon-gamma levels from splenocytes upon restimulation than in mice immunized with free Ova and CpG. When comparing this MC platform to our PEG-PPS NPs with disulfide-linked Ova, no significant differences were found in the measured responses. These results indicate that PDS-functionalized MCs are efficient antigen delivery vehicles that enhance immune responses compared to immunization with free protein. (C) 2012 Acts Materialia Inc. Published by Elsevier Ltd. All rights reserved.

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Type
research article
DOI
10.1016/j.actbio.2012.06.007
Web of Science ID

WOS:000307625900003

Author(s)
Eby, Jackson K.
Dane, Karen Y.
O'Neil, Conlin P.
Hirosue, Sachiko
Swartz, Melody A.  
Hubbell, Jeffrey A.  
Date Issued

2012

Publisher

Elsevier Sci Ltd

Published in
Acta Biomaterialia
Volume

8

Issue

9

Start page

3210

End page

3217

Subjects

Micelle

•

Self-assembly

•

Copolymer

•

Nanoparticle

•

Immunostimulation

Editorial or Peer reviewed

REVIEWED

Written at

EPFL

EPFL units
LMRP  
LLCB  
Available on Infoscience
February 27, 2013
Use this identifier to reference this record
https://infoscience.epfl.ch/handle/20.500.14299/89619
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