PMID- 23220107
OWN - NLM
STAT- MEDLINE
DCOM- 20130802
LR  - 20191210
IS  - 1873-4995 (Electronic)
IS  - 0168-3659 (Linking)
VI  - 166
IP  - 2
DP  - 2013 Mar 10
TI  - Nanogel vaccines targeting dendritic cells: contributions of the surface 
      decoration and vaccine cargo on cell targeting and activation.
PG  - 95-105
LID - S0168-3659(12)00812-7 [pii]
LID - 10.1016/j.jconrel.2012.11.015 [doi]
AB  - Dendritic cells (DCs) play crucial roles in initiating and promoting immune 
      defences, providing a pivotal target for vaccines. Although 
      nanoparticle/nanogel-based delivery vehicles are showing potential for delivering 
      vaccines to the immune system, there is little information on their 
      characteristics of interaction with DCs. While particle uptake by DCs has been 
      shown, the mechanism of cell targeting has not been studied. Moreover, it is 
      still unclear how particle surface decoration influences the handling of such 
      vaccines by DCs. Accordingly, chitosan nanogels carrying a model antigen, 
      ovalbumin (ova), were analysed for interaction with and processing by DCs. 
      Nanogel surfaces decorated with alginate (alg) or mannosylated alginate 
      (alg-man), were used for targeting particular DC receptors. DC uptake of 
      particles was observed, being dependent on endosomal-based processes. Inhibiting 
      PI3-kinase or lipid raft activities impaired the uptake, which was only reduced, 
      indicating the involvement of more than one endocytic pathway; notably, this was 
      observed with both nanogel-delivered or free ova. Importantly, surface decoration 
      of particles was less influential on particle uptake, contrasting with the ova 
      cargo which played the major role. Such influence of the vaccine cargo has to 
      date been largely ignored. When receptors interacting directly with ova were 
      blocked, this altered the uptake of alg-nanogels and alg-man-nanogels carrying 
      ova. The nanogels did have an influential role, in that modulation of DC 
      functional activity owed more to the nanogel structure. Using an in vitro 
      restimulation assay with ova-specific lymphocytes, nanogel-delivered and free ova 
      were similarly effective at inducing specific antibody. Nanogel-delivered ova 
      with mannose surface decoration was superior to free ova for inducing 
      interferon-gamma production by T-lymphocytes. Together, the data demonstrates that 
      particle-based vaccine delivery should consider the influences of both the 
      surface decoration and the vaccine cargo; each can influence different aspects of 
      the interaction with DCs. Such combined influences are likely to impinge on the 
      characteristics of the immune response induced.
CI  - Copyright (c) 2012 Elsevier B.V. All rights reserved.
FAU - Thomann-Harwood, L J
AU  - Thomann-Harwood LJ
AD  - Institute of Virology and Immunoprophylaxis, 3147 Mittelhaeusern, Switzerland. 
      Lisa.Harwood@ivi.admin.ch
FAU - Kaeuper, P
AU  - Kaeuper P
FAU - Rossi, N
AU  - Rossi N
FAU - Milona, P
AU  - Milona P
FAU - Herrmann, B
AU  - Herrmann B
FAU - McCullough, K C
AU  - McCullough KC
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20121204
PL  - Netherlands
TA  - J Control Release
JT  - Journal of controlled release : official journal of the Controlled Release 
      Society
JID - 8607908
RN  - 0 (Alginates)
RN  - 0 (Excipients)
RN  - 0 (Nanogels)
RN  - 0 (Vaccines)
RN  - 0 (polyethylene glycol polyethyleneimine nanogel)
RN  - 3WJQ0SDW1A (Polyethylene Glycols)
RN  - 82115-62-6 (Interferon-gamma)
RN  - 9002-98-6 (Polyethyleneimine)
RN  - PHA4727WTP (Mannose)
SB  - IM
MH  - Alginates
MH  - Animals
MH  - Apoptosis/drug effects
MH  - B-Lymphocytes/drug effects/immunology
MH  - Chemistry, Pharmaceutical
MH  - Dendritic Cells/*immunology/metabolism
MH  - Drug Delivery Systems
MH  - Drug Design
MH  - Excipients
MH  - Interferon-gamma/pharmacology
MH  - Mannose
MH  - Microscopy, Fluorescence
MH  - Nanogels
MH  - Nanoparticles
MH  - *Polyethylene Glycols
MH  - *Polyethyleneimine
MH  - Surface Properties
MH  - Swine
MH  - T-Lymphocytes/drug effects/immunology
MH  - Vaccines/*administration & dosage
MH  - Viscosity
EDAT- 2012/12/12 06:00
MHDA- 2013/08/03 06:00
CRDT- 2012/12/11 06:00
PHST- 2012/09/11 00:00 [received]
PHST- 2012/11/23 00:00 [revised]
PHST- 2012/11/25 00:00 [accepted]
PHST- 2012/12/11 06:00 [entrez]
PHST- 2012/12/12 06:00 [pubmed]
PHST- 2013/08/03 06:00 [medline]
AID - S0168-3659(12)00812-7 [pii]
AID - 10.1016/j.jconrel.2012.11.015 [doi]
PST - ppublish
SO  - J Control Release. 2013 Mar 10;166(2):95-105. doi: 10.1016/j.jconrel.2012.11.015. 
      Epub 2012 Dec 4.