PMID- 29157965
OWN - NLM
STAT- MEDLINE
DCOM- 20180829
LR  - 20181202
IS  - 1873-3476 (Electronic)
IS  - 0378-5173 (Linking)
VI  - 535
IP  - 1-2
DP  - 2018 Jan 15
TI  - Polymer-based nanoparticles loaded with a TLR7 ligand to target the lymph node 
      for immunostimulation.
PG  - 444-451
LID - S0378-5173(17)31086-4 [pii]
LID - 10.1016/j.ijpharm.2017.11.031 [doi]
AB  - Small-molecule agonists for the Toll-like receptors (TLR) 7 and 8 are effective 
      for the immunotherapy of skin cancer when used as topical agents. Their systemic 
      use has however been largely unsuccessful due to dose-limiting toxicity. We 
      propose a polymer-based nanodelivery system to target resiquimod, a TLR7 ligand, 
      to the lymph node in order to focus the immunostimulatory activity and to prevent 
      a generalized inflammatory response. We demonstrate successful encapsulation of 
      resiquimod in methoxypoly(ethylene glycol)-b-poly(DL-lactic acid) (mPEG-PLA) and 
      mixed poly(DL-lactic-co-glycolic acid) (PLGA)/mPEG-PLA nanoparticles. We show 
      that these particles are taken up mainly by dendritic cells and macrophages, 
      which are the prime initiators of anticancer immune responses. Nanoparticles 
      loaded with resiquimod activate these cells, demonstrating the availability of 
      the immune-stimulating cargo. The unloaded particles are non-inflammatory and do 
      not have cytotoxic activity on immune cells. Following subcutaneous injection in 
      mice, mPEG-PLA and PLGA/mPEG-PLA nanoparticles are detected in dendritic cells 
      and macrophages in the draining lymph nodes, demonstrating the targeting 
      potential of these particles. Thus, polymer-based nanoparticles represent a 
      promising delivery system that allows lymph node targeting for small-molecule 
      TLR7 agonists in the context of systemic cancer immunotherapy.
CI  - Copyright (c) 2017 Elsevier B.V. All rights reserved.
FAU - Widmer, Jerome
AU  - Widmer J
AD  - Department of Medicine, Faculty of Science, University of Fribourg, Chemin Du 
      Musee 5, 1700 Fribourg, Switzerland.
FAU - Thauvin, Cedric
AU  - Thauvin C
AD  - School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, 
      Rue Michel-Servet 1, 1211 Geneva, Switzerland.
FAU - Mottas, Ines
AU  - Mottas I
AD  - Department of Medicine, Faculty of Science, University of Fribourg, Chemin Du 
      Musee 5, 1700 Fribourg, Switzerland; School of Pharmaceutical Sciences, 
      University of Geneva, University of Lausanne, Rue Michel-Servet 1, 1211 Geneva, 
      Switzerland.
FAU - Nguyen, Van Nga
AU  - Nguyen VN
AD  - School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, 
      Rue Michel-Servet 1, 1211 Geneva, Switzerland.
FAU - Delie, Florence
AU  - Delie F
AD  - School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, 
      Rue Michel-Servet 1, 1211 Geneva, Switzerland.
FAU - Allemann, Eric
AU  - Allemann E
AD  - School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, 
      Rue Michel-Servet 1, 1211 Geneva, Switzerland. Electronic address: 
      eric.allemann@unige.ch.
FAU - Bourquin, Carole
AU  - Bourquin C
AD  - Department of Medicine, Faculty of Science, University of Fribourg, Chemin Du 
      Musee 5, 1700 Fribourg, Switzerland; School of Pharmaceutical Sciences, 
      University of Geneva, University of Lausanne, Rue Michel-Servet 1, 1211 Geneva, 
      Switzerland. Electronic address: carole.bourquin@unige.ch.
LA  - eng
PT  - Journal Article
DEP - 20171120
PL  - Netherlands
TA  - Int J Pharm
JT  - International journal of pharmaceutics
JID - 7804127
RN  - 0 (Imidazoles)
RN  - 0 (Ligands)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Polyesters)
RN  - 0 (Tlr7 protein, mouse)
RN  - 0 (Toll-Like Receptor 7)
RN  - 0 (methoxy poly(ethylene glycol)-poly(lactide))
RN  - 1SIA8062RS (Polylactic Acid-Polyglycolic Acid Copolymer)
RN  - 26009-03-0 (Polyglycolic Acid)
RN  - 33X04XA5AT (Lactic Acid)
RN  - 3WJQ0SDW1A (Polyethylene Glycols)
RN  - V3DMU7PVXF (resiquimod)
SB  - IM
MH  - Animals
MH  - Cell Line
MH  - Cell Survival/drug effects
MH  - Imidazoles/administration & dosage/chemistry
MH  - Immunization/*methods
MH  - Lactic Acid/*administration & dosage/chemistry
MH  - Ligands
MH  - Lymph Nodes/*metabolism
MH  - Macrophages/metabolism
MH  - Membrane Glycoproteins/metabolism
MH  - Mice, Inbred C57BL
MH  - Nanoparticles/*administration & dosage/chemistry
MH  - Polyesters/*administration & dosage/chemistry
MH  - Polyethylene Glycols/*administration & dosage/chemistry
MH  - Polyglycolic Acid/*administration & dosage/chemistry
MH  - Polylactic Acid-Polyglycolic Acid Copolymer
MH  - Spleen/cytology
MH  - Toll-Like Receptor 7/metabolism
OTO - NOTNLM
OT  - Immunostimulation
OT  - Nanoparticle
OT  - Resiquimod
OT  - TLR7
EDAT- 2017/11/22 06:00
MHDA- 2018/08/30 06:00
CRDT- 2017/11/22 06:00
PHST- 2017/09/23 00:00 [received]
PHST- 2017/11/15 00:00 [revised]
PHST- 2017/11/16 00:00 [accepted]
PHST- 2017/11/22 06:00 [pubmed]
PHST- 2018/08/30 06:00 [medline]
PHST- 2017/11/22 06:00 [entrez]
AID - S0378-5173(17)31086-4 [pii]
AID - 10.1016/j.ijpharm.2017.11.031 [doi]
PST - ppublish
SO  - Int J Pharm. 2018 Jan 15;535(1-2):444-451. doi: 10.1016/j.ijpharm.2017.11.031. 
      Epub 2017 Nov 20.