PMID- 37598888
OWN - NLM
STAT- Publisher
LR  - 20231012
IS  - 1873-4995 (Electronic)
IS  - 0168-3659 (Linking)
VI  - 362
DP  - 2023 Oct
TI  - Impact of interferon-gamma on the target cell tropism of nanoparticles.
PG  - 325-341
LID - S0168-3659(23)00534-5 [pii]
LID - 10.1016/j.jconrel.2023.08.034 [doi]
AB  - Interferon-gamma (IFN-gamma) is well known to reduce the infectivity of viral pathogens 
      by altering their tissue tropism. This effect is induced by upregulation of 
      cholesterol 25-hydroxylase (CH25H). Given the similarity of viral pathogens and 
      ligand-functionalized nanoparticles in the underlying strategy of 
      receptor-mediated cell recognition, it appears conceivable that IFN-gamma exceeds 
      similar effects on nanoparticles. Concretely, IFN-gamma-induced activation of CH25H 
      could decrease nanoparticle avidity for target cells via depletion of 
      clathrin-coated pits. We hypothesized that this effect would cause deterioration 
      of target-cell specific accumulation of nanoparticles. To prove our hypothesis, 
      we investigated the cell tropism of angiotensin II functionalized nanoparticles 
      (NP(Lys-Ang II)) in a co-culture system of angiotensin II subtype 1 receptor 
      (AT(1)R) positive rat mesangial target cells (rMCs) and AT(1)R-negative HeLa 
      off-target cells. In the presence of IFN-gamma we observed an up to 5-fold loss of 
      target cell preference for NP(Lys-Ang II). Thus, our in vitro results suggest a 
      strong influence of IFN-gamma on nanoparticle distribution, which is relevant in the 
      context of nanotherapeutic approaches to cancer treatment, as IFN-gamma is strongly 
      expressed in tumors. For the target cell tropism of viruses, our results provide 
      a conclusive hypothesis for the underlying mechanism behind non-directed viral 
      distribution in the presence of IFN-gamma.
CI  - Copyright (c) 2023 Elsevier B.V. All rights reserved.
FAU - Zimmer, Oliver
AU  - Zimmer O
AD  - Department of Pharmaceutical Technology, University of Regensburg, Regensburg, 
      Bavaria 93053, Germany.
FAU - Walter, Melanie
AU  - Walter M
AD  - Department of Pharmaceutical Technology, University of Regensburg, Regensburg, 
      Bavaria 93053, Germany.
FAU - Remmert, Marius
AU  - Remmert M
AD  - Department of Pharmaceutical Technology, University of Regensburg, Regensburg, 
      Bavaria 93053, Germany.
FAU - Maier, Olga
AU  - Maier O
AD  - Institute for Molecular and Cellular Anatomy, University of Regensburg, 
      Regensburg, Bavaria 93053, Germany.
FAU - Witzgall, Ralph
AU  - Witzgall R
AD  - Institute for Molecular and Cellular Anatomy, University of Regensburg, 
      Regensburg, Bavaria 93053, Germany.
FAU - Goepferich, Achim
AU  - Goepferich A
AD  - Department of Pharmaceutical Technology, University of Regensburg, Regensburg, 
      Bavaria 93053, Germany. Electronic address: achim.goepferich@ur.de.
LA  - eng
PT  - Journal Article
DEP - 20230902
PL  - Netherlands
TA  - J Control Release
JT  - Journal of controlled release : official journal of the Controlled Release 
      Society
JID - 8607908
SB  - IM
OTO - NOTNLM
OT  - Biodistribution
OT  - Cholesterol-25-hydroxylase (CH25H)
OT  - Interferon-gamma
OT  - Nano-bio interactions
OT  - Preferential uptake
OT  - Targeted nanoparticles
OT  - Targeting efficiency
COIS- Conflicts of interest There are no conflicts of interest to declare.
EDAT- 2023/08/21 00:41
MHDA- 2023/08/21 00:41
CRDT- 2023/08/20 19:26
PHST- 2023/04/17 00:00 [received]
PHST- 2023/08/04 00:00 [revised]
PHST- 2023/08/16 00:00 [accepted]
PHST- 2023/08/21 00:41 [pubmed]
PHST- 2023/08/21 00:41 [medline]
PHST- 2023/08/20 19:26 [entrez]
AID - S0168-3659(23)00534-5 [pii]
AID - 10.1016/j.jconrel.2023.08.034 [doi]
PST - ppublish
SO  - J Control Release. 2023 Oct;362:325-341. doi: 10.1016/j.jconrel.2023.08.034. Epub 
      2023 Sep 2.