The Peptide/Antibody-Based Surface Decoration of Calcium Phosphate Nanoparticles Carrying siRNA Influences the p65 NF-κB Protein Expression in Inflamed Cells In Vitro

Earlier studies with nanoparticles carrying siRNA were restricted to investigating the inhibition of target-specific protein expression, while almost ignoring effects related to the nanoparticle composition. Here, we demonstrate how the design and surface decoration of nanoparticles impact the p65 n...

Full description

Bibliographic Details
Main Authors: Elena K. Müller, Nataniel Białas, Matthias Epple, Ingrid Hilger
Format: Article
Language:English
Published: MDPI AG 2022-07-01
Series:Biomedicines
Subjects:
Online Access:https://www.mdpi.com/2227-9059/10/7/1571
_version_ 1827597896551235584
author Elena K. Müller
Nataniel Białas
Matthias Epple
Ingrid Hilger
author_facet Elena K. Müller
Nataniel Białas
Matthias Epple
Ingrid Hilger
author_sort Elena K. Müller
collection DOAJ
description Earlier studies with nanoparticles carrying siRNA were restricted to investigating the inhibition of target-specific protein expression, while almost ignoring effects related to the nanoparticle composition. Here, we demonstrate how the design and surface decoration of nanoparticles impact the p65 nuclear factor-kappa B (NF-κB) protein expression in inflamed leucocytes and endothelial cells in vitro. We prepared silica-coated calcium phosphate nanoparticles carrying encapsulated siRNA against p65 NF-κB and surface-decorated with peptides or antibodies. We show that RGD-decorated nanoparticles are efficient in down-regulating p65 NF-κB protein expression in endothelial cells as a result of an enhanced specific cellular binding and subsequent uptake of nanoparticles. In contrast, nanoparticles decorated with IgG (whether specific or not for CD69) are efficient in down-regulating p65 NF-κB protein expression in T-cells, but not in B-cells. Thus, an optimized nanoparticle decoration with xenogenic IgG may stimulate a specific cellular uptake. In summary, the composition of siRNA-loaded calcium phosphate nanoparticles can either weaken or stimulate p65 NF-κB protein expression in targeted inflamed leucocytes and endothelial cells. In general, unveiling such interactions may be very useful for the future design of anti-p65 siRNA-based nanomedicines for treatment of inflammation-associated diseases.
first_indexed 2024-03-09T03:40:50Z
format Article
id doaj.art-d1a9cbb3e4d1461b8560e217c526bff7
institution Directory Open Access Journal
issn 2227-9059
language English
last_indexed 2024-03-09T03:40:50Z
publishDate 2022-07-01
publisher MDPI AG
record_format Article
series Biomedicines
spelling doaj.art-d1a9cbb3e4d1461b8560e217c526bff72023-12-03T14:41:39ZengMDPI AGBiomedicines2227-90592022-07-01107157110.3390/biomedicines10071571The Peptide/Antibody-Based Surface Decoration of Calcium Phosphate Nanoparticles Carrying siRNA Influences the p65 NF-κB Protein Expression in Inflamed Cells In VitroElena K. Müller0Nataniel Białas1Matthias Epple2Ingrid Hilger3Department of Experimental Radiology, Institute of Diagnostic and Interventional Radiology, Jena University Hospital, Friedrich Schiller University Jena, Am Klinikum 1, D-07740 Jena, GermanyInorganic Chemistry and Center for Nanointegration Duisburg-Essen (CENIDE), University of Duisburg-Essen, Universitaetsstrasse 5-7, D-45117 Essen, GermanyInorganic Chemistry and Center for Nanointegration Duisburg-Essen (CENIDE), University of Duisburg-Essen, Universitaetsstrasse 5-7, D-45117 Essen, GermanyDepartment of Experimental Radiology, Institute of Diagnostic and Interventional Radiology, Jena University Hospital, Friedrich Schiller University Jena, Am Klinikum 1, D-07740 Jena, GermanyEarlier studies with nanoparticles carrying siRNA were restricted to investigating the inhibition of target-specific protein expression, while almost ignoring effects related to the nanoparticle composition. Here, we demonstrate how the design and surface decoration of nanoparticles impact the p65 nuclear factor-kappa B (NF-κB) protein expression in inflamed leucocytes and endothelial cells in vitro. We prepared silica-coated calcium phosphate nanoparticles carrying encapsulated siRNA against p65 NF-κB and surface-decorated with peptides or antibodies. We show that RGD-decorated nanoparticles are efficient in down-regulating p65 NF-κB protein expression in endothelial cells as a result of an enhanced specific cellular binding and subsequent uptake of nanoparticles. In contrast, nanoparticles decorated with IgG (whether specific or not for CD69) are efficient in down-regulating p65 NF-κB protein expression in T-cells, but not in B-cells. Thus, an optimized nanoparticle decoration with xenogenic IgG may stimulate a specific cellular uptake. In summary, the composition of siRNA-loaded calcium phosphate nanoparticles can either weaken or stimulate p65 NF-κB protein expression in targeted inflamed leucocytes and endothelial cells. In general, unveiling such interactions may be very useful for the future design of anti-p65 siRNA-based nanomedicines for treatment of inflammation-associated diseases.https://www.mdpi.com/2227-9059/10/7/1571RGDsCD69IgGsintegrinsp65 NF-κBgene silencing
spellingShingle Elena K. Müller
Nataniel Białas
Matthias Epple
Ingrid Hilger
The Peptide/Antibody-Based Surface Decoration of Calcium Phosphate Nanoparticles Carrying siRNA Influences the p65 NF-κB Protein Expression in Inflamed Cells In Vitro
Biomedicines
RGDs
CD69
IgGs
integrins
p65 NF-κB
gene silencing
title The Peptide/Antibody-Based Surface Decoration of Calcium Phosphate Nanoparticles Carrying siRNA Influences the p65 NF-κB Protein Expression in Inflamed Cells In Vitro
title_full The Peptide/Antibody-Based Surface Decoration of Calcium Phosphate Nanoparticles Carrying siRNA Influences the p65 NF-κB Protein Expression in Inflamed Cells In Vitro
title_fullStr The Peptide/Antibody-Based Surface Decoration of Calcium Phosphate Nanoparticles Carrying siRNA Influences the p65 NF-κB Protein Expression in Inflamed Cells In Vitro
title_full_unstemmed The Peptide/Antibody-Based Surface Decoration of Calcium Phosphate Nanoparticles Carrying siRNA Influences the p65 NF-κB Protein Expression in Inflamed Cells In Vitro
title_short The Peptide/Antibody-Based Surface Decoration of Calcium Phosphate Nanoparticles Carrying siRNA Influences the p65 NF-κB Protein Expression in Inflamed Cells In Vitro
title_sort peptide antibody based surface decoration of calcium phosphate nanoparticles carrying sirna influences the p65 nf κb protein expression in inflamed cells in vitro
topic RGDs
CD69
IgGs
integrins
p65 NF-κB
gene silencing
url https://www.mdpi.com/2227-9059/10/7/1571
work_keys_str_mv AT elenakmuller thepeptideantibodybasedsurfacedecorationofcalciumphosphatenanoparticlescarryingsirnainfluencesthep65nfkbproteinexpressionininflamedcellsinvitro
AT natanielbiałas thepeptideantibodybasedsurfacedecorationofcalciumphosphatenanoparticlescarryingsirnainfluencesthep65nfkbproteinexpressionininflamedcellsinvitro
AT matthiasepple thepeptideantibodybasedsurfacedecorationofcalciumphosphatenanoparticlescarryingsirnainfluencesthep65nfkbproteinexpressionininflamedcellsinvitro
AT ingridhilger thepeptideantibodybasedsurfacedecorationofcalciumphosphatenanoparticlescarryingsirnainfluencesthep65nfkbproteinexpressionininflamedcellsinvitro
AT elenakmuller peptideantibodybasedsurfacedecorationofcalciumphosphatenanoparticlescarryingsirnainfluencesthep65nfkbproteinexpressionininflamedcellsinvitro
AT natanielbiałas peptideantibodybasedsurfacedecorationofcalciumphosphatenanoparticlescarryingsirnainfluencesthep65nfkbproteinexpressionininflamedcellsinvitro
AT matthiasepple peptideantibodybasedsurfacedecorationofcalciumphosphatenanoparticlescarryingsirnainfluencesthep65nfkbproteinexpressionininflamedcellsinvitro
AT ingridhilger peptideantibodybasedsurfacedecorationofcalciumphosphatenanoparticlescarryingsirnainfluencesthep65nfkbproteinexpressionininflamedcellsinvitro