PEGylated nanoparticles interact with macrophages independently of immune response factors and trigger a non-phagocytic, low-inflammatory response

PEGylated nanoparticles interact with macrophages independently of immune response factors and trigger a non-phagocytic, low-inflammatory response

Poly-ethylene-glycol (PEG)-based nanoparticles (NPs) - including cylindrical micelles (CNPs), spherical micelles (SNPs), and PEGylated liposomes (PLs) - are hypothesized to be cleared in vivo by opsonization followed by liver macrophage phagocytosis. This hypothesis has been used to explain the rapi...

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Bibliographic Details
Published in:Journal of controlled release Vol. 366; pp. 282 - 296
Main Authors: Asoudeh, Monireh, Nguyen, Nicole, Raith, Mitch, Denman, Desiree S., Anozie, Uche C., Mokhtarnejad, Mahshid, Khomami, Bamin, Skotty, Kaitlyn M., Isaac, Sami, Gebhart, Taylor, Vaigneur, Lauren, Gelgie, Aga, Dego, Oudessa Kerro, Freeman, Trevor, Beever, Jon, Dalhaimer, Paul
Format: Journal Article
Language:English
Published: Netherlands Elsevier B.V 01-02-2024
Subjects:
Animals
Autophagy
Endothelial Cells
Humans
Immunologic Factors
Inflammation
Lipopolysaccharides
Lipoprotein
Lipoproteins
Liposome
Macrophage
Macrophages
Mammals
Mice
Micelles
PEG
Phagocytosis
NP
CNP
DLS
Lipoprotein
BMDM
Autophagy
FPKM
LPS
LNP
TPM
BSA
DMEM
HDL
PRR
PBD
SNP
LDL
FBS
VLDL
P-S
oxLDL
KEGG
PAMPs
TLR
LIMP-2
NSG
DSPE
Liposome
HPLM
Inflammation
PCA
MARCO
PEG
PC
γG
SR-A
NIR
ROS
PEO
PL
Phagocytosis
Macrophage
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Summary:Poly-ethylene-glycol (PEG)-based nanoparticles (NPs) - including cylindrical micelles (CNPs), spherical micelles (SNPs), and PEGylated liposomes (PLs) - are hypothesized to be cleared in vivo by opsonization followed by liver macrophage phagocytosis. This hypothesis has been used to explain the rapid and significant localization of NPs to the liver after administration into the mammalian vasculature. Here, we show that the opsonization-phagocytosis nexus is not the major factor driving PEG-NP – macrophage interactions. First, mouse and human blood proteins had insignificant affinity for PEG-NPs. Second, PEG-NPs bound macrophages in the absence of serum proteins. Third, lipoproteins blocked PEG-NP binding to macrophages. Because of these findings, we tested the postulate that PEG-NPs bind (apo)lipoprotein receptors. Indeed, PEG-NPs triggered an in vitro macrophage transcription program that was similar to that triggered by lipoproteins and different from that triggered by lipopolysaccharide (LPS) and group A Streptococcus. Unlike LPS and pathogens, PLs did not increase transcripts involved in phagocytosis or inflammation. High-density lipoprotein (HDL) and SNPs triggered remarkably similar mouse bone-marrow-derived macrophage transcription programs. Unlike opsonized pathogens, CNPs, SNPs, and PLs lowered macrophage autophagosome levels and either reduced or did not increase the secretion of key macrophage pro-inflammatory cytokines and chemokines. Thus, the sequential opsonization and phagocytosis process is likely a minor aspect of PEG-NP – macrophage interactions. Instead, PEG-NP interactions with (apo)lipoprotein and scavenger receptors appear to be a strong driving force for PEG-NP – macrophage binding, entry, and downstream effects. We hypothesize that the high presence of these receptors on liver macrophages and on liver sinusoidal endothelial cells is the reason PEG-NPs localize rapidly and strongly to the liver. [Display omitted]
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ISSN:0168-3659
1873-4995
DOI:10.1016/j.jconrel.2023.12.019