Functional Polarization of Liver Macrophages by Glyco Gold Nanoparticles
Author
Other authors
Publication date
2025-04-24ISSN
2198-3844
Abstract
Macrophages are crucial drivers of innate immunity. Reprogramming macrophages to a restorative phenotype in cancer or autoimmune diseases can stop their cancer-promoting activity or trigger anti-inflammatory immunity. Glycans have emerged as key components for immunity as they are involved in many pathophysiological disorders. Previous studies have demonstrated that supraphysiological amounts of mannose (Man) or sialic acid (Sia) can inhibit tumor growth and stimulate differentiation of regulatory T cells. Man is known to affect glucose metabolism in glycolysis by competing for the same intracellular transporters and affecting macrophage polarization, whereas Sia alters macrophage differentiation via signaling through Siglec-1. Herein, this work describes a macrophage targeting platform using gold nanoparticles (GNPs) functionalized with Man and Sia monosaccharides which exhibit high liver tropism. A single dose of glyco-GNPs can convert macrophages to a restorative phenotype in two completely different immune environments. Man promotes tumor-associated macrophages toward an antitumorigenic activity in a MC38 liver colorectal cancer model by secretion of TNF-α, IL -1β, and IL -6 in the tumor microenvironment. However, in a proinflammatory environment, as observed in a mouse model of autoimmune disease, primary biliary cholangitis, Man impairs the production of TNF-α, IL-1β, Arg1, and IL-6 cytokines. The results probe the dual role of Man in macrophage repolarization in response to the immune system. This study is a proof-of-concept that demonstrates that nanomedicine using specific glycans designed to target other immune cells such as myeloid cells, are a promising strategy not only against cancer but also against other pathologies such as autoimmune diseases.
Document Type
Article
Document version
Published version
Language
English
Subject (CDU)
54 - Chemistry. Crystallography. Mineralogy
615 - Pharmacology. Therapeutics. Toxicology
616 - Pathology. Clinical medicine
Keywords
Glycans
Gold nanoparticles
Hepatic metastases
Immunotherapy
Primary biliary cholangitis
Polisacàrids
Nanopartícules
Metàstasi hepàtica
Immunoteràpia
Colangitis biliar primària
Pages
p.21
Publisher
Wiley
Is part of
Advanced Science 2025, 12 (16)
Grant agreement number
info:eu-repo/grantAgreement/EC/H2020/Marie Skłodowska-Curie/814236
This item appears in the following Collection(s)
Rights
© L'autor/a
Except where otherwise noted, this item's license is described as http://creativecommons.org/licenses/by/4.0/