Mannose-Based Molecular Patterns on Stealth Microspheres for Receptor-Specific Targeting of Human Antigen-Presenting Cells
Abstract
The targeting of antigen-presenting cells has recently gained strong attention for both targeted vaccine delivery and immunomodulation. We prepared surface-modified stealth microspheres that display various mannose-based ligands at graded ligand densities to target phagocytic C-type lectin receptors (CLRs) on human dendritic cells (DCs) and macrophages. Decoration of microspheres with carbohydrate ligands was achieved (i) by electrostatic surface assembly of mannan onto previously formed adlayers of poly( l-lysine) (PLL) or a mix of PLL and poly( l-lysine)- graft-poly(ethylene glycol) (PLL-PEG), or (ii) through assembly of PLL-PEG equipped with small substructure mannoside ligands, such as mono- and trimannose, as terminal substitution of the PEG chains. Microspheres carrying mannoside ligands were also studied in combination with an integrin-targeting RGD peptide ligand. Because of the presence of a mannan or PEG corona, such microspheres were protected against protein adsorption and opsonization, thus allowing the formation of specific ligand-receptor interactions. Mannoside density was the major factor for the phagocytosis of mannoside-decorated microspheres, although with limited efficiency. This strengthens the recent hypothesis by other authors that the mannose receptor (MR) only acts as a phagocytic receptor when in conjunction with yet unidentified partner receptor(s). Analysis of DC surface markers for maturation revealed that neither surface-assembled mannan nor mannoside-modified surfaces on the microspheres could stimulate DC maturation. Thus, phagocytosis upon recognition by CLRs alone cannot trigger DC activation toward a T helper response. The microparticulate platform established in this work represents a promising tool for systematic investigations of specific ligand-receptor interactions upon phagocytosis, including the screening for potential ligands and ligand combinations in the context of vaccine delivery and immunomodulation.
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Mannan or PEG coating protects against protein opsonization, enabling specific receptor-ligand binding.
“Mannan or PEG coating was shown to protect against protein opsonization, enabling specific receptor-ligand binding.”
From Use of lectin-functionalized particles for oral immunotherapy (2012) · cites this paper as [72]
Mannose coupling to microspheres initiated phagocytosis by C-type lectin receptor but could not stimulate DC maturation and activation toward T-cell responses.
“However, mannose coupling to microspheres initiated the phagocytosis by C-type lectin receptor, it could not stimulate DC maturation and activation toward T-cell responses [72].”
From Use of lectin-functionalized particles for oral immunotherapy (2012) · cites this paper as [72]
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- Authors
- Wattendorf, U., Coullerez, G., Vörös, J., Textor, M., & Merkle, H. P.
- Affiliations
- ETH Zurich (CH)
- Institute for Pharmaceutical Sciences, ETH Zurich, 8093 Zurich, Switzerland, Laboratory for Surface Science and Technology, ETH Zurich, 8093 Zurich, Switzerland, and Laboratory for Biosensors and Bioelectronics, ETH Zurich, 8092 Zurich, Switzerland
- Corresponding author
- Merkle, Hans P.
- ORCID
- Textor, Marcus
- Venue
- Langmuir
- Publisher
- American Chemical Society (ACS)
- Published
- 2008-09-12
- Volume
- 24
- Issue
- 20
- Pages
- 11790-11802
- ISSN
- 0743-7463 (ISSN-L)
- 1520-5827
- OpenAlex
- W1986437885
- Cited by
- 58
- References
- 48
- Citations by year
- 2025: 1 · 2024: 1 · 2023: 2 · 2022: 3 · 2020: 2 · 2019: 3 · 2018: 2 · 2017: 1 · 2016: 3 · 2015: 2 · 2014: 7 · 2013: 9 · 2012: 4
- FWCI
- 2.36
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Langmuir (publishedVersion)
- PubMed (publishedVersion)
- Zurich Open Repository and Archive (University of Zurich) (submittedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
- Keywords
- CD206, C-type lectin receptors, dendritic cells, macrophages, antigen-presenting cells, mannan, RGD peptide, integrin targeting, phagocytosis, DC maturation, vaccine delivery, immunomodulation, ligand-receptor interactions, protein adsorption resistance, opsonization
- MeSH terms
- Animals, Antigen-Presenting Cells, Carbohydrates, Cattle, Dendritic Cells, Humans, Hydrogen-Ion Concentration, Mannosides, Microspheres, Monocytes, Phagocytosis, Polyethylene Glycols, Polylysine, Serum Albumin, Static Electricity
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