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Engineering Hetero-Layered Mannodendrimers to Enhance Macrophage Receptor Binding
Mukul Raj Gupta1, Alain Zgheib2, Bogdan Alexandru Danalache2
1Glycosciences and Nanomaterial Laboratory, Département de Chimie, Université du Québec à Montréal, P.O. Box 8888, Succ. Centre-Ville, Montréal, Québec H3C 3P8, Canada.
Biomacromolecules
|October 28, 2025
Summary
Mannosylated dendrimers show high affinity for macrophage mannose receptors (MMRs), making them promising for targeted immunotherapy. These nanoparticles offer a novel platform for drug and vaccine delivery.
Area of Science:
- Immunology
- Nanotechnology
- Biochemistry
Background:
- Cell surface carbohydrate-binding proteins, including mannose receptors (MRs), are crucial for immune surveillance.
- Macrophage mannose receptors (MMRs) are particularly attractive targets for developing targeted therapies.
- Existing delivery systems can be improved for enhanced specificity and efficacy.
Purpose of the Study:
- To synthesize and characterize a library of heterolayered mannosylated dendrimers.
- To evaluate the selective affinity of these dendrimers for MMRs.
- To explore the potential of glycodendrimers as platforms for targeted immunotherapy.
Main Methods:
- Synthesis of di- to hexavalent scaffolds using click chemistry.
- Conjugation of scaffolds to dendrons with α-d-mannopyranoside moieties.
- Assessment of cellular uptake using Nile Red-labeled liposomes and silencing of MRC1/CD206.
- Competitive inhibition assays to determine binding affinity (IC50).
Main Results:
- A 12-valent mannodendrimer nanoparticle (∼2.5 nm) exhibited the highest affinity for MMRs (IC50 = 28.9 ± 0.2 μM).
- The uptake of mannosylated liposomes was dependent on MRC1/CD206 expression.
- Dendrimer nanoparticles demonstrated superior affinity compared to larger liposomal constructs.
Conclusions:
- Glycodendrimers represent an effective platform for targeted immunotherapy.
- Nanoscale geometry and precise ligand presentation are critical for optimizing MMR targeting.
- These findings pave the way for advanced drug and vaccine delivery systems.

