Targeted Drug Delivery Systems Utilizing Mannose-Functionalized Nanoparticles

Targeted drug delivery systems employing mannose-functionalized nanoparticles harness the natural affinity between mannose ligands and specific cellular receptors to achieve selective uptake. By decorating nanoscale carriers—such as polymeric particles, liposomes or dendrimers—with mannose residues, these systems exploit endocytic pathways mediated by mannose receptors (CD206) on macrophages, dendritic cells and certain tumour cells. This strategy enhances therapeutic index by concentrating cytotoxic or immunomodulatory agents at the site of interest while reducing systemic exposure and off-target effects. The design of mannose-functionalized platforms involves careful control of particle size, surface charge and ligand density to optimise circulation time, biodistribution and receptor binding avidity. Stimuli-responsive elements—pH-sensitive linkers, redox-sensitive bonds or temperature-responsive polymers—may be incorporated to trigger drug release in intracellular compartments. Applications range from cancer chemotherapy and immunotherapy to treatment of infectious diseases and central nervous system disorders. Recent advances have focused on refining ligand architecture for maximal receptor engagement, elucidating intracellular trafficking pathways and demonstrating in vivo efficacy in preclinical models.

Research from Nature Portfolio

No recent Nature Portfolio content available.

Research from all publishers

Recent studies have elucidated structural requirements of mannose ligands and their multivalent presentation for efficient receptor binding. Work in 2024 detailed the synthesis of branched and linear oligomannosides on diverse templates—peptides, polymers and dendrimers—and demonstrated that optimal spacing and branching markedly enhance uptake by macrophages and dendritic cells. Another investigation explored carbohydrate-functionalized polymeric nanoparticles that modulate macrophage M1/M2 polarization. By conjugating mannose onto biodegradable polymer carriers, researchers achieved selective delivery of anti-inflammatory or pro-inflammatory agents to shift macrophage phenotype, offering potential in cancer immunotherapy and infectious-disease treatment. A third line of enquiry centred on mannosylated glycoliposomes formed from novel neoglycolipids. These self-assembled vesicles exhibited controlled size distribution, haemocompatibility and efficient cross-linking with lectins. In vitro and ex vivo assays confirmed enhanced cytosolic delivery of peptide therapeutics and improved plasma stability, highlighting promise for both systemic and intranasal administration to the central nervous system.

Targeted Drug Delivery Systems Utilizing Mannose-Functionalized Nanoparticles publication trend

The graph below shows the total number of articles in targeted drug delivery systems utilizing mannose-functionalized nanoparticles across all publications each year (not limited to Nature Index journals).

Technical terms

Nanoparticle: A particulate carrier with dimensions in the 1–1000 nm range designed to encapsulate or bind therapeutic agents for controlled delivery.

Mannose receptor: A C-type lectin (CD206) primarily expressed on macrophages and dendritic cells that mediates endocytosis of mannose-bearing ligands.

Glycoliposome: A liposomal vesicle whose surface is functionalized with glycolipids, combining lipid bilayer carriers with saccharide ligands for targeted delivery.

Multivalency: The presentation of multiple copies of a ligand on a single carrier surface to enhance binding strength (avidity) through simultaneous interactions with clustered receptors.

Endocytosis: The cellular process by which extracellular materials are internalized within vesicles, enabling nanoparticle uptake and intracellular drug release.

Macrophage polarization: The dynamic differentiation of macrophages into pro-inflammatory (M1) or anti-inflammatory (M2) phenotypes in response to microenvironmental cues.

References

1. Mannose Ligands for Mannose Receptor Targeting. International Journal of Molecular Sciences (2024).
2. Modulation of Macrophages M1/M2 Polarization Using Carbohydrate-Functionalized Polymeric Nanoparticles. Polymers (2020).
3. Synthesis & Evaluation of Novel Mannosylated Neoglycolipids for Liposomal Delivery System Applications. Pharmaceutics (2022).