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Updated: Apr 25, 2026
10:38
Synthesis of Functionalized 10-nm Polymer-coated Gold Particles for Endothelium Targeting and Drug Delivery
Published on: January 15, 2018
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Nanoparticle multivalency counterbalances the ligand affinity loss upon PEGylation
Robert Hennig1, Klaus Pollinger1, Anika Veser1
1Department of Pharmaceutical Technology, University of Regensburg, Universitaetsstrasse 31, 93053 Regensburg, Germany.
Summary
Attaching ligands to nanoparticles can improve their cell interaction. However, polyethylene glycol (PEG) shielding can reduce ligand affinity, but nanoparticle multivalency restores potent receptor binding.
Area of Science:
- Biotechnology
- Nanomedicine
- Pharmacology
Background:
- Ligand conjugation to nanoparticles is key for targeted delivery.
- Polyethylene glycol (PEG) shielding can hinder ligand-receptor interactions.
- Understanding how PEGylation affects ligand affinity is crucial for nanoparticle design.
Purpose of the Study:
- To investigate the impact of PEGylation on ligand affinity.
- To evaluate the receptor binding of PEGylated nanoparticles.
- To quantify the multivalent effect on ligand-receptor interactions.
Main Methods:
- Investigated the affinity of a model ligand (EXP3174) before and after PEGylation.
- Assessed ligand affinity when attached to PEGylated nanoparticles.
- Measured receptor binding specificity and displacement assays.
Main Results:
- PEGylated ligand showed a 580-fold decrease in receptor affinity.
- Nanoparticles regained low nanomolar receptor affinity due to multivalency.
- One nanoparticle carried 11.2 ligands, enhancing binding by 22.5-fold.
- Targeted nanoparticles specifically bound the angiotensin II receptor type 1 (AT1R).
Conclusions:
- PEGylation significantly impairs small-molecule ligand receptor affinity.
- Nanoparticle multivalency compensates for reduced affinity, enhancing avidity.
- Affinity testing of ligands before and after PEGylation is recommended for potent nanoparticle targeting.
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