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PEG-Grafted Oligolysines Stabilize DNA Origami While Enhancing Receptor-Specific Cell Binding.
Mohammadamir G Moghadam1, Travis R Douglas1, Shana Alexander1
1Institute of Biomedical Engineering, University of Toronto, Toronto M5S 3E3, Canada.
Journal of the American Chemical Society
|July 21, 2025
Summary
New DNA nanostructure coatings enhance stability and cell binding for biomedical uses. These polyethylene glycol (PEG)-grafted oligolysine coatings improve DNA nanodevices, overcoming previous limitations.
Area of Science:
- Biotechnology
- Materials Science
- Nanotechnology
Background:
- DNA nanostructures (DNs) are promising for targeted biomedical applications but suffer from poor stability in physiological conditions.
- Existing protective coatings can enhance DN stability but often hinder ligand-receptor interactions, reducing efficacy.
- Developing stable and functional DNs requires balancing structural integrity with biological accessibility.
Purpose of the Study:
- To engineer novel protective coatings for DNA nanostructures that enhance stability while preserving receptor-specific cell binding.
- To explore the impact of coating parameters like lysine valency, PEG molecular weight, and grafting density on DN performance.
- To establish a design framework for creating robust, targeted DNA nanodevices.
Main Methods:
- Synthesis and screening of a 36-member library of polyethylene glycol (PEG)-grafted oligolysine coatings.
- Characterization of DN coating affinity and cargo stability using quantitative assays.
- Evaluation of antibody-functionalized coated DNs for Fcγ receptor engagement on dendritic cells (DC2.4).
- Application of statistical modeling to identify optimal multiparametric design combinations.
Main Results:
- Identified three PEG-grafted oligolysine formulations with ~6-fold higher DN binding affinity and ~30-fold greater cargo stability compared to K10-b-PEG5k.
- Demonstrated that antibody-functionalized coated DNs achieved a 12-fold increase in binding specificity to Fcγ receptors on DC2.4 cells.
- Statistical modeling confirmed that optimal performance relies on the coordinated optimization of multiple coating parameters.
Conclusions:
- Polyethylene glycol (PEG)-grafted oligolysine coatings offer a dual benefit of enhanced DNA nanostructure stability and preserved receptor-specific binding.
- These novel coatings significantly outperform traditional K10-b-PEG5k, addressing key limitations in DN applications.
- The findings provide a design framework for engineering advanced, biostable DNA nanodevices for diverse biological and therapeutic applications.
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