Determinants of Ligand-Functionalized DNA Nanostructure-Cell Interactions.

Area of Science:

• Biotechnology
• Nanotechnology
• Molecular Biology

Background:

• Ligand-functionalized nanomaterials are crucial for targeted nanomedicines.
• DNA nanotechnology enables precise construction of nanostructures for controlled ligand incorporation.
• Understanding cellular accessibility is key for effective targeting of cell surface receptors.

Purpose of the Study:

• To investigate design parameters influencing antibody-functionalized DNA nanostructures' binding to cell surface receptors.
• To identify structural determinants that modulate receptor accessibility and binding efficiency.
• To establish design rules for optimizing cellular targeting with DNA nanostructures.

Main Methods:

• Systematic investigation of antibody-functionalized DNA nanostructures.
• Evaluation of binding to specific receptors: programmed cell death protein 1 (PD-1), epidermal growth factor receptor (EGFR), and human epidermal growth factor receptor 2 (HER2).
• Analysis of nanostructure size and DNA handle location as key design parameters.

Main Results:

• The native antibody affinity remains unchanged, but overall receptor binding is reduced compared to soluble antibodies due to accessibility limitations.
• Nanostructure size and the location of DNA handles critically govern receptor binding efficiency.
• Insights into receptor binding mechanisms were gained, highlighting the impact of nanostructure architecture.

Conclusions:

• Antibody-functionalized DNA nanostructures can bind cell surface receptors, but efficiency is influenced by accessibility.
• Nanostructure size and DNA handle placement are critical design factors for optimizing cellular targeting.
• This study provides essential design rules for developing effective ligand-functionalized DNA nanostructures for nanomedicine.