DNA Nanocage-Based Artificial Receptor Generator for Hydrophobic Interaction-Based Specific Membrane Anchoring

Membrane receptor recognition is a specific biotargeting strategy for disease diagnosis and treatment, but it suffers from insufficient receptor expression levels. Hydrophobic interaction-based membrane anchoring strategy allows high anchoring density, but it lacks specificity. In this study, we present a DNA nanocage-based artificial receptor generator (DNARG) that combines the advantages of high specificity of receptor recognition and high density of hydrophobic membrane anchoring. DNARG can respond to environmental signals and generate amphiphilic nucleic acid-based artificial receptors through a segregation-activation mechanism. The generated artificial receptors can selectively anchor on target cell membranes through hydrophobic interaction and function as stable biotargets like natural protein receptors. We show that the density of artificial receptors on the target cell membrane is significantly higher than that of highly expressed natural receptors, resulting in significantly enhanced photodynamic therapy. Finally, we demonstrate that the artificial receptors generated by DNARG can work integrated with protein receptors to facilitate logic operations on the cell surface and precision therapy based on multiplex receptor analysis.