Engineering Stability-Tunable DNA Micelles Using Photocontrollable Dissociation of an Intermolecular G-Quadruplex

Because of their facile preparation, small size (<100 nm), programmable design, and biocompatibility, lipid-based DNA micelles show enormous potential as a tool to monitor biological events and treat,human diseases. However, their structural stability in biological matrices suffers from spatiotemporal variability, thus limiting their in vivo use. Herein, we have engineered stability-tunable DNA micelle flares using photocontrollable dissociation of intermolecular G-quadruplexes, which confers DNA micelle flares with robust structural stability against disruption by serum albumin. However, once exposed to light, the G-quadruplex formation is blocked by strand hybridization, resulting in the loss of stability in the presence of serum albumin and subsequent cellular uptake. This programmable regulation to stabilize lipid-based micelles in the presence of fatty-acid-binding serum albumin should further the development of biocompatible DNA micelles for in vivo applications.