Highly stable hybrid single-micelle: A universal nanocarrier for hydrophobic bioimaging agents

As the first-line technology, micelles play a pivotal role in in vivo delivery of theranostic agents because of their high biocompatibility and universality. However, in complex physiological environments (extreme dilution, pH, and oxidation or reduction, etc.), they generally suffer from structural instability and insufficient protection for encapsulated cargos. It is urgent to reinforce the structural stability of the micelles at the single-micelle level. By using the FDA-approved Pluronic F127 surfactants and indocyanine green (ICG) bioimaging agents as model, herein, we propose the silane-crosslinking assisted strategy to reinforce the structural stability of the single-micelle. Different from the traditional silane hydrolysis under the harsh experimental conditions (acidic, alkaline, and high temperature hydrothermal, etc.), the ICG loaded F127@SiO₂ hybrid single-micelles (ICG@H-micelles) with controllable sizes (15–35 nm) are synthesized at neutral pH and room temperature, which is crucial for the maintenance of the physicochemical properties of the encapsulated cargos. With the ultra-thin SiO₂ (< 5 nm) at hydrophilic layer of the single-micelle, the structural and fluorescence stability of ICG@H-micelles are much higher than the conventional micelle (ICG@micelles) in the simulated physiological environments of dilution, oxidation or reduction, and low pH. Because of the high structural and fluorescence stability, the ICG@H-micelles also exhibit longer duration time in the tumor and gastrointestinal tract bioimaging.