Supercritical fluid-assisted fabrication of diselenide-bridged polymeric composites for improved indocyanine green-guided photodynamic therapy

Abstract In recent years, the stimuli-responsive delivery of drugs based on diselenide-bridged polymeric nanocomposites have gathered significant attention from researchers towards augmented anticancer therapy, owing to the unique dual reactive oxygen species (ROS) as well as glutathione (GSH) redox-responsive diselenide bonds. Despite their success in delivery of diverse therapeutics, the fabrication of such diselenide-bridged polymeric nanocomposites with high performance efficiency is often limited due to the relatively high sensitivity of diselenide bonds to various stimuli such as light, temperature, and both oxidation and reduction. In an attempt to address these attributes, herein, we demonstrate the fabrication of indocyanine green (ICG)-loaded diselenide-containing polymeric nanoparticles using the supercritical fluid (SCF)-assisted rapid and facile synthesis approach for ROS/GSH-responsive drug delivery platform towards augmented anticancer therapy. Initially, the diselenide-containing poly (ethylene glycol)-poly(e-caprolactone)-poly(ethylene glycol) block copolymers (PSe) are synthesized based on stannous octoate initiated ring-opening polymerization and subsequent esterification with carboxylic acid-functionalized polyethylene glycol (PEG-COOH). Further, the ICG molecules are loaded into the copolymer nanocomposites via the incorporation of coprecipitation interactions between PSe and ICG through the convenient and highly effective SCF technology. These nanocomposites afforded high drug loading (up to 48.5%) and encapsulation efficiency (up to 85.1%), along with uniform distribution and desired photo-stability. Finally, various photodynamic therapy (PDT)-related experiments both in vitro and in vivo have shown that the fabricated ROS-responsive drug delivery system based on ICG and PSe is capable of devastating tumor cells.