Biotin-modified hyaluronic acid double-target nanoparticles for quercetin and IR780 delivery: Fabrication, characterization, and biological properties

Currently, the use of nanotechnology to repurpose traditional drugs has emerged as a promising strategy for cancer treatment. Quercetin (Qu), a chemotherapy molecule, has excellent antitumor activity, and IR780, a photosensitizer, possesses sound tumor phototherapy effects. However, both compounds have poor water solubility and other drawbacks that hinder their extensive clinical applications. To effectively utilize two molecules in the fight against cancer, a new multifunctional chemical-phototherapy nanoplatform with tumor target and glutathione (GSH) response was designed. By modifying hyaluronic acid (HA), the amphiphilic molecule carrying biotin and IR780 was obtained, which self-assembled to load the antitumor active molecule Qu, namely Qu@BHSI. In addition to addressing the hydrophobic issue of Qu and IR780, the prepared nanoparticles can rapidly release Qu with high concentrations of GSH present and generate heat and cytotoxic reactive oxygen species (ROS) under near-infrared light. The biological function research showed that Qu@BHSI nanoparticles had the ability to suppress the growth of A549 cells, induce cell apoptosis, stimulate ROS production in zebrafish, and inhibit angiogenesis in transgenic zebrafish. The construction of nanosystems provides new or alternative strategies and approaches for effectively repurposing classical drug molecules including photosensitizers and chemotherapy drugs.