Multifunctional hyaluronic acid-mediated quantum dots for targeted intracellular protein delivery and real-time fluorescence imaging

The use of multifunctional quantum dots (QDs) as smart nanocarriers has exhibited substantial promise for imaging, targeting and therapeutic functionalities. Here, we describe the synthesis of green-light emitting CdZnSeS/ZnS quantum dots (QDs) combined with redox-sensitive hyaluronic acid ligand (hyaluronic acid-disulfide-linked poly(ethylene glycol)-histamine-diethylenetriamine, HA-PEG(SS)-His-Diet) for the targeted intracellular delivery of protein drugs. The generation of HA-PEG(SS)-His-Diet-QD exhibits monodispersity with high quantum yield, negligible cytotoxicity and long-term stability at pH 7.4 and 5.5. These HA-PEG(SS)-His-Diet-QDs could effectively immobilize cytochrome C (CC) with high loading efficiency, enable target of CD44-overexpressing MCF-7 human breast tumor cells, and accelerate protein release under high intracellular glutathione concentration condition. The HA-PEG(SS)-His-Diet-QD act as a promising nanocarrier for enhanced endo/lysosomal escape, targeted delivery of proteins and real-time cellular imaging. In addition, CC-loaded-HA-PEG(SS)-His-Diet-QD could effectively induce the CD44-positive cancer cells apoptosis in vitro. Ultimately, this redox-sensitive and fluorescent QD-based nanocarrier has shown major promise for targeted intracellular protein transport.