ATP/Hyals dually responsive core-shell hyaluronan/chitosan-based drug nanocarrier for potential application in breast cancer therapy

The stability of self-assembled drug nanocarriers during blood circulation and the controlled intracellular drug delivery are two challenges in cancer therapy. In this paper, we constructed an adenosine triphosphate (ATP)/hyaluronidase(Hyals) dually responsive core-shell hyaluronan/chitosan-based drug nanocarrier for breast cancer therapy, using SNX-loaded 3-fluoro-4-carboxyphenylboronic acid-conjugated quaternary ammonium chitosan nanoparticles ([email protected] NPs) as the core and crosslinked polyethylene glycol-/methacrylate-modified hyaluronic acid (mHA-PEG) as the shell. The formed [email protected]/mHA-PEG NPs were stable against salt ion strength, pH values and human plasma mimicking the bloodstream, but ATP/Hyals dually sensitive with a drug delivery of 85% within 48 h in the mimicking intracellular environment of breast cancer cells. These nanoparticles showed a low hemolysis of less than 3%, a high resistance to bovine serum albumin adsorption of 0.06 mg/mg, and an efficient internalization by two breast cancer cell lines (MCF-7 and MDA-MB-453). The cell culture indicated that they were friendly to human skin fibroblasts, but presented a close IC50 value to SNX for MCF-7 (0.14 μg mL−1) and MDA-MB-453 (0.05 μg mL−1) at 48 h, respectively. Thus, [email protected]/mHA-PEG NPs were potential drug nanocarriers for breast tumor therapy.