Hyaluronic acid-coated single-walled carbon nanotubes loaded with doxorubicin for the treatment of breast cancer.

Hyaluronic acid (HA)-modified amino single-walled carbon nanotubes (NH₂-SWCNTs) were developed for targeted delivery of doxorubicin (DOX) to improve breast cancer treatment. HA, which specifically binds to the CD44 receptor, was non-covalently coated on NH₂-SWCNTs through simply electrostatic adsorption. The formed SWCNTs-DOX-HA complexes were characterized in terms of morphology, particle size and zeta potential by different techniques. The DOX loading percentage on the SWCNTs-DOX-HA complexes was 81.5±1.0 %. In vitro release study showed that the release of DOX was pH-triggered and was faster at a lower pH 5.5 (tumor cell microenvironment) than that under physiological conditions (pH 7.4), which was beneficial for intracellular drug release. The SWCNTs-DOX-HA showed a significantly improved intracellular delivery of DOX in CD44 overexpressing MDA-MB-231 cells by flow cytometry and confocal microscopy. Of particular importance, the SWCNTs-DOX-HA complexes were better than the unmodified SWCNTs-DOX on inhibiting proliferation and inducing apoptosis of cells. In addition, the migration of MDA-MB-231 cells was significantly blocked by SWCNTs-DOX-HA. In the cancer cell spheroids assay, SWCNTs-DOX-HA exhibited notable effect to inhibit the growth of cancer cell spheroids. All these results indicated that this developed SWCNTs-DOX-HA complexes hold a great promise to be used as an efficient nano-sized anticancer drug formulation for tumor-targeted treatment.