Hyaluronic acid-functionalized halloysite nanotubes for targeted drug delivery to CD44-overexpressing cancer cells

Chemotherapeutic drug has inevitable drawbacks of nonspecific tumor targeting and poor therapeutic efficiency, limiting practical clinical applications. To overcome these challenges, a novel halloysite nanotube-based drug delivery system was designed for efficient CD44-mediated targeting in this study. CD44 molecule, a major receptor for hyaluronic acid (HA), overexpressed in aggressive cancer cells. The successful synthesis of hyaluronic acid modified halloysite (HNTs-NH-HA) complexes were proved by 13 C solid state NMR spectroscopy , FT-IR, XPS and TGA. Thereafter, a model anticancer drug doxorubicin (DOX) was loaded into HNTs-NH-HA to from the final drug delivery system (HNTs-NH-HA/DOX). In vitro cytotoxicity assay tests revealed that HNTs-NH-HA/DOX improved therapeutic efficacy of DOX by specific targeting. Furthermore, confocal laser scanning microscopy (CLSM) results showed better uptake of HNTs-NH-HA/DOX nanoparticles in CD44 receptor-positive cells than in CD44 receptor-negative cells. It was expected that HNTs-NH-HA drug delivery systems hold great potential for targeting CD44 over-expressing tumors.