Metal-Phenolic Network-Coated Hyaluronic Acid Nanoparticles for pH-Responsive Drug Delivery

Although self-assembled nanoparticles (SNPs) have been used extensively for targeted drug delivery, their clinical applications have been limited since most of the drugs are released into the blood before they reach their target site. In this study, metal-phenolic network (MPN)-coated SNPs (MPN-SNPs), which consist of an amphiphilic hyaluronic acid derivative, were prepared to be a pH-responsive nanocarrier to facilitate drug release in tumor microenvironments (TME). Due to their amphiphilic nature, SNPs were capable of encapsulating doxorubicin (DOX), chosen as the model anticancer drug. Tannic acid and FeCl₃ were added to the surface of the DOX-SNPs, which allowed them to be readily coated with MPNs as the diffusion barrier. The pH-sensitive MPN corona allowed for a rapid release of DOX and effective cellular SNP uptake in the mildly acidic condition (pH 6.5) mimicking TME, to which the hyaluronic acid was exposed to facilitate receptor-mediated endocytosis. The DOX-loaded MPN-SNPs exhibited a higher cytotoxicity for the cancer cells, suggesting their potential use as a drug carrier in targeted cancer therapy.