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

Abstract

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.

Metal-phenolic networks as tuneable spore coat mimetics

“…Under acidic conditions, hydroxyl groups on the polyphenols in the MPN complexes are protonated, disrupting chelation and leading to disassembly. 34 For oral delivery applications, this pH-dependent degradation is important, as it provides an inherent on-demand disassembly for the cells upon their exposure to stomach acid and intestinal fluid. Though uncoated B. subtilis demonstrated faster recovery than MPN-coated cells post-reconstitution in nutrient broth with PBT or PCT (Fig.…”

Protection of Anaerobic Microbes from Processing Stressors Using Metal–Phenolic Networks

“…MPNs are pH-sensitive and readily degrade upon treatment with a mild acid (conditions similar to stomach acid), enabling their “on demand” dissolution . Immediately following the addition of acid, the color of the cell suspension changed to white, indicating removal of the MPN shell.…”

“…MPNs are pH-sensitive and readily degrade upon treatment with a mild acid (conditions similar to stomach acid), enabling their "on demand" dissolution. 35 Immediately following the addition of acid, the color of the cell suspension changed to white, indicating removal of the MPN shell. After 1 h of incubation in 10 mM HCl, the log(CFU/mL) value for coated E. coli increased to 7.26 ± 1.07, and the delay in exponential growth (t eg ) decreased to 8 h, similar to that of uncoated cells (Figure 3b).…”

Hyaluronic Acid Nanoparticles as Nanomedicine for Treatment of Inflammatory Diseases

“…The drug-loaded HA-NPs can selectively and effectively accumulate into disease sites via the EPR effect or CD44 receptor-mediated endocytosis. Shin et al reported the metal-phenolic network-coated HA-NPs to facilitate drug release in tumor microenvironments [ 119 ]. It was confirmed that the DOX release rate was high in the mildly acidic condition, mimicking the tumor microenvironment.…”