Phenolic Ligand–Metal Charge Transfer Induced Copper Nanozyme with Reactive Oxygen Species-Scavenging Ability for Chronic Wound Healing

Chronic wounds frequently arise as a complication in diabetic patients, and their management remains a significant clinical hurdle due to their nonhealing nature featured by heightened oxidative stress and impaired healing cells at the wound site. Herein, we present a 2D copper antioxidant nanozyme induced by phenolic ligand–metal charge transfer (LMCT) to eliminate reactive oxygen species (ROS) and facilitate the healing of chronic diabetic wounds. We found that polyphenol ligands coordinated on the Cu3(PO4)2 nanosheets led to a strong charge transfer at the interface and regulated the valence states of Cu. The obtained Cu nanozyme exhibited efficient scavenging ability toward different oxidative species and protected human cells from oxidative damage. The nanozyme enhanced the healing of diabetic wounds by promoting re-epithelialization, collagen deposition, angiogenesis, and immunoregulation. This work demonstrates the LMCT-induced ROS scavenging ability on a nanointerface, providing an alternative strategy of constructing metal-based nanozymes for the treatment of diabetic wounds as well as other diseases

Microencapsulation of Ionic Liquid by Interfacial Self-Assembly of Metal-Phenolic Network for Efficient Gastric Absorption of Oral Drug Delivery

Improving bioavailability of orally delivered drugs is still challenging, as conventional drug delivery systems suffer from non-specific drug delivery in the gastrointestinal (GI) tract and limited drug absorption efficiency. Gastric drug delivery is even more difficult due to the harsh microenvironment, short retention time, and physiologic barriers in the stomach. Here, an oral drug delivery microcapsule system was developed for gastric drug delivery, which consists of ionic liquid (IL) as the inner carrier and metal-phenolic network (MPN) as the microcapsule shell. The IL@MPN microcapsules are prepared by interfacial self-assembly of FeIII and quercetin at the interface of hydrophobic IL ([EMIM][NTf2]) and water. The formation of MPN shell could improve the stability of IL droplets in water and endow the system with pH-response drug release properties, while the encapsulated IL core could efficiently load the drug and enhance the drug tissue permeability. The IL@MPN microcapsules showed enhanced drug absorption in the stomach after oral administration in a rat model, where the microcapsules are disassembled in gastric acid, and the released IL could reduce the viscosity of mucus gel and increase the drug transport rate across endothelial cells. This work presents a simple yet efficient strategy for oral drug delivery to the stomach. Given the diversity and versatility of both MPN and IL, the proposed self-assembled microcapsules could expand the toolbox of drug delivery systems with enhanced oral drug bioavailability