Precisely Controlling the Activation of an Iron-Locked Drug Generator in the Liver Sinusoid to Enhance Barrier Penetration and Reduction of Liver Fibrosis.

Complex physical barriers and the nanomaterial's clearance mechanism in the liver greatly hinder the feasibility of using a conventional liver-targeting nanoplatform to deliver antifibrotic drugs to pathological sites for the treatment of liver fibrosis. Here, a novel drug delivery strategy was designed to overcome drug penetration barriers in a fibrotic liver and cooperated with oral nattokinase (NKase)-mediated antifibrosis therapy as a proof of concept, which relies on the coadministration of a nanosized iron-locked drug generator (named Pro-HAase) and orally absorbed iron chelator deferasirox (DFX). Such a strategy starts from the rapid accumulation of intravenously injected Pro-HAase in the microcapillaries of the fibrotic liver followed by disrupting the polyphenol-iron coordination inside Pro-HAase by DFX, liberating antifibrotic components, including procyanidine (PA) and hyaluronidase (HAase).

Integrating network pharmacology and experimental validation to decipher the pharmacological mechanism of DXXK in treating diabetic kidney injury.

Diabetes mellitus (DM) is a chronic metabolic disease that is highly susceptible to kidney injury. Di'ao XinXueKang capsules (DXXK) is a novel Chinese herbal medicine that has been used in clinical trials for the therapy of DM and kidney disease, but the underlying pharmacological mechanism remains unclear. This study aims to integrate network pharmacology, molecular docking and in vivo experiments to explore the potential mechanisms of DXXK in the treatment of diabetic kidney injury.

Breaking-Down Tumoral Physical Barrier by Remotely Unwrapping Metal-Polyphenol-Packaged Hyaluronidase for Optimizing Photothermal/Photodynamic Therapy-Induced Immune Response.

The therapy of solid tumors is often hindered by the compact and rigid tumoral extracellular matrix (TECM). Precise reduction of TECM by hyaluronidase (HAase) in combination with nanotechnology is promising for solid tumor therapeutics, yet remains an enormous challenge. Inspired by the treatment of iron poisoning, here a remotely unwrapping strategy is proposed of metal-polyphenol-packaged HAase (named PPFH) by sequentially injecting PPFH and a clinically used iron-chelator deferoxamine (DFO).

Drug in Therapeutic Polymer: Sinomenine-Loaded Oxidation-Responsive Polymeric Nanoparticles for Rheumatoid Arthritis Treatment.

Rheumatoid arthritis (RA) is a chronic inflammatory joint disease that frequently involves cartilage damage and the destruction of the bone structure, ultimately resulting in disability and long-term pain. It is clear that overexpression of reactive oxygen species (ROS) and the complex inflammatory microenvironment are the main causes of RA pathogenesis; thereby, the efficacy of any single-drug treatment is limited. Herein, we formulated a therapeutic hyaluronic acid derivative (PAM-HA) with adsorption capacity to the subchondral bone, a long retention time within inflamed joints, and ROS-scavenging capacity, which was used as a drug carrier for realizing the controlled release of sinomenine (Sin) within arthritic joints.