Design of Diselenide-Bridged Hyaluronic Acid Nano-antioxidant for Efficient ROS Scavenging to Relieve Colitis

Abstract

Overproduction of reactive oxygen species (ROS), a key characteristic of inflammatory bowel disease (IBD), is responsible for dysregulation of signal transduction, inflammatory response, and DNA damage, which ultimately leads to disease progression and deterioration. Thus, ROS scavenging has become a promising strategy to navigate IBD. Inspired by the targeting capability of hyaluronic acid (HA) to CD44-overexpressed inflammatory cells together with the redox regulation capacity of diselenide compounds, we developed an oral nanoformulation, i.e., diselenide-bridged hyaluronic acid nanogel (SeNG), with a view to treat colitis through a ROS scavenging mechanism. Our data demonstrated that SeNG specifically accumulated in colitis tissue that was mediated by highly efficient CD44–HA interaction. This has allowed us to demonstrate a significant anti-inflammatory effect in an acute colitis mouse model induced by dextran sulfate sodium and trinitrobenzenesulfonic acid. Mechanistically, we continued to show SeNG reduced the ROS level via both direct elimination and up-regulation of the Nrf2/HO-1 signal pathway. Collectively, our work provides proof-of-principle evidence for a SeNG-mediated nano-antioxidant strategy, by which colitis could be effectively managed.

In-Tumor Biosynthetic Construction of Upconversion Nanomachines for Precise Near-Infrared Phototherapy

“…The green fluorescence signal was detected in MCF-7 cells after 2 h incubation, and the intensity continued to increase as the incubation time extended (Figure S6). Compared with UCNM, brighter intracellular green fluorescence in UCNM@HA was observed since HA could specifically recognize the tumor-overexpressed receptors (CD44) − (Figure A,B, and S7). Afterward, we studied 5-ALA-induced PpIX production in the cells.…”

1,2-Bis(2-aminophenoxy)ethane-N,N,N′,N′-tetraacetic Acid Acetoxymethyl Ester Loaded Reactive Oxygen Species Responsive Hyaluronic Acid–Bilirubin Nanoparticles for Acute Kidney Injury Therapy via Alleviating Calcium Overload Mediated Endoplasmic Reticulum Stress

“…during systemic circulation, resulting in the disassembly of the NPs. Most importantly, its hydrophilicity limits its use as a drug carrier for the delivery of hydrophobic drugs . Another promising strategy that has sparked widespread concern is grafting hydrophobic parts to the active group of HA to form an amphiphilic conjugate.…”

“…Most importantly, its hydrophilicity limits its use as a drug carrier for the delivery of hydrophobic drugs. 35 Another promising strategy that has sparked widespread concern is grafting hydrophobic parts to the active group of HA to form an amphiphilic conjugate. Thus, we chemically modified the HA backbone to increase its local hydrophobicity by Br, yielding a HA−Br conjugate for the construction of a drug delivery system capable of delivering the hydrophobic small molecule BAPTA-AM.…”

Cholesterol suppresses human iTreg differentiation and nTreg function through mitochondria-related mechanisms

“…What’s more, nanoantioxidants provide the possibility of targeted and temporally controlled delivery of antioxidants at specific body sites, which is especially suitable for AS treatment [ 45 , 46 ]. Even more interesting is that some NPs showed both ROS-scavenging and anti-inflammatory capacities themselves [ 47 ]. We believe that nano-MT may have a better AS-curing effect than common antioxidants and deserve further study.…”