Recent Studies on Hydrogels Based on H2O2-Responsive Moieties: Mechanism, Preparation and Application

Abstract

H2O2 is essential for cellular processes and plays a vital role in the regulation of cell signaling pathways, which can be viewed as a warning signal for many kinds of disease including cancer, cardiovascular disease, reproductive abnormalities, diabetes, and renal failure. A H2O2-responsive hydrogel (H2O2-Gel) is a promising candidate for biomedical applications because of its good biocompatibility, similarity to soft biological tissues, ease of preparation, and its ability to respond to H2O2. In this study, the H2O2-responsive moieties used to fabricate H2O2-Gels were reviewed, including thioethers, disulfide bonds, selenides, diselenium bonds, diketones, boronic, and others. Next, the preparation method of H2O2-Gel was divided into two major categories according to their reaction mechanisms: either self-crosslinking or mechanisms entailing the addition of difunctional crosslinkers. Last, the applications of H2O2-Gels were emphasized, which have been viewed as desirable candidates in the fields of drug delivery, the detection of H2O2, glucose-responsive systems, ROS scavengers, tissue engineering, and cell-encapsulation.

H2O2-Responsive Nanocarriers Prepared by RAFT-Mediated Polymerization-Induced Self-Assembly of N-(2-(Methylthio)ethyl)acrylamide for Biomedical Applications

“…One widely known phenomenon is the abnormal increase of reactive oxygen species (ROS), which induces oxidative stress and cell disruption, thus causing a variety of diseases such as cancer, diabetes, infections, and neurodegenerative diseases. − ROS are free-radical byproducts of oxygen metabolism during the cell regulation process, which plays a beneficial role in maintaining normal cellular activities at a concentration of 3–10 μM but promotes cellular dysregulation and diseases at 100 μM . Such a property has largely been exploited to design nanovehicles encoded with functionalities sensitive to the increased ROS, inducing molecular structural transitions or disassociation into subunits to release internal payloads at targeted sites. − In the context of ROS-responsive drug delivery systems, block copolymer NPs bearing thioether moieties have been widely studied in recent reports, since the hydrophobic thioether incorporated in the water-insoluble segments could be transformed into hydrophilic sulfoxides in the presence of oxidation species such as H 2 O 2 , promoting a solubility transition and disrupting the amphiphilic balance, to ultimately, disassociating block copolymers NPs to releasing their payloads. − …”

Responsive hydrogel dressings for intelligent wound management

“…-23 of 41 Despite the fact that ROS-responsive hydrogel dressings have shown encouraging improvements in the treatment of infected wounds, there are still certain barriers preventing the commercialization and clinical implementation of these gels owing to a lack of formal guidelines or criteria. [144] Due to the complexity of physiological fluids as well as individual differences in ROS levels, it is much more challenging to establish a correlation between in vitro and in vivo studies, which is seldom investigated but is still an important problem that needs to be addressed. Moreover, in-depth research is required since these gels often have issues with stability and possible toxicity of the by-products during degradation.…”

Redox-Responsive Comparison of Diselenide and Disulfide Core-Cross-Linked Micelles for Drug Delivery Application

“…In recent years, the diselenide bond has been considered the most appealing redoxresponsive cross-links due to its various benefits, such as its hydrolytic stability under physiological conditions and its low-bond energy (172 kJ/mol) relative to that of the disulfide bond (268 kJ/mol) [37,38]. The diselenide bond has a lower energy, which makes it more amenable to oxidation in the presence of hydrogen peroxide (H 2 O 2 ) during the phase conversion from hydrophobic diselenide to hydrophilic selenic acid [39].…”