Scavenging ROS: Superoxide Dismutase/Catalase Mimetics by the Use of an Oxidation-Sensitive Nanocarrier/Enzyme Conjugate

Abstract

Reactive Oxygen Species (ROS) are quintessential inflammatory compounds with oxidizing behavior. We have successfully developed a micellar system with responsiveness at the same time to two of the most important ROS: superoxide and hydrogen peroxide. This allows for an effective and selective capture of the two compounds and, in perspective, for inflammation-responsive drug release. The system is composed of superoxide dismutase (SOD) conjugated to oxidation-sensitive amphiphilic polysulfide/PEG block copolymers; the conjugate combines the SOD reactivity toward superoxide with that of hydrophobic thioethers toward hydrogen peroxide. Specifically, here we have demonstrated how this hybrid system can efficiently convert superoxide into hydrogen peroxide, which is then "mopped-up" by the polysulfides: this modus operandi is functionally analogous to the SOD/catalase combination, with the advantages of (a) being based on a single and more stable system, and (b) a higher overall efficiency due the physical proximity of the two ROS-reactive centers (SOD and polysulfides).

Radiation resistance: Cancer stem cells (CSCs) and their enigmatic pro-survival signaling

“…The ROS play important physiological roles (in cell proliferation, differentiation, metabolism, cell death, tumorigenesis, cell-cell adhesion, and cell motility [40,41]); intracellular ROS levels are permanently regulated by ROS scavengers [14,37]. Various families of enzymes act to reduce the concentration of ROS: these include superoxide dismutase [42], superoxide reductase [38], catalase [43], glutathione peroxidase [44], glutathione reductase [38] and the multifunctional protein apurinic/apirimidinic endonuclease/redox effector factor (Ape1/Ref-1, also known as APEX1) [45]. Intracellular ROS also act as messengers in the molecular signaling that regulates the activities of the following intracellular pathways: MAPK-Erk, PI3K-Akt cascades, IB kinase-NFB and Src-dependent pathways [38].…”

Reactive oxygen species and glutathione dual redox-responsive micelles for selective cytotoxicity of cancer

“…In another study, N. Murthy et al [18] and Y. Xia et al [19] developed the ROS responsive thioketal for gene delivery. Works by A. Almutairi et al [20] and N. Tirelli et al [21] used polysulfide to treat inflammation. However, few ROS-sensitive particles exhibit drug release under the relevant H 2 O 2 concentrations of tumor cells [17].…”

Co-Immobilization of Superoxide Dismutase with Catalase on Soft Microparticles Formed by Self-Assembly of Amphiphilic Poly(Aspartic Acid)

“…Superoxide, peroxide, and hydroxyl radical are main components of reactive oxygen species (ROS), and are formed during oxygen metabolism [1]. ROS are involved in the progression of aging as well as neurodegenerative diseases, vascular and cancer diseases, and diabetes [2].…”

“…SOD is considered as the first line of defense against oxidative stress. The enzyme has antiaging, antiviral, and anti-inflammatory effects [1,2,6]. SOD has been widely applied in the cosmetics, pharmaceutical, and food industries [6].…”