Oxidation‐Responsive Materials: Biological Rationale, State of the Art, Multiple Responsiveness, and Open Issues

Abstract

In this review, a general introduction to biological oxidants (focusing on reactive oxygen species, ROS) and the biomedical rationale behind the development of materials capable of responding to ROS is provided. The state of the art for preparative aspects and mechanistic responses of the most commonly used macromolecular ROS‐responsive systems, including polysulfides, polyselenides, polythioketals, polyoxalates, and also oligoproline‐ and catechol‐based materials, is subsequently given. The endowment of multiple responsiveness, with specific emphasis on the cases where a molecular logic gate behavior can be obtained, is focused on. Finally, fundamental open issues, which include implications of the “drug”‐like character of ROS‐responsive materials (inherent anti‐inflammatory behavior) and the poor quantitative understanding of ROS roles in biology, are discussed.

Reactive Oxygen Species‐Responsive Nanoparticles for the Treatment of Ischemic Stroke

“…The NP surface is coated with poly(ethylene glycol) (PEG) chains, from the surfactant used in their preparation (Pluronic F127); this composition was chosen to allow for biocompatibility and long circulation times in vivo; a graphic sketch of the nanoparticle synthetic method is shown in Scheme , and size distribution, cryo‐EM and zeta potential are provided in Figure S3 and Table S1, Supporting Information. The core is made of chemically cross‐linked PPS, which is an organic polymer with a high density of sulfur (II) atoms (sulfides, also known as thioethers); such groups are potent ROS scavengers, for example, methionine residues offer a well‐known biological example of this activity . Upon exposure to ROS, the sulfide groups can be converted to more polar and thus more hydrophilic groups (sulfoxides, sulfones).…”

Main Chain Polysulfoxides as Active ‘Stealth’ Polymers with Additional Antioxidant and Anti-Inflammatory Behaviour

“…Our group has a long-running activity on oxidation-sensitive polymers [42]. We have specifically focused on polysulfides, employing them as reactive oxygen species (ROS)-scavengers, and as a result as anti-inflammatory agents [43,44].…”

Synthesis, Characterization, and In Vitro Studies of an Reactive Oxygen Species (ROS)-Responsive Methoxy Polyethylene Glycol-Thioketal-Melphalan Prodrug for Glioblastoma Treatment

“…Furthering this technology by creating a prodrug which is activated as a consequence of a pathological stimulus to improve locoregional and site-specific delivery could be an intelligent approach and has been widely reviewed (Weidle et al, 2014;Taresco et al, 2018;Zeng et al, 2018) and investigated for GBM treatment (Taresco et al, 2018). The innovation would consist of inserting a linker between PEG and a drug that responds to a pathologic stimulus, thus improving the selectivity as well as the effectivity of the drug (Chang et al, 2016).…”

“…The innovation would consist of inserting a linker between PEG and a drug that responds to a pathologic stimulus, thus improving the selectivity as well as the effectivity of the drug (Chang et al, 2016). TK linkers are biocompatible linkers which are degraded to thiol-containing groups upon exposure to the most relevant ROS (hydroxyl radical, H 2 O 2 , and superoxide) (Shim and Xia, 2013;El-Mohtadi et al, 2019), and have been recently used in the design of ROSresponsive DDS for the delivery of drugs, siRNA, and DNA in cancer and inflammatory diseases. To our knowledge, TK-based ROS-responsive DDS for the treatment of GBM have not been previously developed (Lee et al, 2013;Zheng et al 2019).…”