Nanoparticles Containing Biocompatible Radicals Based on 1,2,4-Benzotriazinyl for Reactive Oxygen Species Scavenging in Living Cells

Abstract

We report the first demonstration using π-conjugated radicals for reactive oxygen species (ROS) scavenging. The ester-derived 1,2,4-benzotriazinyl monoradical VER and its carboxyl counterpart VAR exhibit typical antiferromagnetic behavior with a thermally populated spin-triplet state. Upon self-assembly with DSPE-PEG1000, VER formed ∼25 nm size nanoparticles (NPs) with good water dispersibility and stability, no obvious aggregation and degradation were observed after storing at ambient environment for 14 days. In contrast, VAR NPs were unstable and visible aggregates appeared on the seventh day. These radical NPs show good biocompatibility, there was almost no decrease in the cell viability after being incubated with either NPs even at a concentration of 100 μg/mL. Importantly, excessive ROS of the studied model RAW264.7 cells was scavenged to normal concentration when incubated with VER NPs, whereas ROS of VAR NPs treated model cells was almost not changed or even increased.

Regulation of Photophysical Behaviors in Hyperbranched Aggregation-Induced Emission Polymers for Reactive Oxygen Species Scavenging

“…Since biosafety is an essential issue before the assessment of effectiveness, the cytotoxicity of HBPSi-CBD and HBPSi-Met against NCM460 cells was studied via a CCK-8 assay. , According to Figure D, a slight cell viability change was observed after incubation with HBPSi-CBD or HBPSi-Met with various concentrations for 24 h. More than 78% NCM460 cells remain alive after being treated with HBPSi-CBD. Moreover, the cellular viabilities of HBPSi-Met treated cells (90% for 100 mg/mL) are higher than those of HBPSi-CBD treated cells, which can be attributed to the good antioxidant ability of HBPSi-Met in protecting cells from oxidative stress-induced damage.…”

“…28−30 Thus, various types of advanced materials serving as ROS scavengers have been developed to reduce the overproduced cellular ROS and treat the above physiological disorders, such as small organic molecules, 31 enzyme-like inorganic nanoparticles, 32,33 biomass-derived systems and responsive polymeric drug delivery systems. 34,35 However, these approaches generally meet challenges such as adverse effects, low structural stability, and complexity of the time-consuming synthesis. As an alternative to organic antioxidants, polymers bearing sulfur atoms have attracted particular attention.…”

“…Reactive oxygen species (ROS) are crucial molecules in various biological and biochemical pathways, which regulate cell metabolism by affecting the oxygen homeostasis and signaling process. − The upregulated level of ROS induces oxidative stress and is associated with metabolic dysfunction, including atherosclerosis, cardiovascular diseases, neurodegenerative disease, etc. − Thus, various types of advanced materials serving as ROS scavengers have been developed to reduce the overproduced cellular ROS and treat the above physiological disorders, such as small organic molecules, enzyme-like inorganic nanoparticles, , biomass-derived systems and responsive polymeric drug delivery systems. , However, these approaches generally meet challenges such as adverse effects, low structural stability, and complexity of the time-consuming synthesis. As an alternative to organic antioxidants, polymers bearing sulfur atoms have attracted particular attention. , The stable polymeric structures could prevent adverse effects and improve therapeutic efficacy, and the reductive thioether groups with hydrophobic-to-hydrophilic conversion when exposed to ROS make them ideal candidates for responsive drug delivery.…”