A Broad‐Spectrum ROS‐Eliminating Material for Prevention of Inflammation and Drug‐Induced Organ Toxicity

Abstract

Despite the great potential of numerous antioxidants for pharmacotherapy of diseases associated with inflammation and oxidative stress, many challenges remain for their clinical translation. Herein, a superoxidase dismutase/catalase‐mimetic material based on Tempol and phenylboronic acid pinacol ester simultaneously conjugated β‐cyclodextrin (abbreviated as TPCD), which is capable of eliminating a broad spectrum of reactive oxygen species (ROS), is reported. TPCD can be easily synthesized by sequentially conjugating two functional moieties onto a β‐cyclodextrin scaffold. The thus developed pharmacologically active material may be easily produced into antioxidant and anti‐inflammatory nanoparticles, with tunable size. TPCD nanoparticles (TPCD NP) effectively protect macrophages from oxidative stress‐induced apoptosis in vitro. Consistently, TPCD NP shows superior efficacies in three murine models of inflammatory diseases, with respect to attenuating inflammatory responses and mitigating oxidative stress. TPCD NP can also protect mice from drug‐induced organ toxicity. Besides the passive targeting effect, the broad spectrum ROS‐scavenging capability contributes to the therapeutic benefits of TPCD NP. Importantly, in vitro and in vivo preliminary experiments demonstrate the good safety profile of TPCD NP. Consequently, TPCD in its native and nanoparticle forms can be further developed as efficacious and safe therapies for treatment of inflammation and oxidative stress‐associated diseases.

Enabling topical and long-term anti-radical properties for percutaneous coronary intervention-related complications by incorporating TEMPOL into electrospun nanofibers

“…As shown in Fig. 1f, a characteristic triplet signal of the nitroxyl radical was observed clearly, confirming the presence of TEMPOL radicals in the electrospun membranes [34,35]. Moreover, the loading amount of TEMPOL can be adjusted by simply varying the concentration of TEMPOL solution (i.e., the core layer spinning solution).…”

A Proresolving Peptide Nanotherapy for Site‐Specific Treatment of Inflammatory Bowel Disease by Regulating Proinflammatory Microenvironment and Gut Microbiota

“…Compared to ROS‐responsive nanocarriers based on other materials, such as poly(propylene sulfide), selenium‐containing copolymers, polydopamine, and materials bearing polythioether ketal or thioketal linkers, OxbCD‐derived NPs are highly sensitive to H 2 O 2 . More importantly, our comprehensive in vitro and in vivo studies have revealed good safety profile for nanocarriers based on OxbCD . Consequently, we hypothesize that the ROS‐responsive nanocarrier ON can revive orally delivered Ac2‐26 by protecting it from degradation and selective release in the inflamed colon of IBD.…”

“…[51] Consistently, we found complete hydrolysis of Ac2-26 after it was incubated in different solutions simulating gastric/intestinal fluids. [30][31][32][33][34]36,54,55] Consequently, we hypothesize that the ROS-responsive nanocarrier ON can revive orally delivered Ac2-26 by protecting it from degradation and selective release in the inflamed colon of IBD. [30,31] Compared to ROS-responsive nanocarriers based on other materials, such as poly(propylene sulfide), selenium-containing copolymers, polydopamine, and materials bearing polythioether ketal or thioketal linkers, [52,53] OxbCD-derived NPs are highly sensitive to H 2 O 2 .…”

Cyclodextrin‐Derived Intrinsically Bioactive Nanoparticles for Treatment of Acute and Chronic Inflammatory Diseases

“…Recently, anti‐inflammatory materials have been investigated as therapeutics against inflammation‐associated diseases. For example, nanoparticles (NPs) capable of eliminating reactive oxygen species (ROS) have demonstrated their efficacy in animal models of peritonitis, rheumatoid arthritis, colitis, nonalcoholic steatohepatitis, acute lung injury, sepsis, atherosclerosis, and ischemic stroke . NPs assembled by PEGylated bilirubin can function as a potent anti‐inflammatory nanotherapy for the treatment of colitis and asthma, by effectively scavenging ROS and modulating the immune system.…”