Antioxidant Nanotherapies for the Treatment of Inflammatory Diseases

Abstract

Reactive oxygen species (ROS) are essential in regulating various physiological functions. However, overproduction of ROS is implicated in the pathogenesis of various inflammatory diseases. Antioxidant therapy has thus represented an effective strategy for the treatment of oxidative stress relevant inflammatory diseases. Conventional anti-oxidative agents showed limited in vivo effects owing to their non-specific distribution and low retention in disease sites. Over the past decades, significant achievements have been made in the development of antioxidant nanotherapies that exhibit multiple advantages such as excellent pharmacokinetics, stable anti-oxidative activity, and intrinsic ROS-scavenging properties. This review provides a comprehensive overview on recent advances in antioxidant nanotherapies, including ROS-scavenging inorganic nanoparticles, organic nanoparticles with intrinsic antioxidant activity, and drug-loaded anti-oxidant nanoparticles. We highlight the biomedical applications of antioxidant nanotherapies in the treatment of different inflammatory diseases, with an emphasis on inflammatory bowel disease, cardiovascular disease, and brain diseases. Current challenges and future perspectives to promote clinical translation of antioxidant nanotherapies are also briefly discussed.

The Impact of Oxidative Stress in Human Pathology: Focus on Gastrointestinal Disorders

“…In particular, nanomaterials can be designed in such a way as to have antioxidant properties themselves, thus acting as nano-antioxidants, or as carriers and/or containers of natural compounds with antioxidant activity, mainly polyphenols [ 199 ]. Many literature data have reported the use of exosomes, lipid, and magnetic polymers; natural and synthetic polymers; ultrasonic microtubules; and nanoemulsions for the targeted release of antioxidants, in particular curcumin [ 200 , 201 , 202 ], resveratrol, and vitamin E [ 203 ] in the treatment of gastrointestinal inflammation, mostly IBD [ 204 ] and gastric ulceration [ 205 ]. It is very important to note that, although the use of nanostructures is associated with better bioavailability or enhancing pharmacokinetics, at high concentrations, they could be very toxic, releasing the drug out of control, and increasing oxidative stress through the generation of ROS.…”

Nanomaterials-Mediated Immunomodulation for Cancer Therapeutics

“…The in-depth knowledge about the components of the immune system and their role in regulating numerous diseases when combined with the recent technological advancement in the field of fabrication of safe and biocompatible NMs have revolutionized the biomedical applications of nanomaterials. Nanomaterial-based therapies have been applied for the treatment of autoimmune diseases ( Gao et al, 2017 ; Kwiatkowski et al, 2020 ), neurodegenerative diseases ( Fornaguera et al, 2015 ; Turjeman et al, 2015 ), inflammatory diseases ( Li, C. W. et al, 2020 ; Tran et al, 2015 ), and cancer ( Xin et al, 2017 ; Samanta et al, 2019 ). When introduced in vivo , NMs act as foreign entities and consequently lead to various immune responses.…”

Raising the ‘Good’ Oxidants for Immune Protection

“…Moreover, several disease-causing genetic variants and disease-associated genetic risk factors have shed light on the harmful consequences of insufficient ROS production for H 2 O 2 -induced oxidative modifications, redox signaling and host defense (e.g., CGD, hypothyroidism, inflammatory bowel disease) (33). To date most strategies targeting oxidative stress (i.e., antioxidant therapy) are based on the delivery of ROS scavengers, ROS converting or degrading compounds or on non-selective enzyme inhibitors to protect tissues and organs, but clinical results of antioxidant treatments in inflammatory diseases have so far been disappointing (182)(183)(184). More recently, treatments aimed at generating excessive concentrations of ROS or at inhibiting cellular antioxidant defense systems at a designated target location (i.e., prooxidant therapy) have been developed to promote cancer cell death or antimicrobial killing through oxidative damage (185,186).…”