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Innovative Medicines & Omics Antioxidant nanomedicines for therapies

2O 2H HO O (II) nanomedicines can further undergo surface modification
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process to be conferred with enhanced physiological
2HO 2HO O 2 (III) stability and targeting property.
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Our research group has proposed the concept of
These antioxidant defense systems scavenge excessive
ROS generated from cellular metabolic processes, “nanocatalytic medicine” in 2019, which is aimed at
maintaining a dynamic redox balance. However, under developing nanomedicines with catalytic activities to
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pathological circumstances when ROS generation exceeds trigger in situ catalytic reactions at pathological sites and
the scavenging capacity of the antioxidant defense systems, regulate local ROS concentration for achieving disease
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the homeostasis will be disrupted, causing oxidative stress treatment. Till now, numbers of nanocatalysts with
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in cells and subsequently the changes of downstream antioxidative properties, such as CeO nanoparticles,
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biological processes (such as immunologic process) and Mn O nanoparticles, RuO nanoparticles, and
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local microenvironments. Based on the pathogenesis, Prussian blue nanoparticles, have been applied for
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the oxidative stress-related diseases can be generally disease treatments. These nanocatalysts present SOD and
divided into five categories: (i) Autoimmune diseases catalase-like activities to catalyze the disproportionation
•−
(e.g., rheumatoid arthritis and inflammatory bowel of O and H O , during which the structural and
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disease), (ii) degenerative diseases (e.g., osteoarthritis, compositional characteristics of these nanocatalysts will
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osteoporosis, Alzheimer’s disease, and Parkinson’s not change, which may provide a sustainable therapeutic
disease), (iii) ischemia and ischemia-reperfusion injuries approach.
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(e.g., ischemic stroke, myocardial infarction, and acute In the past 5 years, numbers of antioxidant
kidney injury), (iv) metabolic diseases (e.g., diabetic nanomedicines with varied sizes, structures, and
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chronic wounds), and (v) infection-related diseases compositions have been constructed, for the treatment
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(e.g., pneumonia and sepsis). 17,18 As the overexpression of oxidative stress-related cardiovascular diseases, bone
of ROS is the common and key etiology of these diseases, diseases, brain diseases, kidney diseases, lung diseases,
antioxidant treatments will take effects in the detoxification liver diseases, ocular diseases, intestinal diseases, skin
and modulation of microenvironments for the treatments diseases, etc. (Figure 2). These nanomedicines with
of pathological abnormalities. 19,20 multi-functionality can overcome the disadvantages
Several small-molecule antioxidants have been of conventional antioxidants and improve therapeutic
approved by the U.S. Food and Drug Administration efficacies. In this comprehensive review, we will provide an
(FDA) for treating oxidative stress-related diseases, such integrated summary on the recent progresses made in the
as N-acetylcysteine, coenzyme Q10, edaravone, Vitamin C design, fabrication, and medical application of antioxidant
(ascorbic acid), and Vitamin E (Figure 1). However, the nanomedicines, based on the reports from diverse research
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efficacies of these antioxidants are not desirable due to groups including our group until 2023. Especially, the
their nonspecific distribution, low delivery efficiency, rapid underlying chemical mechanisms by which nanomedicines
renal clearance, and low stability. The administrations of scavenge excessive ROS and remove the pathogeny of ROS
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natural antioxidases are not applicable for therapy due to overexpression will be elucidated in-depth, and the unique
their over-large sizes resulting in short circulating half-life, advantages of these nanomedicines for disease treatments
poor cell permeability, and antigenicity. In addition, the will be highlighted.
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conditions required by natural antioxidases for catalysis Following our previous demonstration on ROS-based
are very stringent, and their thermal/chemical stabilities nanomedicines (mainly ROS-generating nanomedicines
are poor, making these enzymes easily deactivated in for cancer therapy), this review will focus specifically
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complicated physiological environments. on ROS-scavenging nanomedicines that improve the
The development of nanomedicine has provided therapeutic outcomes of multiple oxidative stress-related
additional strategies for treating oxidative stress-related diseases beyond cancer, hoping to depict a general
diseases. Some nanomedicines are constructed using antioxidative detoxification strategy for treating these
nanocarriers to load small-molecule antioxidants or diseases. In the next sections, we will elucidate the
antioxidases, thereby protecting these antioxidants from design principles of antioxidant nanomedicines, present
external environments and prolonging their circulating paradigms of antioxidant nanomedicines according to
half-lifes. Some nanomedicines are constructed using the types of diseases, with the emphasis on their redox
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nanoparticles with intrinsic antioxidative properties, behaviors that enable efficient ROS scavenging and
which are capable of scavenging ROS through non- microenvironment modulation at pathological sites.
catalytic or catalytic reactions. 25,26 All these antioxidant Key scientific issues encountered in the development
Volume 1 Issue 1 (2024) 2 doi: 10.36922/imo.2527