The potential of oxygen and nitrogen species-regulating drug delivery systems in medicine

Abstract

The focus of this review is to present most significant advances in biomaterials used for control of reactive oxygen/nitrogen species (ROS/RNS, RONS) in medicine. A summary of the main pathways of ROS production and the main pathways of RNS production are shown herein. Although the physiological and pathological roles of RONS have been known for at least 2decades, the potential of their control in management of disease went unappreciated. Recently, advances in the field of biochemical engineering and materials science have allowed for development of RONS-responsive biomaterials for biomedical applications, which aim to control and change levels of reactive species in tissue microenvironments. These materials utilize polymers, inorganic nanoparticles (NPs), or organic-inorganic hybrids. Thus, biomaterials like hydrogels have been developed to promote tissue regeneration by actively scavenging and reducing RONS levels. Their promising utility comes from thermo- and RONS-sensitivity, stability as a delivery-medium, ease for incorporation into other materials and facility for injection. Their particular attractiveness is attributed to drug release realized in targeted tissues and cells with elevated RONS levels, which leads to enhanced treatment outcomes and reduced adverse effects. The mechanism of their action depends on the functional groups employed and their response to oxidation, and may be based on solubility changes or cleavage of chemical bonds. When talking about antioxidants, one should also mention oxidative stress, which we call the imbalance between antioxidants and reactive oxygen species, which occurs due to a deficiency of endogenous antioxidants and a low supply of exogenous antioxidants. This study is a review of articles in English from the databases PubMed and Web of Science retrieved by applying the search terms “Oxygen Species, Nitrogen Species and biomaterials” from 1996 to 2021.

Pro‐fluorescent probe with morpholine moiety and its reactivity towards selected biological oxidants

“…As previously described, SOD competes with • NO in the reaction with O 2 •− , which prevents O 2 •− from reacting with • NO to form the highly reactive peroxynitrite [15]. As a result, O 2 •– is rapidly converted to H 2 O 2 , and this process is accelerated by SOD [37–39]. This suggests that ONOO − formed in situ from • NO and O 2 •− is responsible for the oxidation of MpC‐BA to MpC‐OH .…”

“…•is rapidly converted to H 2 O 2 , and this process is accelerated by SOD [37][38][39]. This suggests that ONOO À formed in situ from • NO and O 2 •À is responsible for the oxidation of MpC-BA to MpC-OH.…”

Cold Physical Plasma-Mediated Fenretinide Prodrug Activation Confers Additive Cytotoxicity in Epithelial Cells

“…RONS-responsive prodrugs can be activated depending on the chemical structure of the boronate group, the concentration and reactivity of RONS, the pH, and the presence of other (bio-) molecules or antioxidants in the cell culture medium or solution [ 8 , 10 ]. Biologically inactive prodrugs can be converted into cytotoxic drugs upon RONS generation by metabolic processes in the tumor microenvironment through “triggered release” mechanisms.…”

“…In addition, some prodrugs, for instance, the aromatic nitrogen mustard prodrug [ 5 ] and belinostat prodrug [ 6 ], undergo a 1,6-elimination reaction that involves the cleavage of a quinone methide moiety and the release of the final parent drug ( Figure 1 A(b,c)). Alternatively, RONS can be produced via photo-redox reactions, generating, e.g., hydrogen peroxide (H 2 O 2 ), peroxynitrite (ONOO − ), and hypochlorite (ClO − ) [ 10 , 11 ]. Moreover, the stability of (aryl)boronic acid and ester-based prodrugs can be controlled, depending on the parent drug structure, pH, temperature, and concentration in the solution [ 12 , 13 ].…”