Significance of PSCA as a novel prognostic marker and therapeutic target for cancer.

One of the contributing factors in the diagnosis and treatment of most cancers is the identification of their surface antigens. Cancer tissues or cells have their specific antigens. Some antigens that are present in many cancers elicit different functions. One of these antigens is the prostate stem cell antigen (PSCA) antigen, which was first identified in the prostate. PSCA is a cell surface protein that has different functions in different tissues. It can play an inhibitory role in cell proliferation as well as a tumor-inducing role. PSCA has several genetic variants involved in cancer susceptibility in some tissues, so identifying the characteristics of this antigen and its relationship with clinical features can provide more information on diagnosis and treatment of patients with cancers. Most studies on the PSCA have focused on prostate cancer. While it is also expressed in other cancers, little attention has been paid to its role as a valuable diagnostic, prognostic, and therapeutic tool in other cancers. PSCA has several genetic variants that seem to play a significant role in cancer susceptibility in some tissues, so identifying the characteristics of this antigen and its relationship and variants with clinical features can be beneficial in concomitant cancer therapy and diagnosis, as theranostic tools. In this study, we will review the alteration of the PSCA expression and its polymorphisms and evaluate its clinical and theranostics significance in various cancers.

Anti-oral cancer properties of potential probiotic lactobacilli isolated from traditional milk, cheese, and yogurt.

This study investigates the probiotic and anti-cancer effects of 21 isolated Lactobacillus strains from cheese, milk, and yogurt in Kermanshah, Iran, on oral cancer cell lines KB and OSCC. Four selected isolates (Y33, M45, C5, and C28) displayed good viability and resistance to specific antibiotics. Notably, strains C28 and Y33 exhibited the best results, showing susceptibility or semi-susceptibility to five antibiotics. Y33, with high cell surface hydrophobicity (62%), demonstrated significant anti-pathogenic activity, inhibiting the growth of tested pathogens and displaying strong adhesion to human intestinal Caco-2 cells (52%). Further assessments, including acridine orange/ethidium bromide staining and mRNA expression analysis, revealed four isolates (C5, C28, M45, and Y33) with promising probiotic properties. Particularly, Y33's protein-based extract metabolites showed dose- and time-dependent inhibition of KB and OSCC cancer cell lines, inducing apoptosis without significant cytotoxic effects on normal cells. Y33 (Lactiplantibacillus plantarum) exhibited the strongest probiotic potential, surpassing conventional anti-cancer drugs, suggesting its therapeutic potential for preventing oral cancer cell proliferation and improving survival rates in oral cancer patients.

A comprehensive review on nanocomposite biomaterials based on gelatin for bone tissue engineering.

The creation of a suitable scaffold is a crucial step in the process of bone tissue engineering (BTE). The scaffold, acting as an artificial extracellular matrix, plays a significant role in determining the fate of cells by affecting their proliferation and differentiation in BTE. Therefore, careful consideration should be given to the fabrication approach and materials used for scaffold preparation. Natural polypeptides such as gelatin and collagen have been widely used for this purpose. The unique properties of nanoparticles, which vary depending on their size, charge, and physicochemical properties, have demonstrated potential in solving various challenges encountered in BTE. Therefore, nanocomposite biomaterials consisting of polymers and nanoparticles have been extensively used for BTE. Gelatin has also been utilized in combination with other nanomaterials to apply for this purpose. Composites of gelatin with various types of nanoparticles are particularly promising for creating scaffolds with superior biological and physicochemical properties. This review explores the use of nanocomposite biomaterials based on gelatin and various types of nanoparticles together for applications in bone tissue engineering.

Enzymatically crosslinked magnetic starch-grafted poly(tannic acid) hydrogel for "smart" cancer treatment: An in vitro chemo/hyperthermia therapy study.

A novel strategy was designed and developed based of horseradish peroxidase (HRP)-mediated crosslinking of tyramine-functionalized starch (Tyr-St), tannic acid (TA) and phenolated-magnetic nanoparticles (Fe3O4-PhOH NPs), and simultaneous loading of doxorubicin hydrochloride (Dox) to afford a pH-responsive magnetic hydrogel-based drug delivery system (DDS) for synergistic in vitro chemo/hyperthermia therapy of human breast cancer (MCF-7) cells. The developed St-g-PTA/Fe3O4 magnetic hydrogel showed porous micro-structure with saturation magnetization (δs) value of 19.2 emu g-1 for Fe3O4 NPs content of ∼7.4 wt%. The pore sizes of the St-g-PTA/Fe3O4 hydrogel was calculated to be 2400 ± 200 nm-2. In vitro drug release experiments exhibited the developed DDS has pH-dependent drug release behavior, while at physiological pH (7.4) released only 30 % of the loaded drug after 100 h. Human serum albumin (HSA) adsorption capacities of the synthesized St/Fe3O4 and St-g-PTA/Fe3O4 magnetic hydrogels were obtained as 86 ± 2.2 and 77 ± 1.9 µgmg-1, respectively. The well-known MTT-assay approved the cytocompatibility of the developed St-g-PTA/Fe3O4 hydrogel, while the Dox-loaded system exhibited higher anti-cancer activity than those of the free Dox as verified by MTT-assay, and optical as well as florescent microscopies imaging. The synergistic chemo/hyperthermia therapy effect was also verified for the developed St-g-PTA/Fe3O4-Dox via hot water approach.

Targeted protein modification as a paradigm shift in drug discovery.

Targeted Protein Modification (TPM) is an umbrella term encompassing numerous tools and approaches that use bifunctional agents to induce a desired modification over the POI. The most well-known TPM mechanism is PROTAC-directed protein ubiquitination. PROTAC-based targeted degradation offers several advantages over conventional small-molecule inhibitors, has shifted the drug discovery paradigm, and is acquiring increasing interest as over ten PROTACs have entered clinical trials in the past few years. Targeting the protein of interest for proteasomal degradation by PROTACS was the pioneer of various toolboxes for selective protein degradation. Nowadays, the ever-increasing number of tools and strategies for modulating and modifying the POI has expanded far beyond protein degradation, which phosphorylation and de-phosphorylation of the protein of interest, targeted acetylation, and selective modification of protein O-GlcNAcylation are among them. These novel strategies have opened new avenues for achieving more precise outcomes while remaining feasible and minimizing side effects. This field, however, is still in its infancy and has a long way to precede widespread use and translation into clinical practice. Herein, we investigate the pros and cons of these novel strategies by exploring the latest advancements in this field. Ultimately, we briefly discuss the emerging potential applications of these innovations in cancer therapy, neurodegeneration, viral infections, and autoimmune and inflammatory diseases.

Extracellular matrix-mimetic electrically conductive nanofibrous scaffolds based on polyaniline-grafted tragacanth gum and poly(vinyl alcohol) for skin tissue engineering application.

As pivotal role of scaffold in tissue engineering (TE), the aim of present study was to design and development of extracellular matrix (ECM)-mimetic electrically conductive nanofibrous scaffolds composed of polyaniline-grafted tragacanth gum (TG-g-PANI) and poly(vinyl alcohol) (PVA) with different PANI content for skin tissue engineering (STE) application. The fabricated scaffolds were preliminary evaluated in terms of some physicochemical and biological properties. Cytocompatibility and cells proliferation properties of the scaffolds were examined with the well-known MTT assay, and it was found that the developed scaffolds have proper cytocompatibilities and can enhances the mouse fibroblast L929 cells adhesion as well as proliferation, which confirm their potential for STE applications. Hemocompatibility assay revealed that the hemolysis rate of the fabricated scaffolds were <2 % even at a relatively high concentration (200 µgmL-1) of samples, therefore, these scaffolds can be considered as safe. Human serum albumin (HSA) protein adsorption capacities of the fabricated scaffolds were quantified as 42 and 49 µgmg-1 that represent suitable values for a successful TE. Overall, the fabricated scaffold with 20 wt% of TG-g-PANI showed higher potential in both physicochemical and biological features than scaffold with 30 wt% of mentioned copolymer for STE application.

Biomimetic alginate-based electroconductive nanofibrous scaffolds for bone tissue engineering application.

Novel electrically conductive nanofibrous scaffolds were designed and fabricated through the grafting of aniline monomer onto a phenylamine-functionalized alginate (Alg-NH2) followed by electrospinning with poly(vinyl alcohol) (PVA). Performance of the prepared scaffolds in bone tissue engineering (TE) were studied in terms of physicochemical (e.g., conductivity, electroactivity, morphology, hydrophilicity, water uptake, and mechanical) and biological (cytocompatibility, in vitro biodegradability, cells attachment and proliferation, hemolysis, and protein adsorption) properties. The contact angles of the scaffolds with water drop were obtained about 50 to 60° that confirmed their excellent hydrophilicities for TE applications. Three dimensional (3D), inter-connected and uniform porous structures of the scaffolds without any bead formation was confirmed by scanning electron microscopy (SEM). Electrical conductivities of the fabricated scaffolds were obtained as 1.5 × 10-3 and 2.7 × 10-3 Scm-1. MTT assay results revealed that the scaffolds have acceptable cytocompatibilities and can enhance the cells adhesion as well as proliferation, which approved their potential for TE applications. Hemolysis rate of the developed scaffolds were quantified <2 % even at high concentration (200 µgmL-1) of samples that approved their hemocompatibilities. The scaffolds were also exhibited acceptable protein adsorption capacities (65 and 68 µgmg-1). As numerous experimental results, the developed scaffolds have acceptable potential for bone TE.

Recent advances in adsorption of environmental pollutants using metal-organic frameworks-based hydrogels.

Water pollution is increasing significantly owing to industrialization and population growth that lead to serious environmental and health issues. Therefore, the design and development of more effective wastewater treatment approaches are necessary due to a significant upsurge in demand for freshwater. More recently, metal-organic frameworks (MOFs) have attracted attention in environmental science owing to their tunable porosity, unique structure, flexibility, and various composition. Despite these attractive advantages, some drawbacks, including intrinsic fragility, unsatisfied processability, dust formation, and poor reusability, have greatly limited their applications. Therefore, MOFs are often designed as supported-based MOFs (e.g., MOFs-coated composites) or 3D structured composites, such as MOFs-based hydrogels. MOFs-based hydrogels are excellent candidates in the sorption process because of their appropriate adsorption capacity, porous structure, good mechanical properties, durability as well as biodegradable features. In this review, the removal of different pollutants (e.g., synthetic dyes, phosphates, heavy metals, antibiotics, and some organic compounds) from aqueous media has been studied by the adsorption process using MOFs-based hydrogels. The important advancements in the fabrication of MOFs-based hydrogels and their capacities in the adsorption of pollutants under experimental conditions have been discussed. Finally, problems and future perspectives on the adsorption process using MOFs-based hydrogels have been investigated.

Prospects for hypoxia-based drug delivery platforms for the elimination of advanced metastatic tumors: From 3D modeling to clinical concepts.

Hypoxia is a unique characteristic of the solid tumor microenvironment. Hypoxia contributes to multi-drug resistance, metastasis and cancer relapse through numerous molecular pathways, but at the same time provides an opportunity for the development of novel drugs or modalities specifically targeting hypoxic tumor regions. Given the high significance of tumor hypoxia in therapeutic results, we here discuss a variety of hypoxia-adopted strategies, and their potential and utility in the treatment of deep-seated hypoxic tumor cells. We discuss the merits and demerits of these approaches, as well as their combination with other approaches such as photodynamic therapy. We also survey the currently available 3D hypoxia modeling systems, in particular organoid-based microfluidics. Finally, we discuss the potential and the current status of preclinical tumor hypoxia approaches in clinical trials for advanced cancer. We believe that multi-modal imaging and therapeutic hypoxia adopted drug delivery platforms could provide better efficacy and safety profiles, and more importantly personalized therapy. Determining the hypoxia status of tumors could offer a second chance for the clinical translation of hypoxia-based agents, such as hypoxia activated prodrugs (HAPs) from bench to bedside.

Tumor microenvironment penetrating chitosan nanoparticles for elimination of cancer relapse and minimal residual disease.

Chitosan and its derivatives are among biomaterials with numerous medical applications, especially in cancer. Chitosan is amenable to forming innumerable shapes such as micelles, niosomes, hydrogels, nanoparticles, and scaffolds, among others. Chitosan derivatives can also bring unprecedented potential to cross numerous biological barriers. Combined with other biomaterials, hybrid and multitasking chitosan-based systems can be realized for many applications. These include controlled drug release, targeted drug delivery, post-surgery implants (immunovaccines), theranostics, biosensing of tumor-derived circulating materials, multimodal systems, and combination therapy platforms with the potential to eliminate bulk tumors as well as lingering tumor cells to treat minimal residual disease (MRD) and recurrent cancer. We first introduce different formats, derivatives, and properties of chitosan. Next, given the barriers to therapeutic efficacy in solid tumors, we review advanced formulations of chitosan modules as efficient drug delivery systems to overcome tumor heterogeneity, multi-drug resistance, MRD, and metastasis. Finally, we discuss chitosan NPs for clinical translation and treatment of recurrent cancer and their future perspective.

Administration of microencapsulated Enterococcus faecium ABRIINW.N7 with fructo-oligosaccharides and fenugreek on the mortality of tilapia challenged with Streptococcus agalactiae.

We investigated the probiotic potential of a microencapsulated Enterococcus faecium ABRIINW.N7 for control of Streptococcus agalactiae infection in hybrid (Oreochromis niloticus × Oreochromis mossambicus) red tilapia. A two-phase experiment approach was completed in which E. faecium bacteria were propagated, from which a culture was isolated, identified using molecular techniques, and microencapsulated to produce a stable commercial fructooligosaccharide (FOS) and fenugreek (Fk) product of optimal concentration. The FOS and Fk products were assessed in a 90-days in vivo challenge study, in which red hybrid tilapia were allocated to one of five treatments: (1) No Streptococcus agalactiae (Sa) challenge (CON); (2) Sa challenge only (CON+); (3) Sa challenge in a free cell (Free Cell); (4) Sa challenge with 0.8% (w/v) Alginate; (5) Microencapsulated FOS and Fk. In vitro results showed high encapsulation efficiency (≥98.6 ± 0.7%) and acceptable viability of probiotic bacteria within the simulated fish digestive system and high stability of viable cells in all gel formulations (34 < SR% <63). In vivo challenges demonstrated that the FOS and Fk products could be used to control S. agalactiae infection in tilapia fish and represented a novel investigation using microencapsulation E. faecium as a probiotic diet for tilapia fish to control S. agalactiae infection and to lower fish mortality. It is recommended that local herbal gums such as 0.2% Persian gum and 0.4% Fk in combination with 0.8% alginate (Formulation 7) can be used as a suitable scaffold and an ideal matrix for the encapsulation of probiotics. These herbal gums as prebiotics are capable of promoting the growth of probiotic cells in the food environment and digestive tract.

Simultaneous removal of cationic and anionic dyes from simulated industrial effluents using a nature-inspired adsorbent.

Alginate-grafted polyaniline (Alg-g-PANI) microparticles were synthesized through the grafting of aniline onto functionalized Alg followed by double crosslinking by glutaraldehyde and calcium chloride. The performance of the developed microparticles as adsorbent in simultaneous removal of malachite green (MG) and congo red (CR) dyes were examined by the batch method. Experimental parameters, including adsorbent amount, pH, initial dyes concentrations, and contact time were optimized. Langmuir and Freundlich adsorption models were employed to explore the equilibrium isotherm. As the Langmuir model results, the maximum adsorption capacities (Qm) of microparticles for the MG and CR dyes were obtained as 578.3 and 409.6 mgg-1, respectively. Adsorption kinetics for both dyes were well-fitted with the pseudo-second-order model that confirm the rate-limiting step might be the chemical adsorption. The adsorbent was regenerated via desorption process and was reusable five times without a substantial decrease in its adsorption efficacy in first three cycles. Adsorbent-dyes interactions were computationally evaluated using Gromacs package, and it was found that both MG and CR are able to interact strongly with the adsorbent. In accordance with experimental results, simulation data revealed that MG can be removed more efficiently than those of the CR. As the experimental results, we could conclude that the synthesized Alg-g-PANI microparticles can be used as a nature-inspired adsorbent for simultaneous removals of CR and MG dyes.

Sulfur functionality-modified starches: Review of synthesis strategies, properties, and applications.

Starch is the second most abundant naturally-occurring polymer after cellulose that possess superior physicochemical and biological features with numerous practical applications ranging from industrial to biomedical. Despite, native starch suffer from some drawbacks, including difficult processability, low shear and thermal stability, weak mechanical properties, and tendency to easily retrograde and undergo syneresis. Therefore, modification of native starch is necessary for circumvent the above-mentioned problems and expanding application ranges. This natural polymer can be modified using chemical, physical, enzymatic, and genetic engineering strategies. Amongst, chemical approaches have received more attention owing to enhancing physicochemical and biological features that lead to higher performance than those of the other strategies. In this context, incorporation of sulfur functionality-containing groups (sulfonation and sulfation) can be considered as an efficient approach due to significant enhancement in physiochemical properties, including zeta potential (move to negative values), molecular weight, processiability (e.g., solubility and meltability), and rheology. Furthermore, this strategy can modified some biological features, such as hemocompatibility, protein sorption, biostability, adhesion and proliferation of numerous cells, antithrombogenicity, antiinflammatory, antiviral, antimicrobial, antioxidant, antifungal, anticoagulant and antifouling properties. Accordingly, this review highlight's the synthesis strategies, physiochemical and biological properties, as well as applications of sulfur functionality-modified starches in numerous practical fields.

Green synthesis and biological activities assessment of some new chromeno[2,3-b]pyridine derivatives.

Magnetite nanoparticles (MNPs) composed of γ-Fe2O3 and hydroxyapatite (HAp) were modified by hexamethylen-1,6-diisocyanate (HMDI) followed by thiourea dioxide and used as recyclable catalyst for the synthesis of some newly derivatives of chromeno[2,3-b]pyridine. The products were synthesized in excellent yields via one-pot three-component reactions of 3-cyano-6-hydroxy-4-methyl-pyridin-2(1H)-one with aldehydes and dimedone under solvent-free conditions. The successful synthesis of products were confirmed using Fourier transform infrared (FTIR), proton/carbon nuclear magnetic resonance (1H/13C NMR), and mass spectroscopies as well as physical data (e.g., melting points and elemental composition). The in vitro antioxidant and antifungal activities of the synthesized samples were evaluated using scavenging effects on 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical and potato dextrose agar (PDA) medium, respectively. Based on results, the chromeno[2,3-b]pyridine derivatives exhibited excellent biological activities that qualified them for biomedical applications.

Hyaluronic acid-based drug nanocarriers as a novel drug delivery system for cancer chemotherapy: A systematic review.

Chemotherapy is the most common treatment strategy for cancer patients. Nevertheless, limited drug delivery to cancer cells, intolerable toxicity, and multiple drug resistance are constant challenges of chemotherapy. Novel targeted drug delivery strategies by using nanoparticles have attracted much attention due to reducing side effects and increasing drug efficacy. Therefore, the most important outcome of this study is to answer the question of whether active targeted HA-based drug nanocarriers have a significant effect on improving drug delivery to cancer cells.This study aimed to systematically review studies on the use of hyaluronic acid (HA)-based nanocarriers for chemotherapy drugs. The two databases MagIran and SID from Persian databases as well as international databases PubMed, WoS, Scopus, Science Direct, Embase, as well as Google Scholar were searched for human studies and cell lines and/or xenograft mice published without time limit until 2020. Keywords used to search included Nanoparticle, chemotherapy, HA, Hyaluronic acid, traditional medicine, natural medicine, chemotherapeutic drugs, natural compound, cancer treatment, and cancer. The quality of the studies was assessed by the STROBE checklist. Finally, studies consistent with inclusion criteria and with medium- to high-quality were included in the systematic review.According to the findings of studies, active targeted HA-based drug nanocarriers showed a significant effect on improving drug delivery to cancer cells. Also, the use of lipid nanoparticles with a suitable coating of HA have been introduced as biocompatible drug carriers with high potential for targeted drug delivery to the target tissue without affecting other tissues and reducing side effects. Enhanced drug delivery, increased therapeutic efficacy, increased cytotoxicity and significant inhibition of tumor growth, as well as high potential for targeted chemotherapy are also reported to be benefits of using HA-based nanocarriers for tumors with increased expression of CD44 receptor.

Fabrication of a dual stimuli-responsive magnetic nanohydrogel for delivery of anticancer drugs.

A dual stimuli-responsive magnetic nanohydrogel was fabricated as a potent drug delivery system (DDS) for 'smart' treatment of cancer by chemo/hyperthermia approach. For this objective, Fe3O4 nanoparticles (NPs) were produced via a co-precipitation approach and then modified by 3-(trimethoxysilyl) propylmethacrylate (MPS) moiety. The modified NPs were copolymerized with N,N'-(dimethylamino)ethyl methacrylate (DMAEMA), and maleic anhydride (MA) monomers by a free radical polymerization approach to afford a Fe3O4@P(DMAEMA-co-MA) core-shell NPs. Afterward, the NPs were shell crosslinked by the reaction of anhydride unites with neutralized cystamine (Cys). The fabricated pH- and reduction-responsive magnetic nanohydrogel was physically loaded with methotrexate (MTX), as an anticancer drug, and its drug loading efficiency (LE) was calculated as 64 ± 2.7%. The developed nanohydrogel/MTX exhibited proper stimuli-triggered drug release behavior that qualified it as an efficient DDS according to the abnormal micro-environment of cancerous tumors. The anticancer activity investigation using chemo/hyperthermia therapy approach by MTT-assay revealed that the nanohydrogel/MTX might show better clinical outcomes than those of the free MTX.

Preparation, physicochemical characterization, and anti-proliferative properties of Lawsone-loaded solid lipid nanoparticles.

Lawsone (LWS) is a naphthoquinone-type dye with potential antitumor activity. LWS is used in cosmetics for coloring hair, skin, and nails. In this study, solid lipid nanoparticles (SLNs) containing LWS were prepared using a hot homogenization technique. Physicochemical properties of LWS-SLNs including encapsulation efficiency (EE), drug loading (DL), size, zeta potential, homogeneity, in vitro release, and kinetics of release were determined. The potential cytotoxic properties of LWS-SLNs were investigated. Comet assay was done to assess the genotoxicity of LWS-SLNs. The scanning electron microscopy (SEM) images revealed that LWS-SLNs were spherical and homogeneously dispersed. The average diameter of free SLNs and LWS-SLNs were 97 ± 1.4 and 127 ± 3.1 nm, respectively with high EE% (95.88 ± 3.29) and a DL of 22.72 ± 1.39 mg/mL of LWS-SLNs. The plain LWS could induce growth inhibition of A549 cells with IC50 of 17.99 ± 1.11, 13.37 ± 1.22, and 9.21 ± 1.15 µg/mL after 24, 48, and 72 h, respectively, while LWS-SLNs had more cytotoxic effects after 48 h (9.81 ± 1.3 µg/mL). Comet assay represented clear fragmentation in the chromatin of the treated cells. Besides, LWS-SLNs (13.37 ± 1.22 µg/mL) induced ∼52 % apoptosis and even necrosis after 48 h. The qPCR results showed an enhanced downregulation of Bcl-2 and upregulation of Casp 9 due to the treatment of A549 cells with LSW-SLNs. In conclusion, a stable formulation of LWS-SLN was prepared with good physicochemical features and long-term biological effects that candidate it for in vivo trials.

Tarkhineh as a new microencapsulation matrix improves the quality and sensory characteristics of probiotic Lactococcus lactis KUMS-T18 enriched potato chips.

In the present study, probiotic potato chips containing a newly isolated probiotic Lactococcus lactis KUMS-T18 strain were produced by using a simple spraying method and then enhancing the stability, survival rate, and sensory characteristics of product during storage at 4 °C and 25 °C was examined for four months. Based on the results, Lactococcus lactis KUMS-T18 isolated from traditional Tarkhineh as a safe strain had high tolerance to low pH and high bile salt, anti-pathogenic activity, hydrophobicity, adhesion to human epithelial cells, auto- and co-aggregation, cholesterol assimilation and antibiotic susceptibility. Meanwhile, by micro-coating the probiotic cells in Tarkhineh formulations, elliptical to spherical shape (460-740 µm) probiotic drops were produced. The results revealed that potato chips produced with turmeric and plain Tarkhineh during storage at 4 °C, had excellent protection abilities for probiotic cells with about 4.52 and 3.46 log decreases in CFU/g respectively. On the other hand, probiotic potato chips, compared to non-probiotic and commercial potato chips, showed the criteria of probiotic products such as excellent quality and superior sensory characteristics. In summary, this study proved that probiotic Lactococcus lactis KUMS-T18 strain covered by Tarkhineh formulations as protective matrix has high potential to be used in the production of probiotic potato chips.

Preclinical studies conducted on nanozyme antioxidants: shortcomings and challenges based on US FDA regulations.

The wide prevalence of oxidative stress-induced diseases has led to a growing demand for antioxidant therapeutics worldwide. Nanozyme antioxidants are drawing enormous attention as practical alternatives for conventional antioxidants. The considerable body of research over the last decade and the promising results achieved signify the potential of nanozyme antioxidants to secure a place in the expanding market of antioxidant therapeutics. Nonetheless, there is no report on clinical trials for their further evaluation. Through analyzing in-depth selected papers which have conducted in vivo studies on nanozyme antioxidants, this review aims to pinpoint and discuss possible reasons impeding development of research toward clinical studies and to offer some practical solutions for future studies to bridge the gap between preclinical and clinical stages.

Lay abstract "We did not experience these kinds of strange illnesses in the past." Everybody might have heard such a familiar sentence from their grandparents and asked themselves, why? The current paper aims to provide readers with one of the answers: "Oxidative stress", which happens when the body fails to neutralize damage caused by unstable molecules called free radicals. In this paper, the authors present the seriousness of oxidative stress-induced clinical conditions. They discuss one of the promising treatments, nanozyme antioxidants, these are mostly based on nano-sized materials with enzyme-like function, in other words, they can speed up chemical reactions. Despite significant results, nanozyme antioxidants have not been investigated in clinical studies. This paper intends to search for the main reasons for this and suggest possible solutions.