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.

Biomedical Applications of Zeolitic Nanoparticles, with an Emphasis on Medical Interventions.

The advent of porous materials, in particular zeolitic nanoparticles, has opened up unprecedented putative research avenues in nanomedicine. Zeolites with intracrystal mesopores are low framework density aluminosilicates possessing a regular porous structure along with intricate channels. Their unique physiochemical as well as physiological parameters necessitate a comprehensive overview on their classifications, fabrication platforms, cellular/macromolecular interactions, and eventually their prospective biomedical applications through illustrating the challenges and opportunities in different integrative medical and pharmaceutical fields. More particularly, an update on recent advances in zeolite-accommodated drug delivery and the prevalent challenges regarding these molecular sieves is to be presented. In conclusion, strategies to accelerate the translation of these porous materials from bench to bedside along with common overlooked physiological and pharmacological factors of zeolite nanoparticles are discussed and debated. Furthermore, for zeolite nanoparticles, it is a matter of crucial importance, in terms of biosafety and nanotoxicology, to appreciate the zeolite-bio interface once the zeolite nanoparticles are exposed to the bio-macromolecules in biological media. We specifically shed light on interactions of zeolite nanoparticles with fibrinogen and amyloid beta which had been comprehensively investigated in our recent reports. Given the significance of zeolite nanoparticles' interactions with serum or interstitial proteins conferring them new biological identity, the preliminary approaches for deeper understanding of administration, distribution, metabolism and excretion of zeolite nanoparticles are elucidated.

Bioaerogels: Synthesis approaches, cellular uptake, and the biomedical applications.

Aerogels are a class of porous structures with promising physicochemical properties. Among aerogels with various origins, polysaccharide aerogels (e.g., cellulose, chitosan, alginate, starch, agar, and so on) have received more attention. This group of aerogels can be classified as bioaerogels, which are originated from natural, semi-synthetic, and synthetic sources with exceptional biomedical applications. This review focuses on bioaerogels from the viewpoints of synthesis approaches, cellular uptake, toxicity, biodegradability, and the biomedical application perspectives.

Sonochemical in situ immobilization of Pd nanoparticles on green tea extract coated Fe3O4 nanoparticles: An efficient and magnetically recyclable nanocatalyst for synthesis of biphenyl compounds under ultrasound irradiations.

This work describes (i) an eco-friendly approach for in situ immobilization of Pd nanoparticles on the surface of Fe3O4 nanoparticles, with help of green tea extract and ultrasound irradiations, without using any toxic reducing agents and (ii) development of ultrasound assisted simple protocol for synthesis of biphenyl compounds. The structural, morphological and physicochemical characteristics of the catalyst were determined by different analytical methods including inductively coupled plasma (ICP) analysis, Fourier transform infrared spectroscopy (FT-IR), field emission scanning electron microscopy (FESEM), energy dispersive X-ray spectroscopy (EDS), transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS) and vibrating sample magnetometry (VSM). Catalytic performance of Pd/Fe3O4 NPs as magnetic and heterogeneous catalyst was evaluated in synthesis of various biphenyl compounds throughout Suzuki coupling reactions by using the ultrasound-assisted method that was developed in this study. The Pd/Fe3O4 NPs demonstrated a noticeable catalytic activity by giving high product yields. Furthermore, the heterogeneous nanocatalyst was successfully recovered up to six times without significant activity loss. Additionally, with respect to conventional coupling reactions, the ultrasound-assisted synthesis reactions presented the advantages of green conditions, short reaction times, high yields and easier work-up.

Glutathione conjugated polyethylenimine on the surface of Fe3O4 magnetic nanoparticles as a theranostic agent for targeted and controlled curcumin delivery.

Theranostics with the ability to simultaneous monitoring of treatment progress and controlled delivery of therapeutic agents has become as an emerging therapeutic paradigm in cancer therapy. In this study, we have developed a novel surface functionalized iron oxide nanoparticle using polyethyleneimine and glutathione for targeted curcumin (CUR) delivery and acceptable pH sensitive character. The developed magnetic nanoparticles (MNPs) were physicochemically characterized by FT-IR, XRD, FE-SEM and TEM. The MNPs was obtained in spherical shape with diameter of 50 nm. CUR was efficiently loaded into the MNPs and then in vitro release analyses were evaluated and showed that the prepared MNPs could release higher amount of CUR in acidic medium compared to neutral medium due to the pH sensitive property of the coated polymer. MTT assay confirmed the superior toxicity of CUR loaded MNPs compared to the control nanoparticles. Higher cellular uptake of the MNPs than negative control cells was demonstrated in SK-N-MC cell line. In vitro assessment of MRI properties showed that synthesized MNPs could be used as MRI imaging agent. Furthermore, according to hemolysis assay, the developed formulation exhibited suitable hemocompatibility. In vivo blood circulation analysis of the MNPs also exhibited enhanced serum bioavailability up to 2.5 fold for CUR loaded MNPs compared with free CUR.

Curcumin-lipoic acid conjugate as a promising anticancer agent on the surface of gold­iron oxide nanocomposites: A pH-sensitive targeted drug delivery system for brain cancer theranostics.

Brain tumor is a lethal, fast growing cancer and a difficult case for treatment. Receptor-mediated endocytosis has been recognized as one of the most effective methods for drug delivery to brain tissue by overcoming obstacles associated with conventional therapeutics. In this work, a targeted theranostic drug delivery system (DDS) was prepared based on gold­iron oxide nanocomposites (Fe3O4@Au NCs). Lipoic acid-curcumin (LA-CUR) was synthesized and introduced as a novel anticancer drug, and glutathione (GSH) was exploited as the targeting ligand. Both LA-CUR and GSH were easily attached to Fe3O4@Au NCs via Au-S interaction. As a negatively charged nanocarrier, the prepared DDS showed relatively less protein adsorption. Accordingly, hemocompatibility assays (complement, platelet, and leucocyte activation) revealed its hemocompatible virtue, especially in respect of free LA-CUR. GSH functionalization led to 2-fold increase of cellular uptake in GSH receptor-positive astrocyte cells which could primarily indicate the probable ability of the DDS to bypass BBB. Cytotoxicity and apoptosis assays together showed the noticeably enhanced cytotoxicity of LA-CUR against cancerous U87MG cells (IC50=2.69µg/ml) in comparison with curcumin (IC50=21.31µg/ml); moreover, the DDS demonstrated relatively higher cytotoxicity against cancerous U87MG cells than normal astrocyte cells which was in accordance with pH sensitive mechanism of LA-CUR release. Besides, the results of in vitro magnetic resonance imaging (MRI) (relaxation rate (r2)=80.73 (s-1·mM-1)) primarily revealed that the DDS can be applied as a negative MRI contrast agent. In sum, the prepared DDS appeared to be a promising candidate for brain cancer treatment and a favorable MRI contrast agent.