Development of Polymer-Encapsulated, Amine-Functionalized Zinc Ferrite Nanoparticles as MRI Contrast Agents.

The need for stable and well-defined magnetic nanoparticles is constantly increasing in biomedical applications; however, their preparation remains challenging. We used two different solvothermal methods (12 h reflux and a 4 min microwave, MW) to synthesize amine-functionalized zinc ferrite (ZnFe2O4-NH2) superparamagnetic nanoparticles. The morphological features of the two ferrite samples were the same, but the average particle size was slightly larger in the case of MW activation: 47 ± 14 nm (Refl.) vs. 63 ± 20 nm (MW). Phase identification measurements confirmed the exclusive presence of zinc ferrite with virtually the same magnetic properties. The Refl. samples had a zeta potential of -23.8 ± 4.4 mV, in contrast to the +7.6 ± 6.8 mV measured for the MW sample. To overcome stability problems in the colloidal phase, the ferrite nanoparticles were embedded in polyvinylpyrrolidone and could be easily redispersed in water. Two PVP-coated zinc ferrite samples were administered (1 mg/mL ZnFe2O4) in X BalbC mice and were compared as contrast agents in magnetic resonance imaging (MRI). After determining the r1/r2 ratio, the samples were compared to other commercially available contrast agents. Consistent with other SPION nanoparticles, our sample exhibits a concentrated presence in the hepatic region of the animals, with comparable biodistribution and pharmacokinetics suspected. Moreover, a small dose of 1.3 mg/body weight kg was found to be sufficient for effective imaging. It should also be noted that no toxic side effects were observed, making ZnFe2O4-NH2 advantageous for pharmaceutical formulations.

Correction: Synthesis and preclinical application of a Prussian blue-based dual fluorescent and magnetic contrast agent (CA).

[This corrects the article DOI: 10.1371/journal.pone.0264554.].

A novel ACE2 decoy for both neutralization of SARS-CoV-2 variants and killing of infected cells.

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) led to millions of infections and deaths worldwide. As this virus evolves rapidly, there is a high need for treatment options that can win the race against new emerging variants of concern. Here, we describe a novel immunotherapeutic drug based on the SARS-CoV-2 entry receptor ACE2 and provide experimental evidence that it cannot only be used for (i) neutralization of SARS-CoV-2 in vitro and in SARS-CoV-2-infected animal models but also for (ii) clearance of virus-infected cells. For the latter purpose, we equipped the ACE2 decoy with an epitope tag. Thereby, we converted it to an adapter molecule, which we successfully applied in the modular platforms UniMAB and UniCAR for retargeting of either unmodified or universal chimeric antigen receptor-modified immune effector cells. Our results pave the way for a clinical application of this novel ACE2 decoy, which will clearly improve COVID-19 treatment.

Synthesis and preclinical application of a Prussian blue-based dual fluorescent and magnetic contrast agent (CA).

The aim of this study was to develop and characterize a Prussian Blue based biocompatible and chemically stable T1 magnetic resonance imaging (MRI) contrast agent with near infrared (NIR) optical contrast for preclinical application. The physical properties of the Prussian blue nanoparticles (PBNPs) (iron (II); iron (III);octadecacyanide) were characterized with dynamic light scattering (DLS), zeta potential measurement, atomic force microscopy (AFM), and transmission electron microscopy (TEM). In vitro contrast enhancement properties of PBNPs were determined by MRI. In vivo T1-weighted contrast of the prepared PBNPs was investigated by MRI and optical imaging modality after intravenous administration into NMRI-Foxn1 nu/nu mice. The biodistribution studies showed the presence of PBNPs predominantly in the cardiovascular system. Briefly, in this paper we show a novel approach for the synthesis of PBNPs with enhanced iron content for T1 MRI contrast. This newly synthetized PBNP platform could lead to a new diagnostic agent, replacing the currently used Gadolinium based substances.

Scale-up of Electrospinning: Market Overview of Products and Devices for Pharmaceutical and Biomedical Purposes.

Recently, the electrospinning (ES) process has been extensively studied due to its potential applications in various fields, particularly pharmaceutical and biomedical purposes. The production rate using typical ES technology is usually around 0.01-1 g/h, which is lower than pharmaceutical industry production requirements. Therefore, different companies have worked to develop electrospinning equipment, technological solutions, and electrospun materials into large-scale production. Different approaches have been explored to scale-up the production mainly by increasing the nanofiber jet through multiple needles, free-surface technologies, and hybrid methods that use an additional energy source. Among them, needleless and centrifugal methods have gained the most attention and applications. Besides, the production rate reached (450 g/h in some cases) makes these methods feasible in the pharmaceutical industry. The present study overviews and compares the most recent ES approaches successfully developed for nanofibers' large-scale production and accompanying challenges with some examples of applied approaches in drug delivery systems. Besides, various types of commercial products and devices released to the markets have been mentioned.

Fluorescent, Prussian Blue-Based Biocompatible Nanoparticle System for Multimodal Imaging Contrast.

(1) Background. The main goal of this work was to develop a fluorescent dye-labelling technique for our previously described nanosized platform, citrate-coated Prussian blue (PB) nanoparticles (PBNPs). In addition, characteristics and stability of the PB nanoparticles labelled with fluorescent dyes were determined. (2) Methods. We adsorbed the fluorescent dyes Eosin Y and Rhodamine B and methylene blue (MB) to PB-nanoparticle systems. The physicochemical properties of these fluorescent dye-labeled PBNPs (iron(II);iron(III);octadecacyanide) were determined using atomic force microscopy, dynamic light scattering, zeta potential measurements, scanning- and transmission electron microscopy, X-ray diffraction, and Fourier-transformation infrared spectroscopy. A methylene-blue (MB) labelled, polyethylene-glycol stabilized PBNP platform was selected for further assessment of in vivo distribution and fluorescent imaging after intravenous administration in mice. (3) Results. The MB-labelled particles emitted a strong fluorescent signal at 662 nm. We found that the fluorescent light emission and steric stabilization made this PBNP-MB particle platform applicable for in vivo optical imaging. (4) Conclusion. We successfully produced a fluorescent and stable, Prussian blue-based nanosystem. The particles can be used as a platform for imaging contrast enhancement. In vivo stability and biodistribution studies revealed new aspects of the use of PBNPs.