László Forgách

Objectives: Magnetic nanoparticles are promising candidates for T2-weighted magnetic resonance imaging (MRI), but their physicochemical stability and biological compatibility remain important challenges for biomedical applications. Methods: In this study, amine-functionalized manganese ferrite (MnFe₂O₄) nanoparticles were coated with Prussian blue (PB) and subsequently formulated with bovine serum albumin (BSA). The resulting formulation was characterized using X-ray diffraction, transmission electron microscopy, X-ray photoelectron spectroscopy, Fourier-transform infrared spectroscopy, magnetic measurements, dynamic light scattering, molecular dynamics simulations, cytocompatibility assays, and MRI relaxometry. Results: The BSA-formulated nanoparticles were readily redispersed after lyophilization and remained colloidally stable throughout the 6 h observation period in the tested aqueous media. Molecular dynamics simulations demonstrated persistent close contacts between the MnFe₂O₄ surface and BSA residues, supporting stable nanoparticle–protein association. MRI relaxometry showed predominantly T2-weighted contrast behavior, with substantially higher r₂ than r₁ relaxivity. In vitro metabolic activity measurements demonstrated higher relative metabolic activity for the PB-coated formulation than for the corresponding uncoated formulation within the BSA-formulated systems. A pilot in vivo MRI experiment performed in a single mouse demonstrated rapid hepatic accumulation, with a detectable reduction in liver signal intensity within 10 min after administration and persistence of the hepatic signal change at the following-day measurement. Conclusions: These preliminary findings support further investigation of BSA-formulated PB-coated MnFe₂O₄ nanoparticles as a potential T2-weighted MRI contrast platform.

Background/Objectives: Palladium-103 (¹⁰³Pd) is an Auger electron-emitting radionuclide with nanometer-scale penetration ranges that result in highly localized energy deposition, making it well suited for molecularly targeted radionuclide therapy. However, efficient production, separation, and in vivo evaluation workflows remain limited. This study aimed to establish a scalable workflow for the production, separation, purification, radiolabeling, and preclinical assessment of ¹⁰³Pd for theranostic applications. Methods: ¹⁰³Pd was produced via the ¹⁰³Rh(p,n)¹⁰³Pd reaction. An upgraded dry-distillation radionuclide separation equipment (RSE) enabled high-efficiency separation from irradiated rhodium foils, while a cotton-assisted acid recovery process yielded purified ¹⁰³Pd suitable for radiolabeling. Chelation with NOTA and DOTA-TATE was performed, and radiochemical purity was assessed using iTLC, SPE, and a C18 column. In vivo SPECT/CT imaging was conducted in NMRI Nu/Nu mice and in a canine model with spontaneous liver metastatic spread of insulinoma, injected with [¹⁰³Pd]Pd-labeled compounds. Results: The upgraded RSE achieved separation efficiencies of 64–86% and overall recovery yields of 81–94%, outperforming conventional wet-chemistry methods. Radiolabeling produced stable complexes with >95% radiochemical purity. SPECT/CT imaging confirmed in vivo stability in mice. In the canine model, a slight reduction in tumor size and increased glucose levels were observed during 24 days post-systemic application of 520 MBq of ¹⁰³Pd-DOTA-TATE radioactivity. Conclusions: This study establishes a complete and efficient radiochemical and preclinical pipeline for ¹⁰³Pd, demonstrating its feasibility as a theranostic radionuclide. The combination of high-yield production, robust separation chemistry, and localized Auger-mediated energy deposition highlights ¹⁰³Pd as a promising candidate for future targeted radionuclide therapy applications.

An effective, near-infrared (NIR) fluorescent Ca²⁺ sensor, Solomon-red-BAPTA, featuring a dioxothioxanthene moiety was developed for microscopy. A rapid and operationally simple synthetic route is described. The key step involves a room-temperature DDQ-mediated cross-dehydrogenative coupling (CDC) of the fluorescent precursor and BAPTA followed by a one-pot oxidation. The sensor exhibited excellent photophysical characteristics including a 160-fold fluorescence enhancement with excitation and emission maxima at 712 nm and 736 nm, respectively, suggesting high tissue-penetrating capacity. Based on the experimental data, the structure–property relationship was elucidated and further supported by DFT calculations, particularly with respect to the photoinduced electron transfer (PET)-based fluorescence turn-on mechanism.

This paper will present in vivo release profiles of Doxorubicin.HCl from halo-spun drug-loaded rubbery porous mats. For the very first time, Fluorescent Organism Bioimaging (FOBI) was used to follow drug release in a live animal model with induced tumors. A new predictive model based on apparent diffusion coefficients to simulate release profiles will also be presented and could have general applications for release profile predictions. Surprisingly, histological evaluation found that the tissue layer forming next to the drug-eluting mats had unordered morphology and only necrotic cells. This is a stunning contrast to the highly regular collagen structure next to mats without the drug, typical of an adverse foreign body type reaction. The findings suggest that this drug-eluting fiber mat can be used as a local chemotherapy approach coupled with mitigation of capsular contracture, the major complication associated with breast reconstruction following mastectomy.

Magnetic iron oxide nanoparticles are frequently utilized as contrast agents in magnetic resonance imaging (MRI). However, the release of iron ions leads to the formation of reactive oxygen species (ROS), resulting in cell damage. In this study, we developed MRI contrast agents containing amine-functionalized MnFe₂O₄ nanoparticles with a Prussian blue (PB) surface coating to enhance their biocompatibility. The prepared MNPs were embedded in polyvinylpyrrolidone and dried. The resulting crystals can be redispersed in water immediately before use, forming a stable colloid. The particle size of nanoparticles (43 ± 13 nm) is suitable for the intended application. The values of Hc (52 Oe) and Mr (3.7 emu/g) for the particles indicate a soft ferromagnetic nature. The coating of the particles with PB results in a significant reduction of their toxicity, as evidenced by a toxicological test on HEK293 cells. This colloid was tested in vitro as an MRI contrast agent as well as in healthy animal. The longitudinal relaxivity (r₁) of the PB-MnFe₂O₄-NH₂ sample was determined to be 0.01 (mg/mL)⁻¹ms^− 1. The transversal relaxivity was measured as well (r₂: 0.77 (mg/mL)⁻¹ms^− 1 and r₂*: 1.48 (mg/mL)⁻¹ms^− 1, which were in the same range as Feraheme and Endorem. Prussian blue-coated MnFe₂O₄ emerges as a promising T2-weighted contrast material, representing a novel combination of two well-known contrast-capable materials.

Copper ferrite nanoparticles for use as MRI contrast agents were synthesized using two different methods. A novel microwave-assisted (MW) solvothermal method was developed and compared to a conventional 12-hour synthesis (Reflux) as an eco-friendlier approach. This innovative synthesis method successfully produced nanoparticles with enhanced properties compared to traditional ferrite materials. The nanoparticles’ morphological and magnetic properties were evaluated and tested in in-vivo MRI studies. The results revealed both similarities and differences between the amine-functionalized copper ferrite nanoparticles. FTIR, XRD, HRTEM, and VSM analyses indicated improved properties in the CuFe₂O₄-NH₂ MW particles, while AFM confirmed successful polymer encapsulation of the nanoparticles. For the CuFe₂O₄-NH₂ MW sample, 76.8 wt% copper ferrite and 23.2 wt% magnetite were detected, with crystallite sizes of 8 ± 2 nm and 13 ± 2 nm, respectively. In the CuFe₂O₄-NH₂ Refl. sample, in addition to these two magnetic phases, larger copper particles (31.6 wt%) were also formed. DLS analysis demonstrated that the CuFe₂O₄-NH₂ MW sample exhibited excellent colloidal stability, maintaining its size distribution in aqueous media for 3 hours without aggregation, unlike the CuFe₂O₄-NH₂ Refl. sample, which showed slight aggregation. The CuFe₂O₄-NH₂ MW sample displayed superparamagnetic behavior (Ms: 15 emu/g, Mr: 0 emu/g, Hc: 0 Oe), while the CuFe₂O₄-NH₂ Refl. sample exhibited ferromagnetic characteristics (Ms: 40 emu/g, Mr: 1.35 emu/g, Hc: 30 Oe). Both samples produced comparable results during in vitro MRI measurements, showing similar T2* relaxation and signal characteristics. Further in vivo studies demonstrated that both samples induced significant hypointense changes. The study provides valuable insights into the synthesis, properties, and potential applications of these materials, emphasizing the importance of eco-friendly methods and the optimization of ferrite-based 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.

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.

Imaging keeps pervading biomedical sciences from the nanoscale to the bedside. Connecting the hierarchical levels of biomedicine with relevant imaging approaches, however, remains a challenge. Here we present a concept, called “3M”, which can deliver a question, formulated at the bedside, across the wide-ranging hierarchical organization of the living organism, from the molecular level, through the small-animal scale, to whole-body human functional imaging. We present an example of nanoparticle development pipeline extending from atomic force microscopy to pre-clinical whole body imaging methods to highlight the essential features of the 3M concept, which integrates multi-scale resolution and quantification into a single logical process. Using the nanoscale to human clinical whole body approach, we present the successful development, characterisation and application of Prussian Blue nanoparticles for a variety of imaging modalities, extending it to isotope payload quantification and shape-biodistribution relationships. The translation of an idea from the bedside to the molecular level and back requires a set of novel combinatorial imaging methodologies interconnected into a logical pipeline. The proposed integrative molecules-to-mouse-to-man (3M) approach offers a promising, clinically oriented toolkit that lends the prospect of obtaining an ever-increasing amount of correlated information from as small a voxel of the human body as possible.

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.