The interest in hybrid nanoparticles for various applications in biomedicine is growing inevitably, stimulating research towards not only more effective, but also more accessible systems. This resulted in the emergence of advanced synthetic protocols with optimized conditions for the production of nanoparticles with high yields and desired morphologies, which ultimately determine their physicochemical and biomedical properties. While these challenges were sufficient for scientists a few decades ago, the sustainability of the synthetic methods is now an important aspect. From this perspective, nanoparticle production methods based on physical principles, such as spark discharge phenomena, could provide an interesting alternative to labor-intensive and environmentally harmful chemical synthesis. The benefits of clean and sustainable physical production routes for various nanomaterials are already recognized in the fields of catalysis and electronics. Biomedicine on the other hand has been reluctant to embrace the new methodologies, as they do not inherently provide nanoparticles dispersed in aqueous media, which is essential for their safe administration and reliable physiological performance. In this work, we investigated the potential of spark discharge as an alternative method to produce hybrid palladium/iron oxide nanoparticles intended for cancer thermo-brachytherapy by leveraging the magnetothermal properties of iron and the favorable radioactive features of the palladium radioisotope. Focusing on the aqueous harvesting of the nanoparticles produced in VSParticle’s spark discharge generator, we determined the optimal settings compatible with the connected bubbling column and identified the pitfalls and possible solutions to the intrinsic challenges, such as low yields and aggregation.

Objective: To investigate the potential of hybrid Pd/Fe-oxide magnetic nanoparticles designed for thermo-brachytherapy of breast cancer, considering their specific loss power (SLP) and clinical constraints in the applied magnetic field. Methods: Hybrid nanoparticles consisting of palladium-core and iron oxide shell of increasing thickness, were suspended in water and their SLPs were measured at varying magnetic fields (12–26 mT peak) and frequencies (50–730 kHz) with a commercial alternating magnetic field generator (magneTherm™ Digital, nanoTherics Ltd.). Results: Validation of the heating device used in this study with commercial HyperMag-C nanoparticles showed a small deviation (±4%) over a period of 1 year, confirming the reliability of the method. The integration of dual thermometers, one in the center and one at the bottom of the sample vial, allowed monitoring of homogeneity of the sample suspensions. SLPs measurements on a series of nanoparticles of increasing sizes showed the highest heating for the diameter of 21 nm (SLP = 225 W/g) at the applied frequencies of 346 and 730 kHz. No heating was observed for the nanoparticles with the size <14 nm, confirming the importance of the size-parameter. The heating ability of the best performing Pd/Fe-oxide-21 was calculated to be sufficient to ablate tumors with a radius ±4 and 12 mm using 10 and 1 mg/mL nanoparticle concentration, respectively. Conclusions: Nanoparticles consisting of non-magnetic palladium-core and magnetic iron oxide shell are suitable for magnetic hyperthermia/thermal ablation under clinically safe conditions of 346 kHz and 19.1 mT, with minimal eddy current effects in combination with maximum SLP.

While hyperthermia has been shown to induce a variety of cytotoxic and sensitizing effects on cancer tissues, the thermal dose–effect relationship is still not well quantified, and it is still unclear how it can be optimally combined with other treatment modalities. Additionally, it is speculated that different methods of applying hyperthermia, such as water bath heating or electromagnetic energy, may have an effect on the resulting biological mechanisms involved in cell death or in sensitizing tumor cells to other oncological treatments. In order to further quantify and characterize hyperthermia treatments on a cellular level, in vitro experiments shifted towards the use of 3D cell spheroids. These are in fact considered a more representative model of the cell environment when compared to 2D cell cultures. In order to perform radiofrequency (RF)-induced heating in vitro, we have recently developed a dedicated electromagnetic field applicator. In this study, using this applicator, we designed and validated an experimental setup which can heat 3D cell spheroids in a conical polypropylene vial, thus providing a reliable instrument for investigating hyperthermia effects at the cellular scale.

In this review, the chemical mechanisms behind the interactions between boronic acids and N-acetylneuraminic acids, which have been widely utilized in biomedicine in recent decades, will be examined. It will also be highlighted that the affinity of boronic acids for N-acetylneuraminic acids is dependent on pH and is complementary to their affinity for other common monosaccharides found in glycocalyces. Through various examples from the literature, the unique pH profile of the boronic – N-acetylneuraminic acids acid interaction and its uses in biomedicine will be illustrated.

Porous materials, such as zeolites, have great potential for biomedical applications, thanks to their ability to accommodate positively charged metal-ions and their facile surface functionalization. Although the latter aspect is important to endow the nanoparticles with chemical/colloidal stability and desired biological properties, the possibility for simple ion-exchange enables easy switching between imaging modalities and/or combination with therapy, depending on the envisioned application. In this study, the nanozeolite Linde type L (LTL) with already confirmed magnetic resonance imaging properties, generated by the paramagnetic gadolinium (GdIII) in the inner cavities, was successfully radiolabeled with a positron emission tomography (PET)-tracer zirconium-89 (89Zr). Thereby, exploiting 89Zr-chloride resulted in a slightly higher radiolabeling in the inner cavities compared to the commonly used 89Zr-oxalate, which apparently remained on the surface of LTL. Intravenous injection of PEGylated 89Zr/GdIII-LTL in healthy mice allowed for PET-computed tomography evaluation, revealing initial lung uptake followed by gradual migration of LTL to the liver and spleen. Ex vivo biodistribution confirmed the in vivo stability and integrity of the proposed multimodal probe by demonstrating the original metal/Si ratio being preserved in the organs. These findings reveal beneficial biological behavior of the nanozeolite LTL and hence open the door for follow-up theranostic studies by exploiting the immense variety of metal-based radioisotopes.

Designing novel systems for efficient cancer treatment and improving the quality of life for patients is a prime requirement in the healthcare sector. In this regard, theranostics have recently emerged as a unique platform, which combines the benefits of both diagnosis and therapeutics delivery. Theranostics have the desired contrast agent and the drugs combined in a single carrier, thus providing the opportunity for real-time imaging to monitor the therapy results. This helps in reducing the hazards related to treatment overdose or underdose and gives the possibility of personalized therapy. Polysaccharides, as natural biomolecules, have been widely explored to develop theranostics, as they act as a matrix for simultaneously loading both contrast agents and drugs for their utility in drug delivery and imaging. Additionally, their remarkable physicochemical attributes (biodegradability, satisfactory safety profile, abundance, and diversity in functionality and charge) can be tuned via postmodification, which offers numerous possibilities to develop theranostics with desired characteristics. Hence, we provide an overview of recent advances in polysaccharide matrix-based theranostics for drug delivery combined with magnetic resonance imaging, computed tomography, positron emission tomography, single photon emission computed tomography, and ultrasound imaging. Herein, we also summarize the toxicity assessment of polysaccharides, associated contrast agents, and nanotoxicity along with the challenges and future research directions.

This study presents a series of light-harvesting materials, where multiple chromophores are organised into host-guest silica-micelle structures at specific locations by means of self-assembly strategies. Binary and ternary mesoscopic antennae were realized, using organometallic complexes and organic dyes as energy transfer units and varying their content and localization to manipulate transfer rate and efficiency inside the materials. Steady-state and time-resolved UV–vis spectroscopy revealed that the three-dye systems show excitation energy cascade from intramicellar dyes to a silica-grafted acceptor, with transfer efficiencies of 20–24 % per step and overall light emission spanning the whole visible range. The two-dye system reaches analogous panchromatic response, featuring almost-white light emission and 47 % efficient transfer, by exploiting the blue-green dual emission of a metallosurfactant as energy donor inside the micellar template and the red emission of a rhodamine acceptor on the silica framework. Both systems show that control over the donor-acceptor distances can be achieved to a certain extent in complex mesoscopic materials and that a vast potential is available for transfer and colour tuning, and specific use of the materials as solid-state sensitisers.

It is known that phenylboronic acid (PBA) can target tumor tissues by binding to sialic acid, a substrate overexpressed by cancer cells. This capability has previously been explored in the design of targeting diagnostic probes such as Gd- and 68Ga-DOTA-EN-PBA, two contrast agents for magnetic resonance imaging (MRI) and positron emission tomography (PET), respectively, whose potential has already been demonstrated through in vivo experiments. In addition to its high resolution, the intrinsic low sensitivity of MRI stimulates the search for more effective contrast agents, which, in the case of small-molecular probes, basically narrows down to either increased tumbling time of the entire molecule or elevated local concentration of the paramagnetic ions, both strategies resulting in enhanced relaxivity, and consequently, a higher MRI contrast. The latter strategy can be achieved by the design of multimeric GdIII complexes. Based on the monomeric PBA-containing probes described recently, herein, we report the synthesis and characterization of the dimeric analogues (GdIII-DOTA-EN)2-PBA and (GdIII-DOTA-EN)2F2PBA. The presence of two Gd ions in one molecule clearly contributes to the improved biological performance, as demonstrated by the relaxometric study and cell-binding investigations.

Mesoporous materials are of vital importance for use in separation, adsorption, and catalysis. The first step in their preparation consists of synthesizing an organic-inorganic hybrid in which a structuring directing agent (SDA, normally a surfactant) is used to provide the desired porosity. The most common method to eliminate the SDA, and generate the porosity, is high-Temperature calcination. Such a process is energy-intensive and slow. In this study, we investigated alternative nonthermal surfactant removal methods on a soft MCM-41 material, aiming at reducing the processing time and temperature, while maximizing the material's properties. The choice of a soft MCM-41 is critical since it is hydrothermally unstable, whereas the SDA removal is troublesome. Microwave processing yielded outstanding performance in terms of surfactant removal, structural preservation, and textural features; the surfactant was fully removed, the hexagonal structure was preserved, and the surface was highly rich in Si-OH groups. It is suggested that H2O2 is the dominant oxidant. In terms of the process features, the processing time is significantly reduced, 14 h (calcination) versus 5 min (microwaves), and the applied temperature is much lower. The energy savings were estimated to be 72% lower as compared to calcination; therefore, this approach contributes to the process intensification of a very relevant material's production.

It is well-known that energy-rich radiation induces water splitting, eventually yielding hydrogen peroxide. Synthetic applications, however, are scarce and to the best of our knowledge, the combination of radioactivity with enzyme-catalysis has not been considered yet. Peroxygenases utilize H2O2 as an oxidant to promote highly selective oxyfunctionalization reactions but are also irreversibly inactivated in the presence of too high H2O2 concentrations. Therefore, there is a need for efficient in situ H2O2 generation methods. Here, we show that radiolytic water splitting can be used to promote specific biocatalytic oxyfunctionalization reactions. Parameters influencing the efficiency of the reaction and current limitations are shown. Particularly, oxidative inactivation of the biocatalyst by hydroxyl radicals influences the robustness of the overall reaction. Radical scavengers can alleviate this issue, but eventually, physical separation of the enzymes from the ionizing radiation will be necessary to achieve robust reaction schemes. We demonstrate that nuclear waste can also be used to drive selective, peroxygenase-catalyzed oxyfunctionalization reactions, challenging our view on nuclear waste in terms of sustainability.

In the periodical system, the lanthanides (the 15 elements in the periodic table between barium and hafnium) are unique in the sense that their trivalent cations have their valence electrons hidden behind the 5s and 5p electrons. They show a gradual decrease in ionic radius with increasing atomic number (also known as the lanthanide contraction). The resulting steric effects determine to a large extent the geometries of complexes of these ions. Here, we discuss these effects, particularly upon the properties of the complexes in aqueous solution, for selected families of Ln³⁺-complexes of oxycarboxylate and aminocarboxylate ligands. The physical properties of the cations are very different, which is very useful for the elucidation of the configuration, conformation and the dynamics of the complexes by X-ray techniques, NMR spectroscopy, and optical techniques. Often the structural analysis is assisted by computational methods.

Paramagnetic macrocycles functionalized with phenylboronic moieties have proven to be interesting for MRI applications based on their ability to recognize cancer cells and generate local contrast. However, full use of the potential of this class of compounds is hampered by laborious and inefficient synthetic and, especially, purification procedures. The amphiphilic character of water-soluble phenylboronates renders them difficult compounds to be prepared through conventional solution synthesis due to the tendency to aggregate and form adducts with other nucleophiles. The new strategy described herein exploits the advantage of solid-phase synthesis with the application of DEAM-PS resin for anchorage and the subsequent simplified derivatization of boronates. GdDOTA-EN-PBA and its fluorinated analogue GdDOTA-EN-F2PBA were synthesized in a much easier, faster and economically convenient way to achieve good yields and purity. Furthermore, the effect of electron-withdrawing fluorine atoms on the aromatic ring of the latter compound was investigated by comparing the physico-chemical properties of both compounds as well as their binding affinity towards melanoma cancer cells.

Radiation therapy has made tremendous progress in oncology over the last decades due to advances in engineering and physical sciences in combination with better biochemical, genetic and molecular understanding of this disease. Local delivery of optimal radiation dose to a tumor, while sparing healthy surrounding tissues, remains a great challenge, especially in the proximity of vital organs. Therefore, imaging plays a key role in tumor staging, accurate target volume delineation, assessment of individual radiation resistance and even personalized dose prescription. From this point of view, radiotherapy might be one of the few therapeutic modalities that relies entirely on high-resolution imaging. Magnetic resonance imaging (MRI) with its superior soft-tissue resolution is already used in radiotherapy treatment planning complementing conventional computed tomography (CT). Development of systems integrating MRI and linear accelerators opens possibilities for simultaneous imaging and therapy, which in turn, generates the need for imaging probeswith therapeutic components. In this review, we discuss the role of MRI in both external and internal radiotherapy focusing on the most important examples of contrast agents with combined therapeutic potential.

Purpose: The aim of this study was to demonstrate the potential of Ga-68-labeled macrocycle (DOTA-en-pba) conjugated with phenylboronic vector for tumor recognition by positron emission tomography (PET), based on targeting of the overexpressed sialic acid (Sia). Procedures: The imaging reporter DOTA-en-pba was synthesized and labeled with Ga-68 at high efficiency. Cell binding assay on Mel-C and B16-F10 melanoma cells was used to evaluate melanin production and Sia overexpression to determine the best model for demonstrating the capability of [⁶⁸Ga]DOTA-en-pba to recognize tumors. The in vivo PET imaging was done with B16-F10 tumor-bearing SCID mice injected with [⁶⁸Ga]DOTA-en-pba intravenously. Tumor, blood, and urine metabolites were assessed to evaluate the presence of a targeting agent. Results: The affinity of [⁶⁸Ga]DOTA-en-pba to Sia was demonstrated on B16-F10 melanoma cells, after the production of melanin as well as Sia overexpression was proved to be up to four times higher in this cell line compared to that in Mel-C cells. Biodistribution studies in B16-F10 tumor-bearing SCID mice showed blood clearance at the time points studied, while uptake in the tumor peaked at 60 min post-injection (6.36 ± 2.41 % ID/g). The acquired PET images were in accordance with the ex vivo biodistribution results. Metabolite assessment on tumor, blood, and urine samples showed that [⁶⁸Ga]DOTA-en-pba remains unmetabolized up to at least 60 min post-injection. Conclusions: Our work is the first attempt for in vivo imaging of cancer by targeting overexpression of sialic acid on cancer cells with a radiotracer in PET.