bims-mricoa Biomed News
on MRI contrast agents
Issue of 2021‒10‒03
nineteen papers selected by
Merve Yavuz
Bilkent University

  1. Int J Mol Sci. 2021 Sep 17. pii: 10071. [Epub ahead of print]22(18):
      Different chemical agents are used for the biocompatibility and/or functionality of the nanoparticles used in magnetic hyperthermia to reduce or even eliminate cellular toxicity and to limit the interaction between them (van der Waals and magnetic dipolar interactions), with highly beneficial effects on the efficiency of magnetic hyperthermia in cancer therapy. In this paper we propose an innovative strategy for the biocompatibility of these nanoparticles using gamma-cyclodextrins (γ-CDs) to decorate the surface of magnetite (Fe3O4) nanoparticles. The influence of the biocompatible organic layer of cyclodextrins, from the surface of Fe3O4 ferrimagnetic nanoparticles, on the maximum specific loss power in superparamagnetic hyperthermia, is presented and analyzed in detail in this paper. Furthermore, our study shows the optimum conditions in which the magnetic nanoparticles covered with gamma-cyclodextrin (Fe3O4-γ-CDs) can be utilized in superparamagnetic hyperthermia for an alternative cancer therapy with higher efficiency in destroying tumoral cells and eliminating cellular toxicity.
    Keywords:  Brown relaxation; Néel magnetic relaxation; alternative cancer therapy; magnetite nanoparticles; maximum specific loss power; superparamagnetic hyperthermia; γ-cyclodextrins
  2. Nat Nanotechnol. 2021 Sep 27.
      Recent advances in molecular engineering and synthetic biology provide biomolecular and cell-based therapies with a high degree of molecular specificity, but limited spatiotemporal control. Here we show that biomolecules and cells can be engineered to deliver potent mechanical effects at specific locations inside the body through ultrasound-induced inertial cavitation. This capability is enabled by gas vesicles, a unique class of genetically encodable air-filled protein nanostructures. We show that low-frequency ultrasound can convert these biomolecules into micrometre-scale cavitating bubbles, unleashing strong local mechanical effects. This enables engineered gas vesicles to serve as remotely actuated cell-killing and tissue-disrupting agents, and allows genetically engineered cells to lyse, release molecular payloads and produce local mechanical damage on command. We demonstrate the capabilities of biomolecular inertial cavitation in vitro, in cellulo and in vivo, including in a mouse model of tumour-homing probiotic therapy.
  3. Nanomaterials (Basel). 2021 Aug 31. pii: 2267. [Epub ahead of print]11(9):
      Magnetic nanoparticles (MNPs) are widely known as valuable agents for biomedical applications. Recently, MNPs were further suggested to be used for a remote and non-invasive manipulation, where their spatial redistribution or force response in a magnetic field provides a fine-tunable stimulus to a cell. Here, we investigated the properties of two different MNPs and assessed their suitability for spatio-mechanical manipulations: semisynthetic magnetoferritin nanoparticles and fully synthetic 'nanoflower'-shaped iron oxide nanoparticles. As well as confirming their monodispersity in terms of structure, surface potential, and magnetic response, we monitored the MNP performance in a living cell environment using fluorescence microscopy and asserted their biocompatibility. We then demonstrated facilitated spatial redistribution of magnetoferritin compared to 'nanoflower'-NPs after microinjection, and a higher magnetic force response of these NPs compared to magnetoferritin inside a cell. Our remote manipulation assays present these tailored magnetic materials as suitable agents for applications in magnetogenetics, biomedicine, or nanomaterial research.
    Keywords:  iron oxide nanoparticles; magnetoferritin; magnetogenetics; remote particle manipulation
  4. Nanomaterials (Basel). 2021 Sep 08. pii: 2337. [Epub ahead of print]11(9):
      In recent years, many promising nanotechnological approaches to biomedical research have been developed in order to increase implementation of regenerative medicine and tissue engineering in clinical practice. In the meantime, the use of nanomaterials for the regeneration of diseased or injured tissues is considered advantageous in most areas of medicine. In particular, for the treatment of cardiovascular, osteochondral and neurological defects, but also for the recovery of functions of other organs such as kidney, liver, pancreas, bladder, urethra and for wound healing, nanomaterials are increasingly being developed that serve as scaffolds, mimic the extracellular matrix and promote adhesion or differentiation of cells. This review focuses on the latest developments in regenerative medicine, in which iron oxide nanoparticles (IONPs) play a crucial role for tissue engineering and cell therapy. IONPs are not only enabling the use of non-invasive observation methods to monitor the therapy, but can also accelerate and enhance regeneration, either thanks to their inherent magnetic properties or by functionalization with bioactive or therapeutic compounds, such as drugs, enzymes and growth factors. In addition, the presence of magnetic fields can direct IONP-labeled cells specifically to the site of action or induce cell differentiation into a specific cell type through mechanotransduction.
    Keywords:  SPION; magnetic drug delivery; magnetic particles; magnetic resonance imaging; nanomedicine; superparamagnetic iron oxide nanoparticles
  5. Nanomaterials (Basel). 2021 Sep 20. pii: 2449. [Epub ahead of print]11(9):
      Gadolinium (Gd) based contrast agents (CAs) (Gd-CAs) represent one of the most advanced developments in the application of Gd for magnetic resonance imaging (MRI). Current challenges with existing CAs generated an urgent requirement to develop multimodal CAs with good biocompatibility, low toxicity, and prolonged circulation time. This review discussed the Gd-CAs used in bioimaging applications, addressing their advantages and limitations. Future research is required to establish the safety, efficacy and theragnostic capabilities of Gd-CAs. Nevertheless, these Gd-CAs offer extraordinary potential as imaging CAs and promise to benefit bioimaging applications significantly.
    Keywords:  bio-imaging applications; coating ligands; gadolinium based contrast agents; gadolinium oxide nanoparticles; magnetic resonance imaging; nanoparticles
  6. Nanomaterials (Basel). 2021 Aug 25. pii: 2179. [Epub ahead of print]11(9):
      The ability of magnetic nanoparticles (MNPs) to transform electromagnetic energy into heat is widely exploited in well-known thermal cancer therapies, such as magnetic hyperthermia, which proves useful in enhancing the radio- and chemo-sensitivity of human tumor cells. Since the heat release is ruled by the complex magnetic behavior of MNPs, a careful investigation is needed to understand the role of their intrinsic (composition, size and shape) and collective (aggregation state) properties. Here, the influence of geometrical parameters and aggregation on the specific loss power (SLP) is analyzed through in-depth structural, morphological, magnetic and thermometric characterizations supported by micromagnetic and heat transfer simulations. To this aim, different samples of cubic Fe3O4 NPs with an average size between 15 nm and 160 nm are prepared via hydrothermal route. For the analyzed samples, the magnetic behavior and heating properties result to be basically determined by the magnetic single- or multi-domain configuration and by the competition between magnetocrystalline and shape anisotropies. This is clarified by micromagnetic simulations, which enable us to also elucidate the role of magnetostatic interactions associated with locally strong aggregation.
    Keywords:  chemical synthesis; iron oxide nanocubes; magnetic hyperthermia; magnetic nanoparticles; magnetometry; micromagnetic simulations; nanomedicine; thermal simulations; thermometric measurements
  7. Microorganisms. 2021 Aug 31. pii: 1854. [Epub ahead of print]9(9):
      In this study, the magnetic properties of magnetosomes isolated from lyophilized magnetotactic bacteria Magnetospirillum caucaseum SO-1 were assessed for the first time. The shape and size of magnetosomes and cell fragments were studied by electron microscopy and dynamic light scattering techniques. Phase and elemental composition were analyzed by X-ray and electron diffraction and Raman spectroscopy. Magnetic properties were studied using vibrating sample magnetometry and electron paramagnetic resonance spectroscopy. Theoretical analysis of the magnetic properties was carried out using the model of clusters of magnetostatically interacting two-phase particles and a modified method of moments for a system of dipole-dipole-interacting uniaxial particles. Magnetic properties were controlled mostly by random aggregates of magnetosomes, with a minor contribution from preserved magnetosome chains. Results confirmed the high chemical stability and homogeneity of bacterial magnetosomes in comparison to synthetic iron oxide magnetic nanoparticles.
    Keywords:  Magnetospirillum caucaseum SO-1; bacterial magnetosomes; magnetic properties; magnetostatic interaction; magnetotactic bacteria; theoretical modeling
  8. Nanomaterials (Basel). 2021 Aug 26. pii: 2197. [Epub ahead of print]11(9):
      This study aimed to systematically understand the magnetic properties of magnetite (Fe3O4) nanoparticles functionalized with different Pluronic F-127 surfactant concentrations (Fe3O4@Pluronic F-127) obtained by using an improved magnetic characterization method based on three-dimensional magnetic maps generated by scanning magnetic microscopy. Additionally, these Fe3O4 and Fe3O4@Pluronic F-127 nanoparticles, as promising systems for biomedical applications, were prepared by a wet chemical reaction. The magnetization curve was obtained through these three-dimensional maps, confirming that both Fe3O4 and Fe3O4@Pluronic F-127 nanoparticles have a superparamagnetic behavior. The as-prepared samples, stored at approximately 20 °C, showed no change in the magnetization curve even months after their generation, resulting in no nanoparticles free from oxidation, as Raman measurements have confirmed. Furthermore, by applying this magnetic technique, it was possible to estimate that the nanoparticles' magnetic core diameter was about 5 nm. Our results were confirmed by comparison with other techniques, namely as transmission electron microscopy imaging and diffraction together with Raman spectroscopy. Finally, these results, in addition to validating scanning magnetic microscopy, also highlight its potential for a detailed magnetic characterization of nanoparticles.
    Keywords:  Pluronic F-127; co-precipitation; magnetic nanoparticles; scanning magnetic microscope
  9. Protein Cell. 2021 Sep 29.
      Cell therapy approaches that employ engineered mammalian cells for on-demand production of therapeutic agents in the patient's body are moving beyond proof-of-concept in translational medicine. The therapeutic cells can be customized to sense user-defined signals, process them, and respond in a programmable and predictable way. In this paper, we introduce the available tools and strategies employed to design therapeutic cells. Then, various approaches to control cell behaviors, including open-loop and closed-loop systems, are discussed. We also highlight therapeutic applications of engineered cells for early diagnosis and treatment of various diseases in the clinic and in experimental disease models. Finally, we consider emerging technologies such as digital devices and their potential for incorporation into future cell-based therapies.
    Keywords:  cell engineering; cell-based therapy; controllable genetic circuits; synthetic biology; therapeutic gene expression
  10. Adv Mater. 2021 Sep 29. e2103114
      Bifunctional proteins (BFPs) are a class of therapeutic agents produced through genetic engineering and protein engineering, and are increasingly used to treat various human diseases, including cancer. These proteins usually have two or more biological functions-specifically recognizing different molecular targets to regulate the related signaling pathways, or mediating effector molecules/cells to kill tumor cells. Unlike conventional small-molecule or single-target drugs, BFPs possess stronger biological activity but lower systemic toxicity. Hence, BFPs are considered to offer many benefits for the treatment of heterogeneous tumors. In this review, the authors briefly describe the unique structural feature of BFP molecules and innovatively divide them into bispecific antibodies, cytokine-based BFPs (immunocytokines), and protein toxin-based BFPs (immunotoxins) according to their mode of action. In addition, the latest advances in the development of BFPs are discussed and the potential limitations or problems in clinical applications are outlined. Taken together, future studies need to be centered on understanding the characteristics of BFPs for optimizing and designing more effective such drugs.
    Keywords:  bifunctional proteins; classifications; clinical applications; effector molecules; targeted deliveries
  11. Cancers (Basel). 2021 Sep 12. pii: 4583. [Epub ahead of print]13(18):
      Hyperthermia has emerged as a promising alternative to conventional cancer therapies and in fact, traditional hyperthermia is now commonly used in combination with chemotherapy or surgery during cancer treatment. Nevertheless, non-specific application of hyperthermia generates various undesirable side-effects, such that nano-magnetic hyperthermia has arisen a possible solution to this problem. This technique to induce hyperthermia is based on the intrinsic capacity of magnetic nanoparticles to accumulate in a given target area and to respond to alternating magnetic fields (AMFs) by releasing heat, based on different principles of physics. Unfortunately, the clinical implementation of nano-magnetic hyperthermia has not been fluid and few clinical trials have been carried out. In this review, we want to demonstrate the need for more systematic and basic research in this area, as many of the sub-cellular and molecular mechanisms associated with this approach remain unclear. As such, we shall consider here the biological effects that occur and why this theoretically well-designed nano-system fails in physiological conditions. Moreover, we will offer some guidelines that may help establish successful strategies through the rational design of magnetic nanoparticles for magnetic hyperthermia.
    Keywords:  clinical trial; hyperthermia; magnetic hyperthermia; magnetic nanoparticle-induced biological effects; magnetic nanoparticles; new therapies
  12. Nanoscale. 2021 Sep 27.
      Despite the high level of interest in bio-nano interactions, detailed intracellular mechanisms that govern nanoscale recognition and signalling still need to be unravelled. Magnetic nanoparticles (NPs) are valuable tools for elucidating complex intracellular bio-nano interactions. Using magnetic NPs, it is possible to isolate cell compartments that the particles interact with during intracellular trafficking. Studies at the subcellular scale rely heavily on optical microscopy; therefore, combining the advantages of magnetic recovery with excellent imaging properties to allow intracellular NP tracking is of utmost interest for the nanoscience field. However, it is a challenge to prepare highly magnetic NPs with a suitable fluorescence for the fluorescence imaging techniques typically used for biological studies. Here we present the synthesis of biocompatible multifunctional superparamagnetic multicore NPs with a bright fluorescent silica shell. The incorporation of an organic fluorophore in the silica surrounding the magnetic multicore was optimised to enable the particles to be tracked with the most common imaging techniques. To prevent dye loss resulting from silica dissolution in biological environments, which would reduce the time that the particles could be tracked, we added a thin dense encapsulating silica layer to the NPs which is highly stable in biological media. The synthesised multifunctional nanoparticles were evaluated in cell uptake experiments in which their intracellular location could be clearly identified using fluorescence imaging microscopy, even after 3 days. The magnetic properties of the iron oxide core enabled both efficient recovery of the NPs from the intracellular environment and the extraction of cell compartments involved in their intracellular trafficking. Thus, the NPs reported here provide a promising tool for the study of the processes regulating bio-nano interactions.
  13. Biomed Microdevices. 2021 Oct 01. 23(4): 52
      In contrast to traditional large-scale robots, which require complicated mechanical joints and material rigidity, microrobots made of soft materials have exhibited amazing features and great potential for extensive applications, such as minimally invasive surgery. However, microrobots are faced with energy supply and control issues due to the miniaturization. Magnetic field actuation emerges as an appropriate approach to tackle with these issues. This review summarizes the latest progress of biomimetic soft microrobots actuated by magnetic field. Starting with an overview of the soft material and magnetic material adopted in the magnetic field actuated soft microrobots, the various fabrication methods and design structures of soft microrobots are summarized. Subsequently, practical and potential applications, such as targeted therapy, surgical operation, and the transportation of microscopic objects, in the fields of biomedicine and environmental remediation are presented. In the end, some current challenges, and the future development trends of magnetic soft microrobots are briefly discussed. This review is expected to offer a helpful guidance for the new researchers of biomimetic soft microrobots actuated by magnetic field.
    Keywords:  Bioinspired; Magnetic field; Soft microrobot
  14. Nanomaterials (Basel). 2021 Aug 25. pii: 2184. [Epub ahead of print]11(9):
      The in vivo distribution of 50 nm clusters of polyethylene glycol-conjugated superparamagnetic iron oxide nanoparticles (SPIONs-PEG) was conducted in this study. SPIONs-PEG were synthesized de novo, and their structure and paramagnetic behaviors were analyzed by specific methods (TEM, DLS, XRD, VSM). Wistar rats were treated with 10 mg Fe/kg body weight SPIONs-PEG and their organs and blood were examined at two intervals for short-term (15, 30, 60, 180 min) and long-term (6, 12, 24 h) exposure evaluation. Most exposed organs were investigated through light and transmission electron microscopy, and blood and urine samples were examined through fluorescence spectrophotometry. SPIONs-PEG clusters entered the bloodstream after intraperitoneal and intravenous administrations and ended up in the urine, with the highest clearance at 12 h. The skin and spleen were within normal histological parameters, while the liver, kidney, brain, and lungs showed signs of transient local anoxia or other transient pathological affections. This study shows that once internalized, the synthesized SPIONs-PEG disperse well through the bloodstream with minor to nil induced tissue damage, are biocompatible, have good clearance, and are suited for biomedical applications.
    Keywords:  SPIONs-PEG; electron microscopy; in vivo tracking; liver; lung; magnetic nanoparticles
  15. Colloids Surf B Biointerfaces. 2021 Sep 20. pii: S0927-7765(21)00567-1. [Epub ahead of print]208 112123
      The capability of HeLa cells to internalize large spherical microparticles has been evaluated by using inorganic, magnetic microparticles of 1 and 2.8 µm of diameter. In both absence but especially under the action of a magnet, both types of particles were uptaken, in absence of cytotoxicity, by a significant percentage of cells, in a non-endosomal process clearly favored by the magnetic field. The engulfed particles efficiently drive inside the cells chemically associated proteins such as GFP and human alpha-galactosidase A, without any apparent loss of protein functionalities. While 1 µm particles are completely engulfed, at least a fraction of 2.8 µm particles remain embedded into the cell membrane, with only a fraction of their surface in cytoplasmic contact. The detected tolerance to endosomal-independent cell penetration of microscale objects is not then restricted to organic, soft materials (such as bacterial inclusion bodies) as previously described, but it is a more general phenomenon also applicable to inorganic materials. In this scenario, the use of magnetic particles in combination with external magnetic fields can represent a significant improvement in the internalization efficiency of such agents optimized as drug carriers. This fact offers a wide potential in the design and engineering of novel particulate vehicles for therapeutic, diagnostic and theragnostic applications.
    Keywords:  Cell penetration; Cellular therapy; Human alpha-galactosidase A; Magnetic particles; Recombinant protein
  16. Radiol Technol. 2021 Sep;93(1): 36-45
      PURPOSE: To evaluate peer-reviewed research to determine whether modern manganese-based contrast agents offer a safe and effective alternative to gadolinium.METHODS: Searches of 3 academic databases transpired in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Exclusion and inclusion criteria were applied to determine the final article selection.
    RESULTS: Eighteen articles met the inclusion criteria for the systematic review, comprising 7 categories of manganese-based imaging probes based on chelating molecules and molecular structure.
    DISCUSSION: Although researchers discussed the effects of the imaging probes on T1 contrast in every selected study, safety information was much sparser. With rare exception, the manganese-based contrast agents met or exceeded marks for imaging efficacy, and when researchers studied safety, most probes offered promising results. The implications of these findings provide future health care researchers an opportunity to compare the proposed probes to each other as well as gadolinium, create consistent protocols for testing manganese-based contrast agents, and thoroughly evaluate their safety.
    CONCLUSION: Manganese-based contrast agents have the potential to replace gadolinium-based imaging probes in terms of pathology visualization, but researchers have yet to address safety adequately.
    Keywords:  MRI; contrast agent; gadolinium; magnetic resonance imaging; manganese
  17. Nanoscale. 2021 Oct 01. 13(37): 15631-15646
      The use of magnetic nanoparticles (MNPs) to locally increase the temperature at the nanoscale under the remote application of alternating magnetic fields (magnetic particle hyperthermia, MHT) has become an important subject of nanomedicine multidisciplinary research, focusing among other topics on the optimization of the heating performance of MNPs and their assemblies under the effect of the magnetic field. We report experimental data of heat released by MNPs using a wide range of anisometric shapes and their assemblies in different media. We outline a basic theoretical investigation, which assists the interpretation of the experimental data, including the effect of the size, shape and assembly of MNPs on the MNPs' hysteresis loops and the maximum heat delivered. We report heat release data of anisometric MNPs, including nanodisks, spindles (elongated nanoparticles) and nanocubes, analysing, for a given shape, the size dependence. We study the MNPs either acting as individuals or assembled through a magnetic-field-assisted method. Thus, the physical geometrical arrangement of these anisometric particles, the magnetization switching and the heat release (by means of the determination of the specific adsorption rate, SAR values) under the application of AC fields have been analysed and compared in aqueous suspensions and after immobilization in agar matrix mimicking the tumour environment. The different nano-systems were analysed when dispersed at random or in assembled configurations. We report a systematic fall in the SAR for all anisometric MNPs randomly embedded in a viscous environment. However, certain anisometric shapes will have a less marked, an almost total preservation or even an increase in SAR when embedded in a viscous environment with certain orientation, in contrast to the measurements in water solution. Discrepancies between theoretical and experimental values reflect the complexity of the systems due to the interplay of different factors such as size, shape and nanoparticle assembly due to magnetic interactions. We demonstrate that magnetic assembly holds great potential for producing materials with high functional and structural diversity, as we transform our nanoscale building blocks (anisometric MNPs) into a material displaying enhanced SAR properties.
  18. Cells. 2021 Sep 17. pii: 2462. [Epub ahead of print]10(9):
      Ferroptosis is a regulated form of cell death characterized by iron dependency and increased lipid peroxidation. Initially assumed to be selectively induced in tumour cells, there is increasing evidence that ferroptosis plays an important role in pathophysiology and numerous cell types and tissues. Deregulated ferroptosis has been linked to human diseases, such as neurodegenerative diseases, cardiovascular disorders, and cancer. Along these lines, ferroptosis is a promising pathway to overcoming therapy resistance of cancer cells. It is therefore of utmost importance to understand the cellular signalling pathways and the molecular mechanisms underlying ferroptosis regulation, including context-specific effects mediated by the neighbouring cells through cell-cell contacts. Here, we give an overview on the molecular events and machinery linked to ferroptosis induction and commitment. We further summarize and discuss current knowledge about the role of cell-cell contacts, which differ in ferroptosis regulation between normal somatic cells and cancer cells. We present emerging concepts on the underlying mechanisms, address open questions, and discuss the possible impact of cell-cell contacts on exploiting ferroptosis in cancer therapy.
    Keywords:  cancer therapy; cell–cell contacts; epithelial–mesenchymal transition; ferroptosis
  19. Front Cell Dev Biol. 2021 ;9 733751
      Cell death induction has become popular as a novel cancer treatment. Ferroptosis, a newly discovered form of cell death, features regulated, iron-dependent accumulation of lipid hydroperoxides. Since this word "ferroptosis" was coined, numerous studies have examined the complex relationship between ferroptosis and cancer. Here, starting from the intrinsic hallmarks of cancer and cell death, we discuss the theoretical basis of cell death induction as a cancer treatment. We review various aspects of the relationship between ferroptosis and cancer, including the genetic basis, epigenetic modification, cancer stem cells, and the tumor microenvironment, to provide information and support for further research on ferroptosis. We also note that exosomes can be applied in ferroptosis-based therapy. These extracellular vesicles can deliver different molecules to modulate cancer cells and cell death pathways. Using exosomes to control ferroptosis occurring in targeted cells is promising for cancer therapy.
    Keywords:  apoptosis; cancer; cell death; exosomes; ferroptosis