bims-mricoa Biomed News
on MRI contrast agents
Issue of 2021‒08‒29
eleven papers selected by
Merve Yavuz
Bilkent University

  1. Nanomaterials (Basel). 2021 Jul 29. pii: 1950. [Epub ahead of print]11(8):
      Starting from the mid-1990s, several iron oxide nanoparticles (NPs) were developed as MRI contrast agents. Since their sizes fall in the tenths of a nanometer range, after i.v. injection these NPs are preferentially captured by the reticuloendothelial system of the liver. They have therefore been proposed as liver-specific contrast agents. Even though their unfavorable cost/benefit ratio has led to their withdrawal from the market, innovative applications have recently prompted a renewal of interest in these NPs. One important and innovative application is as diagnostic agents in cancer immunotherapy, thanks to their ability to track tumor-associated macrophages (TAMs) in vivo. It is worth noting that iron oxide NPs may also have a therapeutic role, given their ability to alter macrophage polarization. This review is devoted to the most recent advances in applications of iron oxide NPs in tumor diagnosis and therapy. The intrinsic therapeutic effect of these NPs on tumor growth, their capability to alter macrophage polarization and their diagnostic potential are examined. Innovative strategies for NP-based drug delivery in tumors (e.g., magnetic resonance targeting) will also be described. Finally, the review looks at their role as tracers for innovative, and very promising, imaging techniques (magnetic particle imaging-MPI).
    Keywords:  immunotherapy; iron oxide nanoparticles; magnetic particle imaging; magnetic resonance imaging
  2. Pharmaceutics. 2021 Aug 16. pii: 1262. [Epub ahead of print]13(8):
      Superparamagnetic iron oxide nanoparticles (SPIONs) have been widely used for medicine, both in therapy and diagnosis. Their guided assembly into anisotropic structures, such as nanochains, has recently opened new research avenues; for instance, targeted drug delivery. Interestingly, magnetic nanochains do occur in nature, and they are thought to be involved in the navigation and geographic orientation of a variety of animals and bacteria, although many open questions on their formation and functioning remain. In this review, we will analyze what is known about the natural formation of magnetic nanochains, as well as the synthetic protocols to produce them in the laboratory, to conclude with an overview of medical applications and an outlook on future opportunities in this exciting research field.
    Keywords:  biocompass; biomineralization; magnetic assembly; magnetic navigation; magnetite; magnetoreception; magnetosome chains; magnetotactic bacteria; single domain particles; superparamagnetic iron oxide nanoparticles
  3. Biomed Eng Lett. 2021 Aug 19. 1-11
      Rapid and sensitive detection of pathogenic bacteria in various samples, including food and drinking water, is important to prevent bacterial diseases. Most bacterial solutions contain only a small number of bacteria in complex matrices with impurities; hence, pretreatment is necessary to separate and concentrate target bacteria before sensing. Among various pretreatment methods, iron oxide magnetic nanoparticle (MNP)-based pretreatment has drawn attention owing to the unique properties of MNP, such as high magnetic susceptibility, superparamagnetism, and biocompatibility. After target bacteria are captured by recognition molecule-functionalized MNPs, bacteria-MNP complexes can be easily separated and enriched by applying an external magnetic field. Various devices, such as optical, electrochemical, and magnetoresistance sensors, can be used to detect target bacteria, and their detection principles have been discussed in numerous review papers. Herein, we focus on recent research advances and challenges in magnetic pretreatment of pathogenic bacteria using microfluidic devices, which offer the advantages of process automation and miniaturization.
    Keywords:  Magnetic nanoparticles; Microfluidic; Pathogenic bacteria; Pretreatment
  4. Int J Mol Sci. 2021 Aug 18. pii: 8895. [Epub ahead of print]22(16):
      In magnetic hyperthermia, magnetic nanoparticles (MNPs) are used to generate heat in an alternating magnetic field to destroy cancerous cells. This field can be continuous or pulsed. Although a large amount of research has been devoted to studying the efficiency and side effects of continuous fields, little attention has been paid to the use of pulsed fields. In this simulation study, Fourier's law and COMSOL software have been utilized to identify the heating power necessary for treating breast cancer under blood flow and metabolism to obtain the optimized condition among the pulsed powers for thermal ablation. The results showed that for small source diameters (not larger than 4 mm), pulsed powers with high duties were more effective than continuous power. Although by increasing the source domain the fraction of damage caused by continuous power reached the damage caused by the pulsed powers, it affected the healthy tissues more (at least two times greater) than the pulsed powers. Pulsed powers with high duty (0.8 and 0.9) showed the optimized condition and the results have been explained based on the Arrhenius equation. Utilizing the pulsed powers for breast cancer treatment can potentially be an efficient approach for treating breast tumors due to requiring lower heating power and minimizing side effects to the healthy tissues.
    Keywords:  breast cancer; fraction of damage; hyperthermia; magnetic nanoparticles; pulsed heating power
  5. Pharmaceutics. 2021 Aug 12. pii: 1248. [Epub ahead of print]13(8):
      Multifunctional lipid nanocarriers are a promising therapeutic approach for controlled drug release in cancer therapy. Combining the widely used liposome structure with magnetic nanoparticles in magnetoliposomes allies, the advantages of using liposomes include the possibility to magnetically guide, selectively accumulate, and magnetically control the release of drugs on target. The effectiveness of these nanosystems is intrinsically related to the individual characteristics of the two main components-lipid formulation and magnetic nanoparticles-and their physicochemical combination. Herein, shape-anisotropic calcium-substituted magnesium ferrite nanoparticles (Ca0.25Mg0.75Fe2O4) were prepared for the first time, improving the magnetic properties of spherical counterparts. The nanoparticles revealed a superparamagnetic behavior, high saturation magnetization (50.07 emu/g at 300 K), and a large heating capacity. Furthermore, a new method for the synthesis of solid magnetoliposomes (SMLs) was developed to enhance their magnetic response. The manufacturing technicalities were optimized with different lipid compositions (DPPC, DPPC/Ch, and DPPC/DSPE-PEG) originating nanosystems with optimal sizes for biomedical applications (around or below 150 nm) and low polydispersity index. The high encapsulation efficiency of doxorubicin in these magnetoliposomes was proven, as well as the ability of the drug-loaded nanosystems to interact with cell membrane models and release DOX by fusion. SMLs revealed to reduce doxorubicin interaction with human serum albumin, contributing to a prolonged bioavailability of the drug upon systemic administration. Finally, the drug release kinetic assays revealed a preferable DOX release at hyperthermia temperatures (42 °C) and acidic conditions (pH = 5.5), indicating them as promising controlled release nanocarriers by either internal (pH) and external (alternate magnetic field) stimuli in cancer therapy.
    Keywords:  doxorubicin; magnetic hyperthermia; magnetic nanoparticles; magnetoliposomes; mixed ferrites; shape-anisotropy
  6. Molecules. 2021 Aug 20. pii: 5052. [Epub ahead of print]26(16):
      Biomimetic nanoparticles have recently emerged as a novel drug delivery platform to improve drug biocompatibility and specificity at the desired disease site, especially the tumour microenvironment. Conventional nanoparticles often encounter rapid clearance by the immune system and have poor drug-targeting effects. The rapid development of nanotechnology provides an opportunity to integrate different types of biomaterials onto the surface of nanoparticles, which enables them to mimic the natural biological features and functions of the cells. This mimicry strategy favours the escape of biomimetic nanoparticles from clearance by the immune system and reduces potential toxic side effects. Despite the rapid development in this field, not much has progressed to the clinical stage. Thus, there is an urgent need to develop biomimetic-based nanomedicine to produce a highly specific and effective drug delivery system, especially for malignant tumours, which can be used for clinical purposes. Here, the recent developments for various types of biomimetic nanoparticles are discussed, along with their applications for cancer imaging and treatments.
    Keywords:  active targeting; biomimetic; cancer therapy; imaging; immunotherapy; nanoparticles
  7. Kidney360. 2020 Jun;1(6): 561-568
      Gadolinium-based contrast agents (GBCAs) have provided much needed image enhancement in magnetic resonance imaging (MRI) important in the advancement of disease diagnosis and treatment. The paramagnetic properties of ionized gadolinium have facilitated these advancements, but ionized gadolinium carries toxicity risk. GBCAs were formulated with organic chelates designed to reduce these toxicity risks from unbound gadolinium ions. They were preferred over iodinated contrast used in computed tomography and considered safe for use. As their use expanded, the development of new diseases associated with their use (including nephrogenic systemic fibrosis) has drawn more attention and ultimately caution with their clinical administration in those with impaired renal function. Use of GBCAs in those with preserved renal function was considered to be safe. However, in this new era with emerging clinical and experimental evidence of brain gadolinium deposition in those with repeated exposure, these safety assumptions are once again brought into question. This review article aims to add new perspectives in thinking about the role of GBCA in current clinical use. The new information begs for further discussion and consideration of the risk-benefit ratio of use of GBCAs.
  8. Langmuir. 2021 Aug 26.
      This paper (part II) is devoted to the effect of molecular adsorption on the surface of magnetic iron oxide nanoparticles (IONP) on the enhancement of their (secondary) field-induced agglomeration and magnetic separation. Experimentally, we use Methylene Blue (MB) cationic dye adsorption on citrate-coated maghemite nanoparticles to provoke primary agglomeration of IONP in the absence of the field. The secondary agglomeration is manifested through the appearance of needlelike micron-sized agglomerates in the presence of an applied magnetic field. With the increasing amount of adsorbed MB molecules, the size of the field-induced agglomerates increases and the magnetic separation on a magnetized micropillar becomes more efficient. These effects are mainly governed by the ratio of magnetic-to-thermal energy α, suspension supersaturation Δ0, and Brownian diffusivity Deff of primary agglomerates. The three parameters (α, Δ0, and Deff) are implicitly related to the surface coverage θ of IONP by MB molecules through the hydrodynamic size of primary agglomerates exponentially increasing with θ. Experiments and developed theoretical models allow quantitative evaluation of the θ effect on the efficiency of the secondary agglomeration and magnetic separation.
  9. Curr Opin Biomed Eng. 2021 Sep;pii: 100295. [Epub ahead of print]19
      Antibodies are extremely valuable tools in modern medicine due to their ability to target diseased cells through selective antigen binding and thereby regulate cellular signaling or inhibit cell-cell interactions with high specificity. However, the therapeutic utility of freely delivered antibodies is limited by high production costs, low efficacy, dose-limiting toxicities, and inability to cross the cellular membrane (which hinders antibodies against intracellular targets). To overcome these limitations, researchers have begun to develop nanocarriers that can improve antibodies' delivery efficiency, safety profile, and clinical potential. This review summarizes recent advances in the design and implementation of nanocarriers for extracellular or intracellular antibody delivery, emphasizing important design considerations, and points to future directions for the field.
    Keywords:  binding affinity; multivalency; nanoparticles; signal cascade interference; targeted antibodies
  10. ACS Synth Biol. 2021 Aug 24.
      The development of microbial cell factories requires robust synthetic biology tools to reduce design uncertainty and accelerate the design-build-test-learn process. Herein, we developed a suite of integrative genetic tools to facilitate the engineering of Rhodococcus, a genus of bacteria with considerable biocatalytic potential. We first created pRIME, a modular, copy-controlled integrative-vector, to provide a robust platform for strain engineering and characterizing genetic parts. This vector was then employed to benchmark a series of strong promoters. We found PM6 to be the strongest constitutive rhodococcal promoter, 2.5- to 3-fold stronger than the next in our study, while overall promoter activities ranged 23-fold between the weakest and strongest promoters during exponential growth. Next, we used an optimized variant of PM6 to develop hybrid-promoters and integrative vectors to allow for tetracycline-inducible gene expression in Rhodococcus. The best of the resulting hybrid-promoters maintained a maximal activity of ∼50% of PM6 and displayed an induction factor of ∼40-fold. Finally, we developed and implemented a uLoop-derived Golden Gate assembly strategy for high-throughput DNA assembly in Rhodococcus. To demonstrate the utility of our approaches, pRIME was used to engineer Rhodococcus jostii RHA1 to grow on vanillin at concentrations 10-fold higher than what the wild-type strain tolerated. Overall, this study provides a suite of tools that will accelerate the engineering of Rhodococcus for various biocatalytic applications, including the sustainable production of chemicals from lignin-derived aromatics.
    Keywords:  Golden Gate assembly; Rhodococcus; metabolic engineering; microbial cell factory; promoter engineering; site-specific integrase
  11. Mol Biotechnol. 2021 Aug 21.
      Recently an enormous expansion of knowledge is seen in various disciplines of science. This surge of information has given rise to concept of interdisciplinary fields, which has resulted in emergence of newer research domains, one of them is 'Synthetic Biology' (SynBio). It captures basics from core biology and integrates it with concepts from the other areas of study such as chemical, electrical, and computational sciences. The essence of synthetic biology is to rewire, re-program, and re-create natural biological pathways, which are carried through genetic circuits. A genetic circuit is a functional assembly of basic biological entities (DNA, RNA, proteins), created using typical design, built, and test cycles. These circuits allow scientists to engineer nearly all biological systems for various useful purposes. The development of sophisticated molecular tools, techniques, genomic programs, and ease of nucleic acid synthesis have further fueled several innovative application of synthetic biology in areas like molecular medicines, pharmaceuticals, biofuels, drug discovery, metabolomics, developing plant biosensors, utilization of prokaryotic systems for metabolite production, and CRISPR/Cas9 in the crop improvement. These applications have largely been dominated by utilization of prokaryotic systems. However, newer researches have indicated positive growth of SynBio for the eukaryotic systems as well. This paper explores advances of synthetic biology in the plant field by elaborating on its core components and potential applications. Here, we have given a comprehensive idea of designing, development, and utilization of synthetic biology in the improvement of the present research state of plant system.
    Keywords:  Biosensors; CRISPR/Cas9; Computational biology; Metabolic engineering; Synthetic biology