bims-mricoa Biomed News
on MRI contrast agents
Issue of 2021‒11‒14
six papers selected by
Merve Yavuz
Bilkent University

  1. Materials (Basel). 2021 Oct 26. pii: 6416. [Epub ahead of print]14(21):
      The increasing use of magnetic nanoparticles as heating agents in biomedicine is driven by their proven utility in hyperthermia therapeutic treatments and heat-triggered drug delivery methods. The growing demand of efficient and versatile nanoheaters has prompted the creation of novel types of magnetic nanoparticle systems exploiting the magnetic interaction (exchange or dipolar in nature) between two or more constituent magnetic elements (magnetic phases, primary nanoparticles) to enhance and tune the heating power. This process occurred in parallel with the progress in the methods for the chemical synthesis of nanostructures and in the comprehension of magnetic phenomena at the nanoscale. Therefore, complex magnetic architectures have been realized that we classify as: (a) core/shell nanoparticles; (b) multicore nanoparticles; (c) linear aggregates; (d) hybrid systems; (e) mixed nanoparticle systems. After a general introduction to the magnetic heating phenomenology, we illustrate the different classes of nanoparticle systems and the strategic novelty they represent. We review some of the research works that have significantly contributed to clarify the relationship between the compositional and structural properties, as determined by the synthetic process, the magnetic properties and the heating mechanism.
    Keywords:  chemical synthesis; core/shell nanoparticles; hybrid systems; magnetic aggregates; magnetic heating; magnetic hyperthermia; magnetic interactions; magnetic nanoparticles; mixed nanoparticle systems; multicore nanoparticles
  2. Cancers (Basel). 2021 Oct 21. pii: 5285. [Epub ahead of print]13(21):
      BACKGROUND: Magnetic Particle Imaging (MPI) is an emerging imaging modality for quantitative direct imaging of superparamagnetic iron oxide nanoparticles (SPION or SPIO). With different physics from MRI, MPI benefits from ideal image contrast with zero background tissue signal. This enables clear visualization of cancer with image characteristics similar to PET or SPECT, but using radiation-free magnetic nanoparticles instead, with infinite-duration reporter persistence in vivo. MPI for cancer imaging: demonstrated months of quantitative imaging of the cancer-related immune response with in situ SPION-labelling of immune cells (e.g., neutrophils, CAR T-cells). Because MPI suffers absolutely no susceptibility artifacts in the lung, immuno-MPI could soon provide completely noninvasive early-stage diagnosis and treatment monitoring of lung cancers. MPI for magnetic steering: MPI gradients are ~150 × stronger than MRI, enabling remote magnetic steering of magneto-aerosol, nanoparticles, and catheter tips, enhancing therapeutic delivery by magnetic means. MPI for precision therapy: gradients enable focusing of magnetic hyperthermia and magnetic-actuated drug release with up to 2 mm precision. The extent of drug release from the magnetic nanocarrier can be quantitatively monitored by MPI of SPION's MPS spectral changes within the nanocarrier.CONCLUSION: MPI is a promising new magnetic modality spanning cancer imaging to guided-therapy.
    Keywords:  magnetic drug delivery; magnetic hyperthermia; magnetic nanoparticles; magnetic particle imaging
  3. Nanomedicine. 2021 Nov 04. pii: S1549-9634(21)00121-0. [Epub ahead of print] 102478
      Precise detection of brain regions harboring heightened electrical activity plays a central role in the understanding and treatment of diseases such as epilepsy. Superparamagnetic iron oxide nanoparticles (SPIONs) react to magnetic fields by aggregating and represent interesting candidates as new sensors for neuronal magnetic activity. We hypothesized that SPIONs in aqueous solution close to active brain tissue would aggregate proportionally to neuronal activity. We tested this hypothesis using an in vitro model of rat brain slice with different levels of activity. Aggregation was assessed with dynamic light scattering (DLS) and magnetic resonance imaging (MRI). We found that increasing brain slice activity was associated with higher levels of aggregation as measured by DLS and MRI, suggesting that the magnetic fields from neuronal tissue could induce aggregation in nearby SPIONs in solution. MRI signal change induced by SPIONs aggregation could serve as a powerful new tool for detection of brain electrical activity.
    Keywords:  Brain activity; Epilepsy; Magnetic resonance imaging; Nanoparticle aggregation; iron oxide nanoparticles
  4. Nanoscale Adv. 2021 Oct 12. 3(20): 5890-5899
      Iron oxide nanoparticles (IONPs) have often been investigated for tumor hyperthermia. IONPs act as heating foci in the presence of an alternating magnetic field (AMF). It has been shown that hyperthermia can significantly alter the tumor immune microenvironment. Typically, mild hyperthermia invokes morphological changes within the tumor, which elicits a secretion of inflammatory cytokines and tumor neoantigens. Here, we focused on the direct effect of IONP-induced hyperthermia on the various tumor-resident immune cell subpopulations. We compared direct intratumoral injection to systemic administration of IONPs followed by application of an external AMF. We used the orthotopic 4T1 mouse model, which represents aggressive and metastatic breast cancer with a highly immunosuppressive microenvironment. A non-inflamed and 'cold' microenvironment inhibits peripheral effector lymphocytes from effectively trafficking into the tumor. Using intratumoral or systemic injection, IONP-induced hyperthermia achieved a significant reduction of all the immune cell subpopulations in the tumor. However, the systemic delivery approach achieved superior outcomes, resulting in substantial reductions in the populations of both innate and adaptive immune cells. Upon depletion of the existing dysfunctional tumor-resident immune cells, subsequent treatment with clinically approved immune checkpoint inhibitors encouraged the repopulation of the tumor with 'fresh' infiltrating innate and adaptive immune cells, resulting in a significant decrease of the tumor cell population.
  5. Methods Enzymol. 2021 ;pii: S0076-6879(21)00191-9. [Epub ahead of print]660 81-104
      Engineered promoters are key components that allow engineered expression of genes in the cell-factory design. Promoters having exceptional strength are attractive candidates for designing metabolic engineering strategies for tailoring de novo production strategies that require directed evolution methods by engineering with de novo synthetic biology tools. Engineered promoter variants (EPVs) of naturally occurring promoters (NOPs) can be designed using metabolic engineering strategies and synthetic biology tools if the genes encoding the activating transcription factors (TFs) exist in the genome and are expressed and synthesized at non-limiting concentrations within the cell. The hybrid-architectured EPV design method targets an essential and predetermined part of the general transcription machinery. That is cis-acting DNA site(s) in coordination with the trans-acting factor(s) that must bind for the regulated transcription machinery activation. The method needs genomic and functional information that can lead to the discovery of the master TF(s) and synthetic cis-acting DNA elements, enabling the engineering of binding of master regulator TF(s). The method aims to generate EPVs that combine the advantages of being an exceptional stronger EPV(s) than the NOPs and permit "green-and-clean production" on a non-toxic carbon source, such as ethanol or glucose. By introducing our recent work on the engineering of ADH2 hybrid-promoter architectures to enhance recombinant protein expression on ethanol, we provide the method and protocol for the design of ADH2 hybrid-promoter architectures that can be adapted to other promoters in different substrate utilization pathways in Pichia pastoris (syn. Komagataella phaffii), as well as in other yeasts.
    Keywords:  Alcohol dehydrogenase 2 (ADH2) promoter; Engineering expression; Hybrid-architectured promoter; Master transcription factor; Pichia pastoris; Synthetic cis-acting DNA sites
  6. J Control Release. 2021 Oct 29. pii: S0168-3659(21)00582-4. [Epub ahead of print]340 221-242
      A bird's eye view is now demanded in the area of cancer research to suppress the suffering of cancer patient and mediate the lack of treatment related to chemotherapy. Chemotherapy is always preferred over surgery or radiation therapy, but they never met the patient's demand of safe medication. Targeted therapy has now been in research that could hinder the unnecessary effect of drug on normal cells but could affect the tumor cells in much efficient manner. Angiogenesis is process involved in development of new blood vessel that nourishes tumor growth. Integrin receptors are over expressed on cancer cells that play vital role in angiogenesis for growth and metastasis of tumor cell. A delivery of RGD based peptide to integrin targeted site could help in its successful binding and liberation of drug in tumor vasculature. Dendrimers, in addition to its excellent pharmacokinetic properties also helps to carry targeting ligand to site of tumor by successfully conjugating with them. The aim of this review is to bring light upon the role of integrin in cancer progression, interaction of RGD to integrin receptor and more importantly the RGD-dendrimer based targeted therapy for the treatment of various cancers.
    Keywords:  Cancer; Dendrimer; Integrin; Nanotechnology; Peptide; RGD; Targeted therapy