bims-mricoa Biomed News
on MRI contrast agents
Issue of 2021–08–15
seven papers selected by
Merve Yavuz, Bilkent University
  1. Recent progress in magnetic applications for micro- and nanorobots.
  2. Biocompatible dextran-coated gadolinium-doped cerium oxide nanoparticles as MRI contrast agents with high T1 relaxivity and selective cytotoxicity to cancer cells.
  3. Targeting iron metabolism in cancer therapy.
  4. Towards Tumor Targeting via Invasive Assay Using Magnetospirillum magneticum.
  5. Detection of PD-L1 Expression in Temozolomide-Resistant Glioblastoma by Using PD-L1 Antibodies Conjugated with Lipid‑Coated Superparamagnetic Iron Oxide.
  6. Mechanisms of cellular iron sensing, regulation of erythropoiesis and mitochondrial iron utilization.
  7. Iron Homeostasis and Metabolism: Two Sides of a Coin.
  1. Beilstein J Nanotechnol. 2021 ;12 744-755
    Recent progress in magnetic applications for micro- and nanorobots.
    Ke Xu, Shuang Xu, Fanan Wei.
      In recent years, magnetic micro- and nanorobots have been developed and extensively used in many fields. Actuated by magnetic fields, micro- and nanorobots can achieve controllable motion, targeted transportation of cargo, and energy transmission. The proper use of magnetic fields is essential for the further research and development of micro- and nanorobotics. In this article, recent progress in magnetic applications in the field of micro- and nanorobots is reviewed. First, the achievements of manufacturing micro- and nanorobots by incorporating different magnetic nanoparticles, such as diamagnetic, paramagnetic, and ferromagnetic materials, are discussed in detail, highlighting the importance of a rational use of magnetic materials. Then the innovative breakthroughs of using different magnetoelectric devices and magnetic drive structures to improve the micro- and nanorobots are reviewed. Finally, based on the biofriendliness and the precise and stable performance of magnetic micro- and nanorobots in microbial environments, some future challenges are outlined, and the prospects of magnetic applications for micro- and nanorobots are presented.
    Keywords:  magnetic drives; magnetic nanoparticles; magnetoelectric devices; micro- and nanorobots
    DOI:  https://doi.org/10.3762/bjnano.12.58
  2. J Mater Chem B. 2021 Aug 09.
    Biocompatible dextran-coated gadolinium-doped cerium oxide nanoparticles as MRI contrast agents with high T1 relaxivity and selective cytotoxicity to cancer cells.
    A L Popov, M A Abakumov, I V Savintseva, A M Ermakov, N R Popova, O S Ivanova, D D Kolmanovich, A E Baranchikov, V K Ivanov.
      Gd-based complexes are widely used as magnetic resonance imaging (MRI) contrast agents. The safety of previously approved contrast agents is questionable and is being re-assessed. The main causes of concern are possible gadolinium deposition in the brain and the development of systemic nephrogenic fibrosis after repeated use of MRI contrasts. Thus, there is an urgent need to develop a new generation of MRI contrasts that are safe and that have high selectivity in tissue accumulation with improved local contrast. Here, we report on a new type of theranostic MRI contrast, namely dextran stabilised, gadolinium doped cerium dioxide nanoparticles. These ultra-small (4-6 nm) Ce0.9Gd0.1O1.95 nanoparticles have been shown to possess excellent colloidal stability and high r1-relaxivity (3.6 mM-1 s-1). They are effectively internalised by human normal and cancer cells and demonstrate dose-dependent selective cytotoxicity to cancer cells.
    DOI:  https://doi.org/10.1039/d1tb01147b
  3. Theranostics. 2021 ;11(17): 8412-8429
    Targeting iron metabolism in cancer therapy.
    Michael Morales, Xiang Xue.
      Iron is a critical component of many cellular functions including DNA replication and repair, and it is essential for cell vitality. As an essential element, iron is critical for maintaining human health. However, excess iron can be highly toxic, resulting in oxidative DNA damage. Many studies have observed significant associations between iron and cancer, and the association appears to be more than just coincidental. The chief characteristic of cancers, hyper-proliferation, makes them even more dependent on iron than normal cells. Cancer therapeutics are becoming as diverse as the disease itself. Targeting iron metabolism in cancer cells is an emerging, formidable field of therapeutics. It is a strategy that is highly diverse with regard to specific targets and the various ways to reach them. This review will discuss the importance of iron metabolism in cancer and highlight the ways in which it is being explored as the medicine of tomorrow.
    Keywords:  Cancer; Chelation; Ferroptosis; Iron metabolism; Therapy
    DOI:  https://doi.org/10.7150/thno.59092
  4. Front Microbiol. 2021 ;12 697132
    Towards Tumor Targeting via Invasive Assay Using Magnetospirillum magneticum.
    Marvin Xavierselvan, Heena R Divecha, Mamta Hajra, Sushila Silwal, Isaac Macwan.
      Magnetospirillum magneticum (AMB-1) are a species of magnetotactic bacteria (MTB) that are capable of orienting along the earth's magnetic field lines through their organelles called magnetosomes. Many studies have shown that certain engineered bacteria can infect the tumor cells, resulting in a controlled death of a tumor. This work deals with a technique utilizing AMB-1 along a predefined path through magnetotaxis, which can pave a way for selective doping as well as isolation of the tumor cells from a group of healthy cells through a magnetic invasive assay. For such a control, a tiny mesh of vertical electrical coils each having a diameter of ∼3 mm is fabricated, which establishes the path for the bacteria to move along the magnetic field lines. The molecular dynamics (MD) simulations at the interface of the bacterial cell surface proteins (MSP-1 and flagellin) and Chinese hamster ovary (CHO) cell surface containing cytoplasmic and extracellular proteins (BSG, B2M, SDC1, AIMP1, and FOS) are shown to establish an association between the AMB-1 and the host CHO cells. It is found that the CHO protein structure is compromised, which disables the activation of its defense function, allowing the bacteria to interact and survive. The experimental demonstration involves the CHO cells' interaction with the AMB-1 and isolation of selected CHO cells. It is found that AMB-1-integrated CHO cells successfully moved along the magnetic field lines generated by the coils. Statistical analysis performed for the assay showed that AMB-1 cells were found to be viable after co-incubating with CHO cells, and the number of viable cells post co-incubation over a period of 24 h showed a slight decrease in both cell population. Overall, 51% of AMB-1 cells and 67% of CHO cells were found viable 24 h post co-incubation. Scanning electron microscopy (SEM) along with energy-dispersive X-ray spectroscopy (EDAX) analysis revealed AMB-1/CHO cell morphology, the potential interaction between them, and the presence of magnetosomes with trace amounts of iron in the AMB-1-interacted CHO cells, confirming the successful AMB-1 integration.
    Keywords:  AMB-1; VMD simulation; bacterial invasion; magnetotaxis; tumor targeting
    DOI:  https://doi.org/10.3389/fmicb.2021.697132
  5. Int J Nanomedicine. 2021 ;16 5233-5246
    Detection of PD-L1 Expression in Temozolomide-Resistant Glioblastoma by Using PD-L1 Antibodies Conjugated with Lipid‑Coated Superparamagnetic Iron Oxide.
    Gilbert Aaron Lee, Wan-Li Lin, Duen-Pang Kuo, Yi-Tien Li, Yu-Wei Chang, Yung-Chieh Chen, Shiu-Wen Huang, Justin Bo-Kai Hsu, Cheng-Yu Chen.
       Purpose: Targeted superparamagnetic iron oxide (SPIO) nanoparticles are a promising tool for molecular magnetic resonance imaging (MRI) diagnosis. Lipid-coated SPIO nanoparticles have a nonfouling property that can reduce nonspecific binding to off-target cells and prevent agglomeration, making them suitable contrast agents for molecular MRI diagnosis. PD-L1 is a poor prognostic factor for patients with glioblastoma. Most recurrent glioblastomas are temozolomide resistant. Diagnostic probes targeting PD-L1 could facilitate early diagnosis and be used to predict responses to targeted PD-L1 immunotherapy in patients with primary or recurrent glioblastoma. We conjugated lipid-coated SPIO nanoparticles with PD-L1 antibodies to identify PD-L1 expression in glioblastoma or temozolomide-resistant glioblastoma by using MRI.
    Methods: The synthesized PD-L1 antibody-conjugated SPIO (PDL1-SPIO) nanoparticles were characterized using dynamic light scattering, zeta potential assays, transmission electron microscopy images, Prussian blue assay, in vitro cell affinity assay, and animal MRI analysis.
    Results: PDL1-SPIO exhibited a specific binding capacity to PD-L1 of the mouse glioblastoma cell line (GL261). The presence and quantity of PDL1-SPIO in temozolomide-resistant glioblastoma cells and tumor tissue were confirmed through Prussian blue staining and in vivo T2* map MRI, respectively.
    Conclusion: This is the first study to demonstrate that PDL1-SPIO can specifically target temozolomide-resistant glioblastoma with PD-L1 expression in the brain and can be quantified through MRI analysis, thus making it suitable for the diagnosis of PD-L1 expression in temozolomide-resistant glioblastoma in vivo.
    Keywords:  MRI; PD-L1; SPIO; glioblastoma; lipid-coated nanoparticle; magnetic resonance imaging; superparamagnetic iron oxide
    DOI:  https://doi.org/10.2147/IJN.S310464
  6. Semin Hematol. 2021 Jul;pii: S0037-1963(21)00033-0. [Epub ahead of print]58(3): 161-174
    Mechanisms of cellular iron sensing, regulation of erythropoiesis and mitochondrial iron utilization.
    Nunziata Maio, De-Liang Zhang, Manik C Ghosh, Anshika Jain, Anna M SantaMaria, Tracey A Rouault.
      To maintain an adequate iron supply for hemoglobin synthesis and essential metabolic functions while counteracting iron toxicity, humans and other vertebrates have evolved effective mechanisms to conserve and finely regulate iron concentration, storage, and distribution to tissues. At the systemic level, the iron-regulatory hormone hepcidin is secreted by the liver in response to serum iron levels and inflammation. Hepcidin regulates the expression of the sole known mammalian iron exporter, ferroportin, to control dietary absorption, storage and tissue distribution of iron. At the cellular level, iron regulatory proteins 1 and 2 (IRP1 and IRP2) register cytosolic iron concentrations and post-transcriptionally regulate the expression of iron metabolism genes to optimize iron availability for essential cellular processes, including heme biosynthesis and iron-sulfur cluster biogenesis. Genetic malfunctions affecting the iron sensing mechanisms or the main pathways that utilize iron in the cell cause a broad range of human diseases, some of which are characterized by mitochondrial iron accumulation. This review will discuss the mechanisms of systemic and cellular iron sensing with a focus on the main iron utilization pathways in the cell, and on human conditions that arise from compromised function of the regulatory axes that control iron homeostasis.
    Keywords:  Ferroportin; Heme biosynthesis; IRP1; IRP2; Iron metabolism; Iron-sulfur clusters
    DOI:  https://doi.org/10.1053/j.seminhematol.2021.06.001
  7. Adv Exp Med Biol. 2021 ;1301 25-40
    Iron Homeostasis and Metabolism: Two Sides of a Coin.
    Vivek Venkataramani.
      Iron is an ancient, essential and versatile transition metal found in almost all living organisms on Earth. This fundamental trace element is used in the synthesis of heme and iron-sulfur (Fe-S) containing proteins and other vital cofactors that are involved in respiration, redox reactions, catalysis, DNA synthesis and transcription. At the same time, the ability of iron to cycle between its oxidized, ferric (Fe3+) and its reduced, ferrous (Fe2+) state contributes to the production of free radicals that can damage biomolecules, including proteins, lipids and DNA. In particular, the regulated non-apoptotic cell death ferroptosis is driven by Fe2+-dependent lipid peroxidation that can be prevented by iron chelation or genetic inhibition of cellular iron uptake. Therefore, iron homeostasis must be tightly regulated to avoid iron toxicity. This review provides an overview of the origin and chemistry of iron that makes it suitable for a variety of biological functions and addresses how organisms evolved various strategies, including their scavenging and antioxidant machinery, to manage redox-associated drawbacks. Finally, key mechanisms of iron metabolism are highlighted in human diseases and model organisms, underlining the perils of dysfunctional iron handlings.
    Keywords:  Fe2+; Fe3+; Ferroptosis; Heme; Iron assimilation; Iron storage; Iron transport; Iron-sulfur-cluster; Lipid peroxidation; Oxidative stress; Reactive oxygen species
    DOI:  https://doi.org/10.1007/978-3-030-62026-4_3
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