bims-mricoa Biomed News
on MRI contrast agents
Issue of 2022‒05‒22
six papers selected by
Merve Yavuz
Bilkent University

  1. Front Bioeng Biotechnol. 2022 ;10 870675
      Future advances in therapeutics demand the development of dynamic and intelligent living materials. The past static monofunctional materials shall be unable to meet the requirements of future medical development. Also, the demand for precision medicine has increased with the progressively developing human society. Therefore, engineered living materials (ELMs) are vitally important for biotherapeutic applications. These ELMs can be cells, microbes, biofilms, and spores, representing a new platform for treating intractable diseases. Synthetic biology plays a crucial role in the engineering of these living entities. Hence, in this review, the role of synthetic biology in designing and creating genetically engineered novel living materials, particularly bacteria, has been briefly summarized for diagnostic and targeted delivery. The main focus is to provide knowledge about the recent advances in engineered bacterial-based therapies, especially in the treatment of cancer, inflammatory bowel diseases, and infection. Microorganisms, particularly probiotics, have been engineered for synthetic living therapies. Furthermore, these programmable bacteria are designed to sense input signals and respond to disease-changing environments with multipronged therapeutic outputs. These ELMs will open a new path for the synthesis of regenerative medicines as they release therapeutics that provide in situ drug delivery with lower systemic effects. In last, the challenges being faced in this field and the future directions requiring breakthroughs have been discussed. Conclusively, the intent is to present the recent advances in research and biomedical applications of engineered bacteria-based therapies during the last 5 years, as a novel treatment for uncontrollable diseases.
    Keywords:  biodiagnostic; biotherapeutics; engineered living materials; multiplex diseases; synthetic biology; synthetic live therapy
  2. Adv Exp Med Biol. 2022 ;1357 303-350
      Iron oxide nanoparticles (ION), with unique magnetic properties, have attracted huge scientific attention for a wide variety of uses, mostly in the biomedical field, due to their high biocompatibility, ability to cross biological membranes, appropriate surface architecture and easy conjugation with targeting ligands. Their current applications include diagnostic imaging, cell labelling, site-directed drug delivery and anticancer hyperthermia therapy. The ION surface may be modified by coating with different materials, aiming to stabilize the nanoparticles in different environments, to allow biomolecule binding favouring surface attachments with several molecules, and to prolong the recognition time by the immune system. Although the potential benefits of ION are considerable, and more and more ION are being manufactured to meet the demands of the rapidly proliferating field of nanomedicine, there is an urgent need to define their toxicological profile in order to avoid any potential health risks associated with their exposure and to reach optimal benefits of their use. The purpose of this chapter is to de-scribe the current knowledge on the ION toxicological features, addressing their structure and physicochemical characteristics, main exposure pathways and toxicokinetic aspects, interaction with cells, and their toxic effects, with special attention to those at the cellular and molecular level.
    Keywords:  Cellular uptake; Cytotoxicity; Genotoxicity; Iron oxide nanoparticles; Physicochemical properties
  3. ACS Omega. 2022 May 10. 7(18): 15996-16012
      In this study, a comprehensive characterization of iron oxide nanoparticles synthesized by using a simple one-pot thermal decomposition route is presented. In order to obtain monodisperse magnetite nanoparticles with high saturation magnetization, close to the bulk material, the molar ratios between the starting materials (solvents, reducing agents, and surfactants) were varied. Two out of nine conditions investigated in this study resulted in monodisperse iron oxide nanoparticles with high saturation magnetization (90 and 93% of bulk magnetite). The X-ray diffraction analyses along with the inspection of the lattice structure through transmission electron micrographs revealed that the main cause of the reduced magnetization in the other seven samples is likely due to the presence of distortion and microstrain in the particles. Although the thermogravimetric analysis, Raman and Fourier transform infrared spectroscopies confirmed the presence of covalently bonded oleic acid on the surface of all the samples, the particles with higher polydispersity and the lowest surface coating molecules showed the lowest saturation magnetization. Based on the observed results, it could be speculated that the changes in the kinetics of the reactions, induced by varying the molar ratio of the starting chemicals, can lead to the production of the particles with higher polydispersity and/or lattice deformation in their crystal structures. Finally, it was concluded that the experimental conditions for obtaining high-quality iron oxide nanoparticles, particularly the molar ratios and the heating profile, should not be chosen independently; for any specific molar ratio, there may exist a specific heating profile or vice versa. Because this synthetic consideration has rarely been reported in the literature, our results can give insights into the design of iron oxide nanoparticles with high saturation magnetization for different applications.
  4. Curr Opin Microbiol. 2022 May 16. pii: S1369-5274(22)00039-X. [Epub ahead of print]68 102155
      Synthetic biology (SynBio) is a field at the intersection of biology and engineering. Inspired by engineering principles, researchers use defined parts to build functionally defined biological circuits. Genetic design automation (GDA) allows scientists to design, model, and analyze their genetic circuits in silico before building them in the lab, saving time, and resources in the process. Establishing SynBio's future is dependent on GDA, since the computational approach opens the field to a broad, interdisciplinary community. However, challenges with part libraries, standards, and software tools are currently stalling progress in the field. This review first covers recent advancements in GDA, followed by an assessment of the challenges ahead, and a proposed automated genetic design workflow for the future.
    Keywords:  Genetic Design Automaton; Part libraries; Software Tools; Standards; Synthetic Biology
  5. Nature. 2022 May 18.
      Cellular iron homeostasis is vital and maintained through tight regulation of iron import, efflux, storage and detoxification1-3. The most common modes of iron storage use proteinaceous compartments, such as ferritins and related proteins4,5. Although lipid-bounded iron compartments have also been described, the basis for their formation and function remains unknown6,7. Here we focus on one such compartment, herein named the 'ferrosome', that was previously observed in the anaerobic bacterium Desulfovibrio magneticus6. Using a proteomic approach, we identify three ferrosome-associated (Fez) proteins that are responsible for forming ferrosomes in D. magneticus. Fez proteins are encoded in a putative operon and include FezB, a P1B-6-ATPase found in phylogenetically and metabolically diverse species of bacteria and archaea. We show that two other bacterial species, Rhodopseudomonas palustris and Shewanella putrefaciens, make ferrosomes through the action of their six-gene fez operon. Additionally, we find that fez operons are sufficient for ferrosome formation in foreign hosts. Using S. putrefaciens as a model, we show that ferrosomes probably have a role in the anaerobic adaptation to iron starvation. Overall, this work establishes ferrosomes as a new class of iron storage organelles and sets the stage for studying their formation and structure in diverse microorganisms.
  6. ACS Synth Biol. 2022 May 17.
      Phycocyanobilin (PCB) is a kind of light-harvesting pigment which naturally exists in algae and plays important roles in absorbing and transferring energy. Based on its antioxidant and optical properties, PCB has been applied in food, medicine, and cosmetics. Currently, PCB is mainly extracted from Spirulina through complicated steps; thus, the biosynthesis of PCB in Escherichia coli has attracted more attention. However, due to the lower catalytic efficiency of synthetic enzymes and the deficiency of precursors and cofactors, the titer of PCB remains at a low level. Here, we report the efficient synthesis of PCB by the expression of heme oxygenase-1 from Thermosynechococcus elongatus and PCB: ferredoxin oxidoreductase (PcyA) from Synechocystis sp. using a high-copy number plasmid with an inducible T7lac promoter and the assembly of these two enzymes at a suitable ratio of 2:1 with DNA scaffolds. Additionally, the synthesis of PCB was further enhanced by direct supplementation of 5-aminolevulinic acid (ALA), moderate overexpression of key enzymes in the heme biosynthetic pathway (hemB and hemH), and accelerated cycle of cofactors (NADPH) through the expression of NAD+ kinase and the addition of a reducing agent. Finally, based on the optimal conditions (Modified R medium with 200 mg/L ALA, 20 mg/L FeSO4·7H2O, and 5 g/L vitamin C induced by 0.8 mM isopropylthio-β-galactoside at 30 °C), the highest reported titer of PCB (28.32 mg/L) was obtained at the fermenter level by feeding glucose and FeSO4·7H2O. The strategies applied in this study will be useful for the synthesis of other natural pigments and PCB or heme derivatives in E. coli.
    Keywords:  5-aminolevulinic acid; DNA scaffold; Escherichia coli; cofactor; fed batch; heme; phycocyanobilin; reducing agent