bims-mricoa 2021-12-12 papers

bims-mricoa

Biomed News

on MRI contrast agents

Issue of 2021–12–12
ten papers selected by
Merve Yavuz, Bilkent University

Fighting Cancer with Bacteria and Their Toxins.
Recent Technologies for Genetic Code Expansion and their Implications on Synthetic Biology Applications.
Molecularly Imprinted Polymer Hydrogel Nanoparticles: Synthetic Antibodies for Cancer Diagnosis and Therapy.
Rational Design of Peptide-based Smart Hydrogels for Therapeutic Applications.
Molecular Diagnostic System Using Engineered Fusion Protein-Conjugated Magnetic Nanoparticles.
Genomic and Synthetic Biology Digital Biosecurity.
Bioremediation of Industrial Pollutants by Insects Expressing a Fungal Laccase.
Multifunctional Photoactive Hydrogels for Wound Healing Acceleration.
Development of a Nanoscale Chemical Exchange Saturation Transfer Magnetic Resonance Imaging Contrast Agent That Measures pH.
Cellular and molecular pathways underlying the nephrotoxicity of gadolinium.

Int J Mol Sci. 2021 Nov 30. pii: 12980. [Epub ahead of print]22(23):

Fighting Cancer with Bacteria and Their Toxins.

Dragan Trivanović, Krešimir Pavelić, Željka Peršurić.

  Cancer is one of the most important global health problems that continues to demand new treatment strategies. Many bacteria that cause persistent infections play a role in carcinogenesis. However, since bacteria are well studied in terms of molecular mechanisms, they have been proposed as an interesting solution to treat cancer. In this review, we present the use of bacteria, and particularly bacterial toxins, in cancer therapy, highlighting the advantages and limitations of bacterial toxins. Proteomics, as one of the omics disciplines, is essential for the study of bacterial toxins. Advances in proteomics have contributed to better characterization of bacterial toxins, but also to the development of anticancer drugs based on bacterial toxins. In addition, we highlight the current state of knowledge in the rapidly developing field of bacterial extracellular vesicles, with a focus on their recent application as immunotherapeutic agents.

Keywords:  bacteria; bacterial toxins; extracellular vesicles; lung cancer; proteomics

DOI:  https://doi.org/10.3390/ijms222312980
J Mol Biol. 2021 Dec 01. pii: S0022-2836(21)00619-7. [Epub ahead of print] 167382

Recent Technologies for Genetic Code Expansion and their Implications on Synthetic Biology Applications.

Hongting Tang, Pan Zhang, Xiaozhou Luo.

  Genetic code expansion (GCE) enables the site-specific incorporation of non-canonical amino acids as novel building blocks for the investigation and manipulation of proteins. The advancement of genetic code expansion has been benefited from the development of synthetic biology, while genetic code expansion also helps to create more synthetic biology tools. In this review, we summarize recent advances in genetic code expansion brought by synthetic biology progresses, including engineering of the translation machinery, genome-wide codon reassignment, and the biosynthesis of non-canonical amino acids. We highlight the emerging application of this technology in construction of new synthetic biology parts, circuits, chassis, and products.

Keywords:  GCE optimization; Non-canonical amino acid biosynthesis; synthetic chassis; synthetic circuits; synthetic parts

DOI:  https://doi.org/10.1016/j.jmb.2021.167382
Chembiochem. 2021 Dec 06.

Molecularly Imprinted Polymer Hydrogel Nanoparticles: Synthetic Antibodies for Cancer Diagnosis and Therapy.

Bernadette Tse Sum Bui, Karsten Haupt.

  Cancer is a leading cause of death worldwide and according to the World Health Organization (WHO), accounted for 10 million deaths in 2020. Promising theranostic (therapy and diagnostic) agents in the treatment of cancer are nanomaterials, which have come to the forefront because of their small size approaching those of protein complexes in the human body, and of their easy functionalization giving access to nanocomposite materials with diverse functions (fluorescence, magnetic, stimuli-responsiveness…), and improved biocompatibility. Among them, affinity nanoparticles, often decorated with highly specific targeting ligands such as antibodies, aptamers, lectins and peptides, have enabled enhanced binding and exquisite recognition of biomarkers overexpressed in cancer cells. In this review, we describe an emerging class of targeting ligands, molecularly imprinted polymer hydrogel nanoparticles for their application in the early detection of disease, with the aim to improve diagnosis and treatment.

Keywords:  molecularly imprinted polymer : epitope imprinting : hydrogel : cancer : bioimaging

DOI:  https://doi.org/10.1002/cbic.202100598
Front Chem. 2021 ;9 770102

Rational Design of Peptide-based Smart Hydrogels for Therapeutic Applications.

Saurav Das, Debapratim Das.

  Peptide-based hydrogels have captivated remarkable attention in recent times and serve as an excellent platform for biomedical applications owing to the impressive amalgamation of unique properties such as biocompatibility, biodegradability, easily tunable hydrophilicity/hydrophobicity, modular incorporation of stimuli sensitivity and other functionalities, adjustable mechanical stiffness/rigidity and close mimicry to biological molecules. Putting all these on the same plate offers smart soft materials that can be used for tissue engineering, drug delivery, 3D bioprinting, wound healing to name a few. A plethora of work has been accomplished and a significant progress has been realized using these peptide-based platforms. However, designing hydrogelators with the desired functionalities and their self-assembled nanostructures is still highly serendipitous in nature and thus a roadmap providing guidelines toward designing and preparing these soft-materials and applying them for a desired goal is a pressing need of the hour. This review aims to provide a concise outline for that purpose and the design principles of peptide-based hydrogels along with their potential for biomedical applications are discussed with the help of selected recent reports.

Keywords:  drug delivery; hydrogel; peptide; self-assembly; stimuli responsive; tissue engineering

DOI:  https://doi.org/10.3389/fchem.2021.770102
Anal Chem. 2021 Dec 09.

Molecular Diagnostic System Using Engineered Fusion Protein-Conjugated Magnetic Nanoparticles.

Juyoung Kang, Donguk Kang, Gyuho Yeom, Chin-Ju Park.

To effectively control the spread of new infectious diseases, there is a need for highly sensitive diagnostic methods to detect viral nucleic acids rapidly. This study outlines a universal and simple detection strategy that uses magnetic nanoparticles (MNPs) and a novel MagR-MazE fusion protein for molecular diagnostics to facilitate sensitive detection. This study has engineered a novel MNP conjugate that can be generated easily, without using many chemical reagents. The technique is a nucleic acid detection method, using MagR-MazE fusion protein-conjugated MNPs, where the results can be visualized with the naked eye, regardless of the oligonucleotide sequences of the target in the lateral flow assay. This method could sensitively detect polymerase chain reaction (PCR) products of 16S ribosomal RNA (rRNA) and the 2019-nCoV-N-positive control gene in 5 min. It shows a low limit of detection (LoD) of 0.013 ng/μL for dsDNA. It is simpler and more rapid, sensitive, and versatile than other techniques, making it suitable for point-of-care testing. The proposed detection system and MNP conjugation strategy using a fusion protein can be widely applied to various fields requiring rapid on-site diagnosis.

DOI: https://doi.org/10.1021/acs.analchem.1c03247
Pac Symp Biocomput. 2022 ;27 402-406

Genomic and Synthetic Biology Digital Biosecurity.

Corey M Hudson, Nicholas D Pattengale, Ravishankar K Iyer, Zbigniew T Kalbarczyk, Nina Alli.

Trends toward automation of synthetic biology and the individualization of biology and medicine raise varied and critical security issues. Digital biosecurity brings together researchers working in secure algorithms, vulnerability assessments, and emerging threat models. The fundamental goal of this digital biosecurity workshop is to identify and present distinct areas of research around making the next generation of biology safer and more secure. The workshop will include a panel overview of the field, including representatives from academia, industry, and non-profits. It will also include novel presentations from the research community. We expect that attendees will leave this workshop with a new appreciation of the research and implementation challenges in maintaining the digital aspects of biosecurity.
ACS Synth Biol. 2021 Dec 09.

Bioremediation of Industrial Pollutants by Insects Expressing a Fungal Laccase.

Michael Clark, Kate Tepper, Kerstin Petroll, Sheemal Kumar, Anwar Sunna, Maciej Maselko.

  Inadequate management of household and industrial wastes poses major challenges to human and environmental health. Advances in synthetic biology may help address these challenges by engineering biological systems to perform new functions such as biomanufacturing of high-value compounds from low-value waste streams and bioremediation of industrial pollutants. The current emphasis on microbial systems for biomanufacturing, which often requires highly preprocessed inputs and sophisticated infrastructure, is not feasible for many waste streams. Furthermore, concerns about transgene biocontainment have limited the release of engineered microbes or plants for bioremediation. Engineering of animals may provide opportunities for utilizing various waste streams that are not suitable for microbial biomanufacturing while effective transgene biocontainment options should enable in situ bioremediation. Here, we engineer the model insect Drosophila melanogaster to express a functional laccase from the fungus Trametes trogii. Laccase-expressing flies reduced concentrations of the endocrine disruptor bisphenol A by more than 50% when present in their growth media. A lyophilized powder prepared from engineered adult flies retained substantial enzymatic activity, degrading more than 90% of bisphenol A and the textile dye indigo carmine in aqueous solutions. Our results demonstrate that transgenic animals may be used to bioremediate environmental contaminants in vivo and serve as novel production platforms for industrial enzymes. These results support further development of insects, and possibly other animals, as bioproduction platforms and their potential use in bioremediation.

Keywords:  Drosophila melanogaster; biomanufacturing; bioremediation; insect synthetic biology; laccase; waste management

DOI:  https://doi.org/10.1021/acssynbio.1c00427
ACS Nano. 2021 Dec 06.

Multifunctional Photoactive Hydrogels for Wound Healing Acceleration.

Aziz Maleki, Jiahui He, Shayesteh Bochani, Vahideh Nosrati, Mohammad-Ali Shahbazi, Baolin Guo.

  Light is an attractive tool that has a profound impact on modern medicine. Particularly, light-based photothermal therapy (PTT) and photodynamic therapy (PDT) show great application prospects in the prevention of wound infection and promoting wound healing. In addition, hydrogels have shown attractive advantages in the field of wound dressings due to their excellent biochemical effects. Therefore, multifunctional photoresponsive hydrogels (MPRHs) that integrate the advantages of light and hydrogels are increasingly used in biomedicine, especially in the field of wound repair. However, a comprehensive review of MPRHs for wound regeneration is still lacking. This review first focuses on various types of MPRHs prepared by diverse photosensitizers, photothermal agents (PHTAs) including transition metal sulfide/oxides nanomaterials, metal nanostructure-based PHTAs, carbon-based PHTAs, conjugated polymer or complex-based PHTAs, and/or photodynamic agents (PHDAs) such as ZnO-based, black-phosphorus-based, TiO2-based, and small organic molecule-based PHDAs. We also then discuss how PTT, PDT, and photothermal/photodynamic synergistic therapy can modulate the microenvironments of bacteria to inhibit infection. Overall, multifunctional hydrogels with both therapeutic and tissue regeneration capabilities have been discussed and existing challenges, as well as future research directions in the field of MPRHs and their application in wound management are argued.

Keywords:  antibacterial hydrogels; multifunctional hydrogels; photodynamic agents; photoresponsive hydrogels; photosensitizers; photothermal agents; tissue regeneration; wound dressing; wound healing

DOI:  https://doi.org/10.1021/acsnano.1c08334
ACS Nano. 2021 Dec 06.

Development of a Nanoscale Chemical Exchange Saturation Transfer Magnetic Resonance Imaging Contrast Agent That Measures pH.

Chathuri J Kombala, Aikaterini Kotrotsou, F William Schuler, Jorge de la Cerda, Jacqueline C Ma, Shu Zhang, Mark D Pagel.

  AcidoCEST MRI can measure the extracellular pH (pHe) of the tumor microenvironment in mouse models of human cancers and in patients who have cancer. However, chemical exchange saturation transfer (CEST) is an insensitive magnetic resonance imaging (MRI) contrast mechanism, requiring a high concentration of small-molecule agent to be delivered to the tumor. Herein, we developed a nanoscale CEST agent that can measure pH using acidoCEST MRI, which may decrease the requirement for high delivery concentrations of agent. We also developed a monomer agent for comparison to the polymer. After optimizing CEST experimental conditions, we determined that the polymer agent could be used during acidoCEST MRI studies at 125-fold and 488-fold lower concentration than the monomer agent and iopamidol, respectively. We also determined that both agents can measure pH with negligible dependence on temperature. However, pH measurements with both agents were dependent on concentration, which may be due to concentration-dependent changes in hydrogen bonding and/or steric hindrance. We performed in vivo acidoCEST MRI studies using the three agents to study a xenograft MDA-MB-231 model of mammary carcinoma. The tumor pHe measurements were 6.33 ± 0.12, 6.70 ± 0.15, and 6.85 ± 0.15 units with iopamidol, the monomer agent, and polymer agent, respectively. The higher pHe measurements with the monomer and polymer agents were attributed to the concentration dependence of these agents. This study demonstrated that nanoscale agents have merit for CEST MRI studies, but consideration should be given to the dependence of CEST contrast on the concentration of these agents.

Keywords:  chemical exchange saturation transfer; magnetic resonance imaging; pH imaging; polymer contrast agent; tumor acidosis

DOI:  https://doi.org/10.1021/acsnano.1c10107
Toxicol Sci. 2021 Dec 08. pii: kfab148. [Epub ahead of print]

Cellular and molecular pathways underlying the nephrotoxicity of gadolinium.

Nícia Reis Sousa, Susana Rocha, Alice Santos-Silva, Susana Coimbra, Maria João Valente.

  Mounting evidence on the short- and long-term adverse effects associated with gadolinium [Gd (III)]-based contrast agents used in magnetic resonance imaging have emerged in the past three decades. Safety issues arise from the release of Gd (III) from chelates and its deposition in tissues, which is exacerbated in patients with renal disease, since the kidney is the major excretion organ of most of these agents. This study aimed at unveiling the cellular and molecular mechanisms of nephrotoxicity of Gd (III), using an in vitro model of human proximal tubular cells (HK-2 cell line). Cell viability declined in a concentration- and time-dependent manner after exposure to GdCl3·6H2O. The estimated inhibitory concentrations (ICs) eliciting 1 to 50% of cell death, after 24 h of exposure, ranged from 3.4 to 340.5 µM. At toxic concentrations, exposure to Gd (III) led to disruption of the oxidative status, mitochondrial dysfunction, cell death by apoptosis, switching to necrosis at higher levels, and autophagic activation. Disturbance of the lipid metabolism was already observed at low-toxicity ICs, with accumulation of lipid droplets, and upregulation of genes related to both lipogenesis and lipolysis. Gd (III)-exposure, even at the subtoxic IC01, increased the expression of modulators of various signaling pathways involved in the development and progression of renal disease, including inflammation, hypoxia and fibrosis. Our results give new insights into the mechanisms underlying the nephrotoxic potential of Gd (III) and highlight the need to further clarify the risks versus benefits of the Gd (III)-based contrast agents currently in use.

Keywords:  Gadolinium; inflammation; lipid metabolism; mitochondrial dysfunction; nephrotoxicity; oxidative stress

DOI:  https://doi.org/10.1093/toxsci/kfab148