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

  1. Antibiotics (Basel). 2021 Jul 20. pii: 884. [Epub ahead of print]10(7):
      The use of metal oxide nanoparticles is one of the promising ways for overcoming antibiotic resistance in bacteria. Iron oxide nanoparticles (IONPs) have found wide applications in different fields of biomedicine. Several studies have suggested using the antimicrobial potential of IONPs. Iron is one of the key microelements and plays an important role in the function of living systems of different hierarchies. Iron abundance and its physiological functions bring into question the ability of iron compounds at the same concentrations, on the one hand, to inhibit the microbial growth and, on the other hand, to positively affect mammalian cells. At present, multiple studies have been published that show the antimicrobial effect of IONPs against Gram-negative and Gram-positive bacteria and fungi. Several studies have established that IONPs have a low toxicity to eukaryotic cells. It gives hope that IONPs can be considered potential antimicrobial agents of the new generation that combine antimicrobial action and high biocompatibility with the human body. This review is intended to inform readers about the available data on the antimicrobial properties of IONPs, a range of susceptible bacteria, mechanisms of the antibacterial action, dependence of the antibacterial action of IONPs on the method for synthesis, and the biocompatibility of IONPs with eukaryotic cells and tissues.
    Keywords:  antimicrobial effect; green synthesis; iron oxide; nanoparticles
  2. Nat Methods. 2021 Aug;18(8): 945-952
      Acoustic reporter genes (ARGs) that encode air-filled gas vesicles enable ultrasound-based imaging of gene expression in genetically modified bacteria and mammalian cells, facilitating the study of cellular function in deep tissues. Despite the promise of this technology for biological research and potential clinical applications, the sensitivity with which ARG-expressing cells can be visualized is currently limited. Here we present burst ultrasound reconstructed with signal templates (BURST)-an ARG imaging paradigm that improves the cellular detection limit by more than 1,000-fold compared to conventional methods. BURST takes advantage of the unique temporal signal pattern produced by gas vesicles as they collapse under acoustic pressure above a threshold defined by the ARG. By extracting the unique pattern of this signal from total scattering, BURST boosts the sensitivity of ultrasound to image ARG-expressing cells, as demonstrated in vitro and in vivo in the mouse gastrointestinal tract and liver. Furthermore, in dilute cell suspensions, BURST imaging enables the detection of gene expression in individual bacteria and mammalian cells. The resulting abilities of BURST expand the potential use of ultrasound for non-invasive imaging of cellular functions.
  3. Molecules. 2021 Jul 29. pii: 4587. [Epub ahead of print]26(15):
      There is a challenging need for the development of new alternative nanostructures that can allow the coupling and/or encapsulation of therapeutic/diagnostic molecules while reducing their toxicity and improving their circulation and in-vivo targeting. Among the new materials using natural building blocks, peptides have attracted significant interest because of their simple structure, relative chemical and physical stability, diversity of sequences and forms, their easy functionalization with (bio)molecules and the possibility of synthesizing them in large quantities. A number of them have the ability to self-assemble into nanotubes, -spheres, -vesicles or -rods under mild conditions, which opens up new applications in biology and nanomedicine due to their intrinsic biocompatibility and biodegradability as well as their surface chemical reactivity via amino- and carboxyl groups. In order to obtain nanostructures suitable for biomedical applications, the structure, size, shape and surface chemistry of these nanoplatforms must be optimized. These properties depend directly on the nature and sequence of the amino acids that constitute them. It is therefore essential to control the order in which the amino acids are introduced during the synthesis of short peptide chains and to evaluate their in-vitro and in-vivo physico-chemical properties before testing them for biomedical applications. This review therefore focuses on the synthesis, functionalization and characterization of peptide sequences that can self-assemble to form nanostructures. The synthesis in batch or with new continuous flow and microflow techniques will be described and compared in terms of amino acids sequence, purification processes, functionalization or encapsulation of targeting ligands, imaging probes as well as therapeutic molecules. Their chemical and biological characterization will be presented to evaluate their purity, toxicity, biocompatibility and biodistribution, and some therapeutic properties in vitro and in vivo. Finally, their main applications in the biomedical field will be presented so as to highlight their importance and advantages over classical nanostructures.
    Keywords:  biomedical applications; flow chemistry; nanotheranostics; peptide self-assembly; peptide synthesis; physicochemical and biological characterization
  4. Nanomaterials (Basel). 2021 Jul 09. pii: 1796. [Epub ahead of print]11(7):
      A magnetic nanocomposite, consisting of Fe3O4 nanoparticles embedded into a Mg/Al layered double hydroxide (LDH) matrix, was developed for cancer multimodal therapy, based on the combination of local magnetic hyperthermia and thermally induced drug delivery. The synthesis procedure involves the sequential hydrolysis of iron salts (Fe2+, Fe3+) and Mg2+/Al3+ nitrates in a carbonate-rich mild alkaline environment followed by the loading of 5-fluorouracil, an anionic anticancer drug, in the interlayer LDH space. Magnetite nanoparticles with a diameter around 30 nm, dispersed in water, constitute the hyperthermia-active phase able to generate a specific loss of power of around 500 W/g-Fe in an alternating current (AC) magnetic field of 24 kA/m and 300 kHz as determined by AC magnetometry and calorimetric measurements. Heat transfer was found to trigger a very rapid release of drug which reached 80% of the loaded mass within 10 min exposure to the applied field. The potential of the Fe3O4/LDH nanocomposites as cancer treatment agents with minimum side-effects, owing to the exclusive presence of inorganic phases, was validated by cell internalization and toxicity assays.
    Keywords:  Fe3O4; cell internalization; continuous flow synthesis; drug delivery; layered double hydroxide; magnetic hyperthermia; nanocomposite
  5. Biomater Sci. 2021 Aug 05.
      There is a growing interest in magnetic nanocomposites in biomaterials science. In particular, nanocomposites that combine poly(lactide) (PLA) nanofibers and superparamagnetic iron oxide nanoparticles (SPIONs), which can be obtained by either electrospinning of a SPION suspension in PLA or by precipitating SPIONs at the surface of PLA, are well documented in the literature. However, these two classical processes yield nanocomposites with altered materials properties, and their long-term in vivo fate and performances have in most cases only been evaluated over short periods of time. Recently, we reported a new strategy to prepare well-defined PLA@SPION nanofibers with a quasi-monolayer of SPIONs anchored at the surface of PLA electrospun fibers. Herein, we report on a 6-month in vivo rat implantation study with the aim of evaluating the long-term magnetic resonance imaging (MRI) properties of this new class of magnetic nanocomposites, as well as their tissue integration and degradation. Using clinically relevant T2-weighted MRI conditions, we show that the PLA@SPION nanocomposites are clearly visible up to 6 months. We also evaluate here by histological analyses the slow degradation of the PLA@SPIONs, as well as their biocompatibility. Overall, these results make these nanocomposites attractive for the development of magnetic biomaterials for biomedical applications.
  6. Nanomaterials (Basel). 2021 Jul 09. pii: 1787. [Epub ahead of print]11(7):
      The design of novel multifunctional materials based on nanoparticles requires tuning of their magnetic properties, which are strongly dependent on the surface structure. The organic coating represents a unique tool to significantly modify the surface structure trough the bonds between the ligands of the organic molecule and the surface metal atoms. This work presents a critical overview of the effects of the organic coating on the magnetic properties of nanoparticles trough a selection of papers focused on different approaches to control the surface structure and the morphology of nanoparticles' assemblies.
    Keywords:  magnetic nanoparticles; magnetic properties; molecular coating
  7. Chem Sci. 2021 Jul 14. 12(27): 9458-9465
      The biomineralization of intracellular magnetite in magnetotactic bacteria (MTB) is an area of active investigation. Previous work has provided evidence that magnetite biomineralization begins with the formation of an amorphous phosphate-rich ferric hydroxide precursor phase followed by the eventual formation of magnetite within specialized vesicles (magnetosomes) through redox chemical reactions. Although important progress has been made in elucidating the different steps and possible precursor phases involved in the biomineralization process, many questions still remain. Here, we present a novel in vitro method to form magnetite directly from a mixed valence iron phosphate precursor, without the involvement of other known iron hydroxide precursors such as ferrihydrite. Our results corroborate the idea that phosphate containing phases likely play an iron storage role during magnetite biomineralization. Further, our results help elucidate the influence of phosphate ions on iron chemistry in groundwater and wastewater treatment.
  8. Nanomaterials (Basel). 2021 Jul 09. pii: 1788. [Epub ahead of print]11(7):
      The COVID-19 pandemic is currently an unprecedented public health threat. The rapid spread of infections has led to calls for alternative approaches to combat the virus. Nanotechnology is taking root against SARS-CoV-2 through prevention, diagnostics and treatment of infections. In light of the escalating demand for managing the pandemic, a comprehensive review that highlights the role of nanomaterials in the response to the pandemic is highly desirable. This review article comprehensively discusses the use of nanotechnology for COVID-19 based on three main categories: prevention, diagnostics and treatment. We first highlight the use of various nanomaterials including metal nanoparticles, carbon-based nanoparticles and magnetic nanoparticles for COVID-19. We critically review the benefits of nanomaterials along with their applications in personal protective equipment, vaccine development, diagnostic device fabrication and therapeutic approaches. The remaining key challenges and future directions of nanomaterials for COVID-19 are briefly discussed. This review is very informative and helpful in providing guidance for developing nanomaterial-based products to fight against COVID-19.
    Keywords:  COVID-19; diagnostics; nanomaterials; prevention; treatment
  9. Curr Pharm Des. 2021 Aug 03.
      With the worldwide increasing rate of chronic diseases, such as cancer, the development of novel techniques to improve the efficacy of therapeutic agents is highly demanded. Nanoparticles are especially well suited to encapsulate drugs and other therapeutic agents, bringing additional advantages, such as less frequent dosage requirements, reduced side effects due to specific targeting, and therefore increased patient compliance. However, with the increasing use of nanoparticles and their recent launch on the pharmaceutical market it is important to achieve high quality control of these advanced systems. In this review, we discuss the properties of different nanoparticles, the pharmacokinetics, the biosafety issues of concern, and conclude with novel nanotherapeutics and nanotheragnostics for cancer drug delivery.
    Keywords:  Nanomedicine; advanced drug delivery; cancer drug delivery; cancer nanotheragnostics; drug nanoparticles; nanosafety; nanotheragnostics; nanotherapeutics; pharmacokinetics
  10. Curr Pharm Des. 2021 Aug 03.
      Nanoparticles (NPs) as nanocarriers have emerged as novel and promising theranostic agents. The term theranostics revealed the properties of NPs capable of diagnosing the disease at an early stage and/or treating the disease. Such NPs are usually developed employing a surface engineering approach. The theranostic agents comprise NPs loaded with a drug/diagnostic agent that delivers it precisely to the target site. Theranostics is a field with promising results in enhancing therapeutic efficacy facilitated through higher payload at the targeted tissue, reduced dose, and dose-dependent side effects. However, controversies in terms of toxicity and size-dependent properties have often surfaced for NPs. Thus, a stringent in-vitro and in-vivo evaluation is required to develop safe and non-toxic NPs as theranostic agents. The review also focuses on the various entry points of NPs in the human system and their outcomes, including toxicity. It elaborates the evaluation criteria to ensure the safe use of NPs for diagnostic and therapeutic purposes.
    Keywords:  Nanoparticles; Pharmacokinetic; Theranostics; Toxicity
  11. Cells. 2021 Jul 06. pii: 1704. [Epub ahead of print]10(7):
      AFM-based rheology methods enable the investigation of the viscoelastic properties of cancer cells. Such properties are known to be essential for cell functions, especially for malignant cells. Here, the relevance of the force modulation method was investigated to characterize the viscoelasticity of bladder cancer cells of various invasiveness on soft substrates, revealing that the rheology parameters are a signature of malignancy. Furthermore, the collagen microenvironment affects the viscoelastic moduli of cancer cell spheroids; thus, collagen serves as a powerful proxy, leading to an increase of the dynamic moduli vs. frequency, as predicted by a double power law model. Taken together, these results shed new light on how cancer cells and tissues adapt their viscoelastic properties depending on their malignancy and the microenvironment. This method could be an attractive way to control their properties in the future, based on the similarity of spheroids with in vivo tumor models.
    Keywords:  AFM; cancer cells; confocal microscopy; microenvironment; rheology; spheroids
  12. Curr Opin Cell Biol. 2021 Jul 28. pii: S0955-0674(21)00075-2. [Epub ahead of print]72 81-90
      Collective behaviour emerges from interacting units within communities, such as migrating herds, swimming fish schools, and cells within tissues. At the microscopic level, collective behaviours include collective cell migration in development and cancer invasion, rhythmic gene expression in pattern formation, cell competition in homeostasis and cancer, force generation and mechano-sensing in morphogenesis. Studying the initiation and the maintenance of collective cell behaviours is key to understand the principles of development, regeneration and disease. However, the manifold influences of contributing factors in in vivo environments challenge the dissection of causalities in animal models. As an alternative model that has emerged to overcome this difficulty, in vitro three-dimensional organoid cultures provide a reductionist approach yet retain similarities with the in vivo tissue in cellular composition and tissue organisation. Here, we focus on recent progresses in studying collective behaviours in different organoid systems and discuss their advantages and the possibility of improvement for future applications.
    Keywords:  Cell competition; Cell migration; Collective behaviors; Mechanics; Organoids; Oscillation
  13. Macromol Biosci. 2021 Aug 06. e2100186
      Hydrogel is a kind of 3D polymer network with strong swelling ability in water and appropriate mechanical and biological properties, which make it feasible to maintain bioactive substances and has promising applications in the fields of biomaterials, soft machines, and artificial tissues. Unfortunately, traditional hydrogels prepared by chemical crosslinking have poor mechanical properties and limited functions, which limit their further application. In recent years, with the continuous development of nanoparticle research, more and more studies have combined nanoparticles with hydrogels to make up for the shortcomings of traditional hydrogels. In this article, the types and functions of hydrogels and nanomaterials are introduced first, as well as the functions and applications of injectable nanocomposite hydrogels (INHs), then the latest progress of INHs for cancer treatment is reviewed, some existing problems are summarized, and the application prospect of NHs is prospected.
    Keywords:  cancer therapy; injectable; nanocomposite hydrogel; nanomaterials
  14. Biotechnol J. 2021 Aug 05. e2100239
      Synthetic biology continues to progress by relying on more robust tools for transcriptional control, of which promoters are the most fundamental component. Numerous studies have sought to characterize promoter function, determine principles to guide their engineering, and create promoters with stronger expression or tailored inducible control. In this review, we will summarize promoter architecture and highlight recent advances in the field, focusing on the novel applications of inducible promoter design and engineering towards metabolic engineering and cellular therapeutic development. Additionally, we will highlight how the expansion of new, machine learning techniques for modeling and engineering promoter sequences are enabling more accurate prediction of promoter characteristics. This article is protected by copyright. All rights reserved.
    Keywords:  bacteria; bioinformatics; cellular engineering; computational biotechnology; gene expression; machine learning; metabolic engineering; promoter engineering; synthetic biology; transcription; yeast
  15. Rev Sci Instrum. 2021 Jul 01. 92(7): 074105
      Microbubbles (MBs) have a multitude of applications including as contrast agents in ultrasound imaging and as therapeutic drug delivery vehicles, with further scope for combining their diagnostic and therapeutic properties (known as theranostics). MBs used clinically are commonly made by mechanical agitation or sonication methods, which offer little control over population size and dispersity. Furthermore, clinically used MBs are yet to be used therapeutically and further research is needed to develop these theranostic agents. In this paper, we present our MB production instrument "Horizon," which is a robust, portable, and user-friendly instrument, integrating the key components for producing MBs using microfluidic flow-focusing devices. In addition, we present the system design and specifications of Horizon and the optimized protocols that have so far been used to produce MBs with specific properties. These include MBs with tailored size and low dispersity (monodisperse); MBs with a diameter of ∼2 μm, which are more disperse but also produced in higher concentration; nanobubbles with diameters of 100-600 nm; and therapeutic MBs with drug payloads for targeted delivery. Multiplexed chips were able to improve production rates up to 16-fold while maintaining production stability. This work shows that Horizon is a versatile instrument with potential for mass production and use across many research facilities, which could begin to bridge the gap between therapeutic MB research and clinical use.