bims-mricoa Biomed News
on MRI contrast agents
Issue of 2021–07–11
eight papers selected by
Merve Yavuz, Bilkent University



  1. Curr Top Med Chem. 2021 Jul 01.
      Nanotechnology has shown promising advancements in the field of drug development and its delivery. In particular, the applications of nanoparticles for treatment and diagnostics of cancer reached such a precision that it can detect a single cancer cell and can target it to deliver a payload for the treatment of that cancerous cell. Conventional cancer therapy methods have side effects, and diagnostics techniques are time-consuming and expensive. Nanoparticles (NPs) such as polymeric nanoparticles (nanogels, nanofibers, liposomes), metallic nanoparticles such as gold NP (GNPs), sliver NP (AgNP), calcium nanoparticles (CaNPs), carbon nanotubes (CNTs), graphene, and quantum dots (QDs) have revolutionized cancer diagnostics and treatments due to their high surface charge, size and morphology. Functionalization of these nanoparticles with different biological molecules, such as antibodies, helps them to targeted the delivery and early detection of cancer cells through their plasmon resonance properties. While some of the magnetic properties of nanoparticles such as iron (Fe), copper (Cu), and carbon NT were also evaluated for detection and treatments of cancer cells. An advanced type of nanoparticles, such as nanobubbles and oxygen-releasing polymers, are helping to address the hypoxia conditions in the cancer microenvironment, while others are employed in photodynamic therapy (PDT) and photothermal therapy (PTT) due to their intrinsic theranostic properties. The green synthesis of nanoparticles has further increased biocompatibility and broadened their applications. In this review paper, we discussed the advancement in nanotechnology and its applications for cancer treatment and diagnostics and highlighted challenges for translation of these advanced nano-based techniques for clinical applications and their green synthesis.
    Keywords:  Cancer; Conventional Therapy; Diagnostics; Green synthesis; Metallic nanoparticles; Targeted delivery
    DOI:  https://doi.org/10.2174/1568026621666210701144124
  2. J Mater Chem B. 2021 Jul 06.
      Hepatocellular carcinoma has become one of the most prevalent cancers, with a high mortality rate. Accurate diagnosis at an earlier stage is regarded as an effective measure to reduce the disease-related mortality of liver cancer. Magnetic resonance imaging (MRI) as a non-invasive checking mode has become a powerful tool in medical diagnosis. However, MRI contrast agents for liver-specific imaging either have some side effects or the imaging effect is not ideal. Thus, development of more efficient and security MRI contrast agents for the early diagnosis of hepatocellular carcinoma is urgent. Herein, a kind of water-soluble gadofullerene nanoparticle (GFNP) with high efficiency and security has been successfully used to achieve in situ liver cancer imaging. By comparing GFNPs with different functional groups, Gd@C82 modified by a hydroxyl group (GF-OH) presents the highest contrast efficiency both in vitro and in vivo. Notably, the smallest tumor with a diameter of only 0.5 mm could be clearly observed by GF-OH using MRI. Moreover, the imaging window of GF-OH is more than 3-6 hours. In addition, GF-OH can be mostly excreted from the living body and causes no serious toxicity. These results demonstrate that GF-OH is a safe, efficient MRI contrast agent for the diagnosis of early orthotopic hepatocellular carcinoma.
    DOI:  https://doi.org/10.1039/d1tb00931a
  3. Plant Cell Physiol. 2021 Jul 08. pii: pcab104. [Epub ahead of print]
      Fluorescent probes are a powerful tool for visualizing cellular and subcellular structures, their dynamics, and cellular molecules in living cells, and enables us to monitor cellular processes in a spatio-temporal manner within complex and crowded systems. In addition to popular fluorescent proteins, a wide variety of small-molecule dyes have been synthesized through close association with the interdisciplinary field of chemistry and biology, ranging from those suitable for labeling cellular compartments such as organelles to those for labeling intracellular biochemical and biophysical processes and signaling. In recent years, self-labeling technologies including the SNAP-tag system have allowed us to attach these dyes to cellular domains or specific proteins, and are beginning to be employed in plant studies. In this mini review, we will discuss the current range of synthetic fluorescent probes that have been exploited for live cell imaging and the recent advances in the application that enable genetical tagging of synthetic probes in plant research.
    Keywords:  Fluorescent probes; Live cell imaging; SNAP-tag; Self-labeling protein tag; Synthetic dyes
    DOI:  https://doi.org/10.1093/pcp/pcab104
  4. Methods Mol Biol. 2021 ;2312 253-276
      Recent studies revealed the biological significance of dynamic multicomponent assemblies of biomolecules inside living cells. Protein and nucleic acid assemblies are biomolecular condensates or non-membrane-bound organelles that have attracted increasing attention. Synthetic tools that manipulate the dynamic assembly/disassembly process of the structures are useful in elucidating both biophysical mechanisms of their assembly/disassembly and physiological roles of the condensates. In this report, general protocols to form and observe synthetic polymer-based condensates in living cells are described using the tool iPOLYMER. Taking advantage of the modular design of the tool, both chemical and light stimuli can induce formation of synthetic condensates inside living cells, which are observed by laser-scanning confocal microscopy. The experimental design described herein should help those who conduct experiments on synthetic manipulation of biomolecular condensates using iPOLYMER and other tools for synthetic manipulation of condensates. Technical notes for using iPOLYMER, including basic protocols of chemical- or light-inducible dimerization techniques (CID/LID), choice of proper control experiments, and advantages/disadvantages are also presented.
    Keywords:  Biomolecular condensates; Hydrogel; Inducible dimerization; Stress granules; Synthetic biology; iPOLYMER
    DOI:  https://doi.org/10.1007/978-1-0716-1441-9_15
  5. Soft Matter. 2021 Jul 09.
      Viscous environments are ubiquitous in nature and in engineering applications, from mucus in lungs to oil recovery strategies in the earth's subsurface - and in all these environments, bacteria also thrive. The behavior of bacteria in viscous environments has been investigated for a single bacterium, but not for active suspensions. Dense populations of pusher-type bacteria are known to create superfluidic regimes where the effective viscosity of the entire suspension is reduced through collective motion, and the main purpose of this study is to investigate how a viscous environment will affect this behavior. Using a Couette rheometer, we measure shear stress as a function of the applied shear rate to define the effective viscosity of suspensions of Escherichia coli (E. coli), while varying both the bacterial density within the suspension and the viscosity of the suspending fluid. We document the remarkable observation that E. coli decreases the effective suspension viscosity to near-zero (superfluidic regime) for all solvent viscosities tested (1-17 mPa s). Specifically, we observe that the bacterial density needed to trigger this superfluidic regime and the maximum shear rate under which this regime can be sustained both decrease with increasing solvent viscosity. We find that the resulting rheograms can be well approximated by the Carreau-Yasuda law. Using this, we propose a constitutive model as a function of the solvent viscosity and the bacterial concentration only. This model captures the onset of the superfluidic regime and offers promising avenues for the modelling of flow of bacterial suspensions in viscous environments.
    DOI:  https://doi.org/10.1039/d1sm00243k
  6. Mater Sci Eng C Mater Biol Appl. 2021 Aug;pii: S0928-4931(21)00389-1. [Epub ahead of print]127 112249
      Optical biosensors show attractive performance in medical sensing in the event of using different nanoparticles in their design. Owing to their unique optical characteristics and biological compatibility, gold nanoparticles (GNPs), silver nanoparticles (AgNPs), bimetallic nanoparticles and magnetic nanoparticles have been broadly implemented in making sensing tools. The functionalization of these nanoparticles with different components provides an excellent opportunity to assemble selective and sensitive sensing materials to detect various biological molecules related to breast cancer. This review summarizes the recent application of optical biosensing devices based on nanomaterials and discusses their pros and cons to improve breast cancer detection in real samples. In particular, the main constituent elements of these optical biosensors including recognition and transducer elements, types of applied nanostructures, analytical sensing procedures, sensor detection ranges and limit of detection (LOD), are expressed in detail.
    Keywords:  Breast cancer; Gold nanoparticles; Magnetic nanoparticles; Metallic nanoparticles; Optical biosensors; Silver nanoparticles
    DOI:  https://doi.org/10.1016/j.msec.2021.112249
  7. Front Oncol. 2021 ;11 593996
       Purpose: To validate the feasibility of using peri-tumoral radiofrequency hyperthermia (RFH)-enhanced chemotherapy to obliterate hepatic tumor margins.
    Method and Materials: This study included in vitro experiments with VX2 tumor cells and in vivo validation experiments using rabbit models of liver VX2 tumors. Both in vitro and in vivo experiments received different treatments in four groups (n=6/group): (i) RFH-enhanced chemotherapy consisting of peri-tumoral injection of doxorubicin plus RFH at 42°C; (ii) RFH alone; (iii) doxorubicin alone; and (iv) saline. Therapeutic effect on cells was evaluated using different laboratory examinations. For in vivo experiments, orthotopic hepatic VX2 tumors in 24 rabbits were treated by using a multipolar radiofrequency ablation electrode, enabling simultaneous delivery of both doxorubicin and RFH within the tumor margins. Ultrasound imaging was used to follow tumor growth overtime, correlated with subsequent histopathological analysis.
    Results: In in vitro experiments, MTS assay demonstrated the lowest cell proliferation, and apoptosis analysis showed the highest apoptotic index with RFH-enhanced chemotherapy, compared with the other three groups (p<0.01). In in vivo experiments, ultrasound imaging detected the smallest relative tumor volume with RFH-enhanced chemotherapy (p<0.01). The TUNEL assay further confirmed the significantly increased apoptotic index and decreased cell proliferation in the RFH-enhanced therapy group (p<0.01).
    Conclusion: This study demonstrates that peri-tumoral RFH can specifically enhance the destruction of tumor margins in combination with peri-tumoral injection of a chemotherapeutic agent. This new interventional oncology technique may address the critical clinical problem of frequent marginal tumor recurrence/persistence following thermal ablation of large (>3 cm) hepatic cancers.
    Keywords:  chemotherapy; image-guided interventional oncology; liver malignancies; peri-tumoral injection; radiofrequency hyperthermia
    DOI:  https://doi.org/10.3389/fonc.2021.593996
  8. Int J Nanomedicine. 2021 ;16 4351-4369
       Purpose: Multifunctional nanoparticles with targeted therapeutic function and diagnostic-imaging are of great interest in the domain of precision therapy. NIR laser responsive nanoparticles (PLGA-PEG-FA encapsulating Bi2S3, PFP, and Dox (designed as FBPD NPs)) are synthesized for ovarian cancer targeted combination therapy with CT/PA dual-modal imaging guidance (PA: photoacoustic; CT: X-ray computed tomography).
    Methods and Results: The FBPD NPS prepared by the double emulsification method revealed excellent dispersity, great stability, outstanding optical properties. The temperature of FBPD NPs increased rapidly after laser irradiation, inducing liquid-to-gas conversion of perfluoropentane (PFP), and promoting the release of Dox up to 86.7%. These FBPD NPs demonstrated their outstanding imaging capability for both PA and CT imaging both in vitro and in vivo, providing the potential for therapeutic guidance and monitoring. Assisted by folic acid, these nanoparticles could highly enrich in ovarian tumor tissue and the accumulation peaked at 3 h after intravenous administration. The desirable photothermal-conversion efficiency of the nanoparticles combined with chemotherapy achieved highly efficient therapy, which was demonstrated both in vitro and in vivo.
    Conclusion: We successfully constructed multifunctional theranostic FBPD NPs for highly efficient PTT/chemotherapy combined therapy with dual CT/PA imaging guidance/monitoring. The unique nanoparticles with multiple abilities pave an emerging way toward precise treatment of ovarian cancer.
    Keywords:  bismuth sulfide; chemotherapy; folic acid; photothermal therapy
    DOI:  https://doi.org/10.2147/IJN.S299376