bims-mricoa Biomed News
on MRI contrast agents
Issue of 2022–01–16
eight papers selected by
Merve Yavuz, Bilkent University



  1. ACS Appl Bio Mater. 2020 Dec 21. 3(12): 8172-8187
      The positive response of superparamagnetic iron oxide nanoparticles (SPIONs), in terms of biodegradability, circulation, elimination, toxicity, and manipulation of their structure/activity relationship, has enabled them to find their way into commercialization as an iron supplement, MRI contrast agents, MPI tracers, and hyperthermia and magneto-mechanical actuators. This Review focuses on the most current progress regarding the application of SPIONs as magnetic therapeutic agents for cancer treatment and tissue engineering. Because of their superior magnetic anisotropy, irreversibility of high- and low-field magnetization, and superparamagnetic ordering at corporal temperatures, they exhibit the unique ability to respond to theraputic doses (e.g., in magnetic hyperthermia and targeted drug delivery). This Review discusses the role of SPIONs to enhance chemotherapy and radiotherapy efficiency and specificity and how this enhancement could mitigate some side effects. SPIONs applied as tools for gene delivery, immunotherapy, and tissue engineering are also reviewed in the context of their potential to translational medicine. Lastly, some emerging issues concerning SPION toxicity are summarized and how they are being addressed to achieve success in clinical applications is discussed.
    Keywords:  cancer nanotechnology; chemotherapy; hyperthermia; iron oxide nanoparticles; magnetic therapy; magneto-mechanical actuation; radiotherapy
    DOI:  https://doi.org/10.1021/acsabm.0c00947
  2. ACS Appl Bio Mater. 2020 Apr 20. 3(4): 2305-2313
      Elevating and monitoring the temperature of tumors using magnetic nanoparticles (MNPs) still presents a challenge in magnetic hyperthermia therapy. The efficient heating of tumor volume can be achieved by preparing MNPs with high magnetization values. The next-generation approach to magnetic resonance image (MRI)-guided magneto-chemotherapy of cancer based on high-magnetic-moment iron oxide nanoparticles is proposed. The proof of concept is validated by cellular MRI experiments on breast cancer cells. To explore magneto-chemotherapy, we developed high-magnetic-moment iron oxide (Fe3O4) nanoparticles (NPs) using base diisopropylamine (DIPA), which plays a dual role as reducing agent and surface stabilizer. Spherical NPs with ∼12 nm size and a high magnetization value of about 92 emu g-1 at room temperature are obtained by this unique method. A high specific absorption rate value of ∼717 wg-1 was obtained for Fe3O4 NPs in water at an alternating magnetic field of 20 kAm-1 and frequency of 267 kHz, which is attributed to the high magnetization value. The magneto-polymeric micelle structure is formed by using Pluronic F127, and anticancer drug doxorubicin is conjugated in the micelle by electrostatic interactions for magneto-chemotherapy. Finally, the magnetic resonance imaging (MRI)-guided magneto-chemotherapy was achieved on breast cancer (MCF7) cells with an overall ∼96% killing of cancer cells attained in 30 min of magneto-chmeotherapy.
    Keywords:  induction heating properties; iron oxide nanoparticles; magnetic properties; nanofluids; specific absorption rate
    DOI:  https://doi.org/10.1021/acsabm.0c00077
  3. ACS Appl Bio Mater. 2020 Dec 21. 3(12): 8136-8145
      Bacteria possess many unique properties in treating cancer that are unachievable with standard methods, including specific tumor targeting, deep tissue penetration, and programmable therapeutic efficacy. Bacteria species such as Salmonella, Escherichia, Clostridium, and Listeria have been demonstrated to restrict tumor growth with improved prognosis in mice models. Moreover, some bacterial strains were advanced to clinical trials. This Spotlight on Applications summarizes general strategies for engineering living bacteria to fight cancer and provides examples to illustrate different approaches to engineer bacteria for safety and therapeutic index improvement.
    Keywords:  bacteria engineering; bacteria modification; cancer therapy; living bacteria; synergic therapy; tumor
    DOI:  https://doi.org/10.1021/acsabm.0c01286
  4. ACS Appl Bio Mater. 2020 Feb 17. 3(2): 1061-1070
      The antimicrobial capability and recyclability of two conjugates that combines the versatility of iron oxide magnetic nanoparticles (MNPs) with the high photosensitizing proficiency of boron-dipyrromethene (BODIPY) dyes are assessed. By a relatively simple synthetic pathway, two conjugates were obtained. The first one, MNP-B1, contains a highly fluorescent dye for bioimaging and suitable inactivating properties. The other one, MNP-B2, is optimized to improve the production of cytotoxic reactive oxygen species (ROS) by incorporating heavy atoms in the BODIPY core. In vitro experiments in bacterial cell suspensions and at the single bacterium level reveal that both conjugates can inactivate either Gram-positive (methicillin-resistant Staphylococcus aureus) and Gram-negative (Escherichia coli) bacteria. By means of fluorescence microscopy, not only cellular uptake of the conjugates but also recyclability and sustained performance over the cycles of photodynamic inactivation (PDI) are demonstrated. This is the first time that MNPs functionalized with BODIPY dyes are utilized to obtain fluorescent images of bacterial cells and photoinactivate pathogens.
    Keywords:  BODIPY; bioimaging; magnetic nanoparticles; photodynamic inactivation; photosensitizer
    DOI:  https://doi.org/10.1021/acsabm.9b01035
  5. Nanomaterials (Basel). 2021 Dec 31. pii: 130. [Epub ahead of print]12(1):
      Nanotechnology is a booming avenue in science and has a multitude of applications in health, agriculture, and industry. It exploits materials' size at nanoscale (1-100 nm) known as nanoparticles (NPs). These nanoscale constituents are made via chemical, physical, and biological methods; however, the biological approach offers multiple benefits over the other counterparts. This method utilizes various biological resources for synthesis (microbes, plants, and others), which act as a reducing and capping agent. Among these sources, microbes provide an excellent platform for synthesis and have been recently exploited in the synthesis of various metallic NPs, in particular iron. Owing to their biocompatible nature, superparamagnetic properties, small size efficient, permeability, and absorption, they have become an integral part of biomedical research. This review focuses on microbial synthesis of iron oxide nanoparticles using various species of bacteria, fungi, and yeast. Possible applications and challenges that need to be addressed have also been discussed in the review; in particular, their antimicrobial and anticancer potentials are discussed in detail along with possible mechanisms. Moreover, some other possible biomedical applications are also highlighted. Although iron oxide nanoparticles have revolutionized biomedical research, issues such as cytotoxicity and biodegradability are still a major bottleneck in the commercialization of these nanoparticle-based products. Addressing these issues should be the topmost priority so that the biomedical industry can reap maximum benefit from iron oxide nanoparticle-based products.
    Keywords:  anticancer; antimicrobial; green synthesis; iron oxide; nanoparticles
    DOI:  https://doi.org/10.3390/nano12010130
  6. Nanomaterials (Basel). 2021 Dec 23. pii: 38. [Epub ahead of print]12(1):
      Magnetic nanoparticles (MNPs) are widely considered for cancer treatment, in particular for magnetic hyperthermia (MHT). Thereby, MNPs are still being optimized for lowest possible toxicity on organisms while the magnetic properties are matched for best heating capabilities. In this study, the biocompatibility of 12 nm cobalt ferrite MNPs, functionalized with citrate ions, in different dosages on mice and rats of both sexes was investigated for 30 days after intraperitoneal injection. The animals' weight, behavior, and blood cells changes, as well as blood biochemical parameters are correlated to histological examination of organs revealing that cobalt ferrite MNPs do not have toxic effects at concentrations close to those used previously for efficient MHT. Moreover, these MNPs demonstrated high specific loss power (SLP) of about 400 W g-1. Importantly the MNPs retained their magnetic properties inside tumor tissue after intratumoral administration for several MHT cycles within three days. Thus, cobalt ferrite MNPs represent a perspective platform for tumor therapy by MHT due to their ability to provide effective heating without exerting a toxic effect on the organism. This opens up new avenues for smaller MNPs sizes while their heating efficiency is maintained.
    Keywords:  biocompatibility; cobalt ferrite nanoparticles; controlled magnetic hyperthermia; magnetic properties; tumor therapy
    DOI:  https://doi.org/10.3390/nano12010038
  7. ACS Appl Bio Mater. 2021 May 17. 4(5): 4039-4048
      A biomolecule-guided self-assembly is a powerful approach to systematically organize diverse inorganic nanoparticles into predefined nanostructures in multiple dimensions. A class of supramolecular proteins is one kind of such biomolecules natively possessing exquisite structures and modifiable ligands, providing a desired candidate for templating functional nanoparticles. Indeed, protein-based assembly of nano-objects has been emerging as one of the ideal routes to fabricate precise architectures. Here, we briefly summarize recent works of well-organized nanoparticle structures templated by individual proteins or highly ordered protein assemblies. The functionalization of protein templates and control over the interactions between nanoparticles and templates are highlighted. Finally, current challenges and future directions are discussed in the design of complicated protein-based materials.
    Keywords:  metallic nanoparticle; nanostructure; protein functionalization; protein template; self-assembly
    DOI:  https://doi.org/10.1021/acsabm.1c00156
  8. ACS Appl Bio Mater. 2020 Apr 20. 3(4): 2401-2409
      Although nowadays there is a renewed and growing interest in Mn-based contrast agents, there are only few studies dealing with Mn-based lipophilic nanoparticles and how they may be optimized as MRI contrast agents. Three amphiphilic paramagnetic Mn(II) complexes based on derivatives of EDTA and 1,4-DO2A were used for the preparation of lipidic nanoparticles. The length and position of the aliphatic chains were found to control whether either vesicular liposomes, nonvesicular bicelles, or a mixture of both was produced as well as the size and morphology of phospholipid-based self-assembling nanoaggregates. These differences determine whether hydrophilic Gd-based contrast agents or fluorescent dyes can be entrapped in the aqueous core of the nanoaggregate. Structural characterization was performed by cryo-TEM. Detailed 1H NMR relaxometric analyses were carried out on all systems. The effect of entrapping gadoteridol in the aqueous core (where present) was studied by preparing diamagnetic amphiphilic Zn(II) analogues. In the case of homogeneous systems, the data were also fitted to obtain the relaxometric parameters for comparison with literature data. The results of these studies demonstrate enhanced relaxivity of the nanoaggregates with respect to monomeric analogues. This work allowed us to understand how to control the formation of different types of nanovesicles (liposomes, bicelles, and micelles), optimize their MRI contrast, and provide different in vivo biodistribution characteristics.
    Keywords:  amphiphilic chelating ligands; liposomes; manganese; nanoparticles; relaxometry
    DOI:  https://doi.org/10.1021/acsabm.0c00138