bims-mricoa 2021-07-25 papers

bims-mricoa

Biomed News

on MRI contrast agents

Issue of 2021–07–25
thirteen papers selected by
Merve Yavuz, Bilkent University

Ultrasmall superparamagnetic iron oxide nanoparticles: A next generation contrast agent for magnetic resonance imaging.
Iron oxide nanoparticles for immune cell labeling and cancer immunotherapy.
Development and evaluation of a multi-functional organic-inorganic nanotheranostic hybrid for pancreatic cancer therapy.
Microbial-based cancer therapy-bugs as drugs: History & the essential role of medical imaging.
Magnetothermal regulation of in vivo protein corona formation on magnetic nanoparticles for improved cancer nanotherapy.
Mechanisms of Drug Resistance and Use of Nanoparticle Delivery to Overcome Resistance in Breast Cancers.
Magnetic Particle Imaging: Current and Future Applications, Magnetic Nanoparticle Synthesis Methods and Safety Measures.
Effects of Gadolinium Deposits in the Cerebellum: Reviewing the Literature from In Vitro Laboratory Studies to In Vivo Human Investigations.
Agarose Micro-Well Platform for Rapid Generation of Homogenous 3D Tumor Spheroids.
Reactive oxygen species in cancer: current findings and future directions.
High-Yield Production, Characterization, and Functionalization of Recombinant Magnetosomes in the Synthetic Bacterium Rhodospirillum rubrum "magneticum".
Colorectal cancer treatment using bacteria: focus on molecular mechanisms.
Hypoxia-Overcoming Breast-Conserving Treatment by Magnetothermodynamic Implant for a Localized Free-Radical Burst Combined with Hyperthermia.

Wiley Interdiscip Rev Nanomed Nanobiotechnol. 2021 Jul 23. e1740

Ultrasmall superparamagnetic iron oxide nanoparticles: A next generation contrast agent for magnetic resonance imaging.

Can Chen, Jianxian Ge, Yun Gao, Lei Chen, Jiabin Cui, Jianfeng Zeng, Mingyuan Gao.

  As a research hotspot, the development of magnetic resonance imaging (MRI) contrast agents has attracted great attention over the past decades for improving the accuracy of diagnosis. Ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles with core diameter smaller than 5.0 nm are expected to become a next generation of contrast agents owing to their excellent MRI performance, long blood circulation time upon proper surface modification, renal clearance capacity, and remarkable biosafety profile. On top of these merits, USPIO nanoparticles are used for developing not only T1 contrast agents, but also T2 /T1 switchable contrast agents via assembly/disassembly approaches. In recent years, as a new type of contrast agents, USPIO nanoparticles have shown considerable applications in the diagnosis of various diseases such as vascular pathological changes and inflammations apart from malignant tumors. In this review, we are focusing on the state-of-the-art developments and the latest applications of USPIO nanoparticles as MRI contrast agents to discuss their advantages and future prospects. This article is categorized under: Diagnostic Tools > In Vivo Nanodiagnostics and Imaging.

Keywords:  contrast agents; iron oxide nanoparticles; magnetic resonance imaging; ultrasmall

DOI:  https://doi.org/10.1002/wnan.1740
Nanoscale Horiz. 2021 Jul 20.

Iron oxide nanoparticles for immune cell labeling and cancer immunotherapy.

Seokhwan Chung, Richard A Revia, Miqin Zhang.

Cancer immunotherapy is a novel approach to cancer treatment that leverages components of the immune system as opposed to chemotherapeutics or radiation. Cell migration is an integral process in a therapeutic immune response, and the ability to track and image the migration of immune cells in vivo allows for better characterization of the disease and monitoring of the therapeutic outcomes. Iron oxide nanoparticles (IONPs) are promising candidates for use in immunotherapy as they are biocompatible, have flexible surface chemistry, and display magnetic properties that may be used in contrast-enhanced magnetic resonance imaging (MRI). In this review, advances in application of IONPs in cell tracking and cancer immunotherapy are presented. Following a brief overview of the cancer immunity cycle, developments in labeling and tracking various immune cells using IONPs are highlighted. We also discuss factors that influence the effectiveness of IONPs as MRI contrast agents. Finally, we outline different approaches for cancer immunotherapy and highlight current efforts that utilize IONPs to stimulate immune cells to enhance their activity and response to cancer.

DOI: https://doi.org/10.1039/d1nh00179e
Biomed Mater. 2021 Jul 23.

Development and evaluation of a multi-functional organic-inorganic nanotheranostic hybrid for pancreatic cancer therapy.

Karolyn Infanta David, Ravikumar T S, Swaminathan Sethuraman, Krishnan Uma Maheswari.

  Pancreatic cancer is a fatal disease with poor survival rates. The high mortality associated with pancreatic cancer arises due to a combination of late diagnosis, multi-drug resistance, invasiveness of the cancer and the existence of a stromal barrier that restricts the access of the chemotherapeutic agent to the cancer cells. Smart nanocarriers that not only deliver the therapeutic agent in to the cancer tissue as well as enable imaging of the tissue represent an emerging paradigm in cancer therapy. Accurate and reliable detection of cancerous lesions in pancreas is essential for designing appropriate therapeutic strategy to annihilate the highly aggressive pancreatic cancer. A combination of imaging modalities can enhance the reliability of cancer detection. In this context, we report here a hybrid iron oxide-gold nanoparticle with contrast enhancing ability both in magnetic resonance imaging (MRI) and micro-computed tomography (micro-CT) that is co-encapsulated with the nucleotide analogue gemcitabine in a chitosan matrix. The theranostic system displayed enhanced cytotoxicity in PanC-1 pancreatic cancer cells when compared to normal cells over 48h due to differences in cell internalization. Further, the magnetocaloric effect of the iron oxide enabled faster release of the chemotherapeutic agent as well as augmented the cytotoxicity by inducing hyperthermia.

Keywords:  Nanotheranostic system; Pancreatic cancer,; chitosan nanoparticles; hybrid contrast enhancer

DOI:  https://doi.org/10.1088/1748-605X/ac177c
Cancer Treat Res Commun. 2021 Jul 14. pii: S2468-2942(21)00134-9. [Epub ahead of print]28 100436

Microbial-based cancer therapy-bugs as drugs: History & the essential role of medical imaging.

Hongxiu Ji, Xiaoming Yang.

  Microbial-based cancer therapy aims to use tumor-specific infectious microbes to fulfill the unmet medical needs for patients with difficult-to-treat malignancies. The NIH is calling to revisit the old concept from new perspectives, by incorporating advances in science and technology, to establish an alternative to the traditional categories of cancer managements. Medical imaging offers unique insight into the mechanisms of action, assessment of success/failure, and advantages/pitfalls of microbial-based cancer therapy, which in turn should facilitate the advances of this new initiative in modern medical oncology.

Keywords:  Medical history; Medical imaging; Microbial-based cancer therapy

DOI:  https://doi.org/10.1016/j.ctarc.2021.100436
Biomaterials. 2021 Jul 10. pii: S0142-9612(21)00377-X. [Epub ahead of print]276 121021

Magnetothermal regulation of in vivo protein corona formation on magnetic nanoparticles for improved cancer nanotherapy.

Tingbin Zhang, Galong Li, Yuqing Miao, Junjie Lu, Ningqiang Gong, Yifan Zhang, Yuantai Sun, Yuan He, Mingli Peng, Xiaoli Liu, Xing-Jie Liang, Haiming Fan.

  Engineering the protein corona (PC) on nanodrugs is emerging as an effective approach to improve their pharmacokinetics and therapeutic efficacy, but conventional in vitro pre-programmed methods have shown great limitation for regulation of the PC in the complex and dynamic in vivo physiological environment. Here, we demonstrate an magnetothermal regulation approach that allows us to in situ modulate the in vivo PC composition on iron oxide nanoparticles for improved cancer nanotherapy. Experimental results revealed that the relative levels of major opsonins and dysopsonins in the PC can be tuned quantitatively by means of heat induction mediated by the nanoparticles under an alternating magnetic field. When the PC was magnetically optimized in vivo, the nanoparticles exhibited prolonged circulation and enhanced tumor delivery efficiency in mice, 2.53-fold and 2.02-fold higher respectively than the control. This led to a superior thermotherapeutic efficacy of systemically delivered nanoparticles. In vivo magnetothermal regulation of the PC on nanodrugs will find wide applications in biomedicine.

Keywords:  In vivo magnetothermal regulation; Magnetic nanodrug; Pharmacokinetic behavior; Protein corona; Tumor delivery

DOI:  https://doi.org/10.1016/j.biomaterials.2021.121021
Adv Exp Med Biol. 2021 Jul 22.

Mechanisms of Drug Resistance and Use of Nanoparticle Delivery to Overcome Resistance in Breast Cancers.

Huseyin Beyaz, Hasan Uludag, Doga Kavaz, Nahit Rizaner.

  Breast cancer is the leading cancer type diagnosed among women in the world. Unfortunately, drug resistance to current breast cancer chemotherapeutics remains the main challenge for a higher survival rate. The recent progress in the nanoparticle platforms and distinct features of nanoparticles that enhance the efficacy of therapeutic agents, such as improved delivery efficacy, increased intracellular cytotoxicity, and reduced side effects, hold great promise to overcome the observed drug resistance. Currently, multifaceted investigations are probing the resistance mechanisms associated with clinical drugs, and identifying new breast cancer-associated molecular targets that may lead to improved therapeutic approaches with the nanoparticle platforms. Nanoparticle platforms including siRNA, antibody-specific targeting and the role of nanoparticles in cellular processes and their effect on breast cancer were discussed in this article.

Keywords:  Breast cancer; Drug resistance; Therapeutic targets/delivery (new discoveries)

DOI:  https://doi.org/10.1007/5584_2021_648
Int J Mol Sci. 2021 Jul 17. pii: 7651. [Epub ahead of print]22(14):

Magnetic Particle Imaging: Current and Future Applications, Magnetic Nanoparticle Synthesis Methods and Safety Measures.

Caroline Billings, Mitchell Langley, Gavin Warrington, Farzin Mashali, Jacqueline Anne Johnson.

  Magnetic nanoparticles (MNPs) have a wide range of applications; an area of particular interest is magnetic particle imaging (MPI). MPI is an imaging modality that utilizes superparamagnetic iron oxide particles (SPIONs) as tracer particles to produce highly sensitive and specific images in a broad range of applications, including cardiovascular, neuroimaging, tumor imaging, magnetic hyperthermia and cellular tracking. While there are hurdles to overcome, including accessibility of products, and an understanding of safety and toxicity profiles, MPI has the potential to revolutionize research and clinical biomedical imaging. This review will explore a brief history of MPI, MNP synthesis methods, current and future applications, and safety concerns associated with this newly emerging imaging modality.

Keywords:  magnetic nanoparticles; magnetic particle imaging; nanoparticle safety; superparamagnetic iron oxide

DOI:  https://doi.org/10.3390/ijms22147651
Int J Environ Res Public Health. 2021 Jul 06. pii: 7214. [Epub ahead of print]18(14):

Effects of Gadolinium Deposits in the Cerebellum: Reviewing the Literature from In Vitro Laboratory Studies to In Vivo Human Investigations.

Miski Aghnia Khairinisa, Winda Ariyani, Yoshito Tsushima, Noriyuki Koibuchi.

  Gadolinium (Gd)-based contrast agents (GBCAs) are chemicals injected intravenously during magnetic resonance imaging (MRI) to enhance the diagnostic yield. The repeated use of GBCAs can cause their deposition in the brain, including the cerebellum. Such deposition may affect various cell subsets in the brain and consequently cause behavioral alterations due to neurotoxicity. Caution should thus be exercised in using these agents, particularly in patients who are more likely to have repeated enhanced MRIs during their lifespan. Further studies are required to clarify the toxicity of GBCAs, and potential mechanisms causing neurotoxicity have recently been reported. This review introduces the effects of GBCAs in the cerebellum obtained from in vitro and in vivo studies and considers the possible mechanisms of neurotoxicity involved.

Keywords:  cerebellar development; gadolinium; neurotoxicity; thyroid hormone

DOI:  https://doi.org/10.3390/ijerph18147214
Curr Protoc. 2021 Jul;1(7): e199

Agarose Micro-Well Platform for Rapid Generation of Homogenous 3D Tumor Spheroids.

Mena Asha Krishnan, Kratika Yadav, Venkatesh Chelvam.

  In recent years, 3D culture of tumor spheroids has managed to revolutionize cancer research and drug discovery. 2D monolayer cells grown in cell culture flasks undergo radical changes in cell behavior, structure, and function owing to varying environmental cues and are unable to provide predictive data for preclinical evaluation. 3D tumor spheroids can better recapitulate tumor architecture, cell-cell and cell-matrix connectivity, and the tissue complexity of tumors grown in animal models. However, many of the existing techniques to culture 3D spheroids are time-consuming and ineffective and produce irregular-shaped spheroids that cannot be easily incorporated in biological assays. The set of protocols described herein makes use of a commercial hair brush as a template to create concave micro-well impressions in agarose. This technique is easy, inexpensive, and adaptable and also has the ability to produce uniform, homogenous cancer spheroids, with large diameter (∼1000 μm) and thickness (∼250 μm), within 24 to 48 hr after cell seeding. The 3D spheroids produced using the agarose micro-well platform function as an excellent 3D in vitro model for understanding the extent of penetration, uptake, and distribution of targeted cargos such as a diagnostic or therapeutic agents for identification and treatment of cancer. © 2021 Wiley Periodicals LLC. Basic Protocol 1: Fabrication of agarose micro-well scaffold for growing tumor spheroids using a commercial hair brush Basic Protocol 2: Formation of homogenous tumor spheroids in agarose micro-well platform Basic Protocol 3: Assessing viability of 3D tumor spheroids grown in agarose micro-wells using confocal microscopy Basic Protocol 4: Analyzing uptake and penetration of targeted fluorescent bioconjugate in 3D tumor spheroids using two-photon imaging.

Keywords:  agarose hydrogel; comb template; micro-well platform; tumor spheroids

DOI:  https://doi.org/10.1002/cpz1.199
Cancer Sci. 2021 Jul 19.

Reactive oxygen species in cancer: current findings and future directions.

Hajime Nakamura, Kohichi Takada.

  Reactive oxygen species (ROS), a class of highly bioactive molecules, have been widely studied in various types of cancers. ROS are considered to be normal byproducts of numerous cellular processes. Typically, cancer cells exhibit higher basal levels of ROS compared to normal cells as a result of an imbalance between oxidants and antioxidants. ROS have a dual role in cell metabolism: At low to moderate levels, ROS act as signal transducers to activate cell proliferation, migration, invasion and angiogenesis. In contrast, high levels of ROS cause damage to proteins, nucleic acids, lipids, membranes, and organelles, leading to cell death. Extensive studies have revealed that anticancer therapies that manipulate ROS levels, including immunotherapies, show promising in vitro as well as in vivo results. In this review, we summarize molecular mechanisms and oncogenic functions that modulate ROS levels and are useful for the development of cancer therapeutic strategies. This review also provides insights into the future development of effective agents that regulate the redox system for cancer treatment.

Keywords:  Cell Death; Neoplasms; Oxidative Stress; Reactive Oxygen Species; Therapeutics

DOI:  https://doi.org/10.1111/cas.15068
Adv Biol (Weinh). 2021 Jul 23. e2101017

High-Yield Production, Characterization, and Functionalization of Recombinant Magnetosomes in the Synthetic Bacterium Rhodospirillum rubrum "magneticum".

Frank Mickoleit, Sabine Rosenfeldt, Mauricio Toro-Nahuelpan, Miroslava Schaffer, Anna S Schenk, Jürgen M Plitzko, Dirk Schüler.

  Recently, the photosynthetic Rhodospirillum rubrum has been endowed with the ability of magnetosome biosynthesis by transfer and expression of biosynthetic gene clusters from the magnetotactic bacterium Magnetospirillum gryphiswaldense. However, the growth conditions for efficient magnetite biomineralization in the synthetic R. rubrum "magneticum", as well as the particles themselves (i.e., structure and composition), have so far not been fully characterized. In this study, different cultivation strategies, particularly the influence of temperature and light intensity, are systematically investigated to achieve optimal magnetosome biosynthesis. Reduced temperatures ≤16 °C and gradual increase in light intensities favor magnetite biomineralization at high rates, suggesting that magnetosome formation might utilize cellular processes, cofactors, and/or pathways that are linked to photosynthetic growth. Magnetosome yields of up to 13.6 mg magnetite per liter cell culture are obtained upon photoheterotrophic large-scale cultivation. Furthermore, it is shown that even more complex, i.e., oligomeric, catalytically active functional moieties like enzyme proteins can be efficiently expressed on the magnetosome surface, thereby enabling the in vivo functionalization by genetic engineering. In summary, it is demonstrated that the synthetic R. rubrum "magneticum" is a suitable host for high-yield magnetosome biosynthesis and the sustainable production of genetically engineered, bioconjugated magnetosomes.

Keywords:  Rhodospirillum rubrum; genetic engineering; magnetic nanoparticles; magnetosomes; phototrophic cultivation

DOI:  https://doi.org/10.1002/adbi.202101017
BMC Microbiol. 2021 Jul 19. 21(1): 218

Colorectal cancer treatment using bacteria: focus on molecular mechanisms.

Sara Ebrahimzadeh, Hossein Ahangari, Alireza Soleimanian, Kamran Hosseini, Vida Ebrahimi, Tohid Ghasemnejad, Saiedeh Razi Soofiyani, Vahideh Tarhriz, Shirin Eyvazi.

   BACKGROUND: Colorectal cancer which is related to genetic and environmental risk factors, is among the most prevalent life-threatening cancers. Although several pathogenic bacteria are associated with colorectal cancer etiology, some others are considered as highly selective therapeutic agents in colorectal cancer. Nowadays, researchers are concentrating on bacteriotherapy as a novel effective therapeutic method with fewer or no side effects to pay the way of cancer therapy. The introduction of advanced and successful strategies in bacterial colorectal cancer therapy could be useful to identify new promising treatment strategies for colorectal cancer patients.
MAIN TEXT: In this article, we scrutinized the beneficial effects of bacterial therapy in colorectal cancer amelioration focusing on different strategies to use a complete bacterial cell or bacterial-related biotherapeutics including toxins, bacteriocins, and other bacterial peptides and proteins. In addition, the utilization of bacteria as carriers for gene delivery or other known active ingredients in colorectal cancer therapy are reviewed and ultimately, the molecular mechanisms targeted by the bacterial treatment in the colorectal cancer tumors are detailed.
CONCLUSIONS: Application of the bacterial instrument in cancer treatment is on its way through becoming a promising method of colorectal cancer targeted therapy with numerous successful studies and may someday be a practical strategy for cancer treatment, particularly colorectal cancer.

Keywords:  Bacterial peptides; Bacteriocins; Biotherapeutical toxins; Colorectal cancer

DOI:  https://doi.org/10.1186/s12866-021-02274-3
ACS Appl Mater Interfaces. 2021 Jul 22.

Hypoxia-Overcoming Breast-Conserving Treatment by Magnetothermodynamic Implant for a Localized Free-Radical Burst Combined with Hyperthermia.

Jingsong Lu, Zhenhu Guo, Wensheng Xie, Yongjie Chi, Wanling Xu, Xiaoxiao Guo, Xiaohan Gao, Jielin Ye, Benhua Xu, Rong Zheng, Xiaodan Sun, Xiumei Wang, Shenglei Che, Jing Yu, Lingyun Zhao.

  For the purpose of improving the quality of life and minimizing the psychological morbidity of a mastectomy, breast-conserving treatment (BCT) has become the more preferable choice in breast cancer patients. Meanwhile, tumor hypoxia has been increasingly recognized as a major deleterious factor in cancer therapies. In the current study, a novel, effective, and noninvasive magnetothermodynamic strategy based on an oxygen-independent free-radical burst for hypoxia-overcoming BCT is proposed. Radical precursor (AIPH) and iron oxide nanoparticles (IONPs) are coincorporated within the alginate (ALG) hydrogel, which is formed in situ within the tumor tissue by leveraging the cross-linking effect induced by the local physiological Ca2+ with ALG solution. Inductive heating is mediated by IONPs under AMF exposure, and consequently, regardless of the tumor hypoxia condition, a local free-radical burst is achieved by thermal decomposition of AIPH via AMF responsivity. The combination of magnetic hyperthermia and oxygen-irrelevant free-radical production effectively enhances the in vitro cytotoxic effect and also remarkably inhibits tumor proliferation. This study provides a valuable protocol for an hypoxia-overcoming strategy and also an alternative formulation candidate for noninvasive BCT.

Keywords:  alkyl free radical; breast-conserving treatment; hydrogel; hypoxia-irrelevant; thermal response

DOI:  https://doi.org/10.1021/acsami.1c09355