bims-mricoa 2021-09-19 papers

bims-mricoa

Biomed News

on MRI contrast agents

Issue of 2021–09–19
nine papers selected by
Merve Yavuz, Bilkent University

Smart magnetic resonance imaging-based theranostics for cancer.
Minicells from Highly Genome Reduced Escherichia coli: Cytoplasmic and Surface Expression of Recombinant Proteins and Incorporation in the Minicells.
A comprehensive assessment of the biocompatibility of Magnetospirillum gryphiswaldense MSR-1 bacterial magnetosomes in vitro and in vivo.
Superparamagnetic Iron Oxide Nanoparticles: Cytotoxicity, Metabolism, and Cellular Behavior in Biomedicine Applications.
Magnetic systems for cancer immunotherapy.
Intelligent Design of Ultrasmall Iron Oxide Nanoparticle-Based Theranostics.
Bacterial-based cancer therapy: An emerging toolbox for targeted drug/gene delivery.
Therapeutic Modification of Hypoxia.
Influencing factors and strategies of enhancing nanoparticles into tumors in vivo.

Theranostics. 2021 ;11(18): 8706-8737

Smart magnetic resonance imaging-based theranostics for cancer.

Beatriz Brito, Thomas W Price, Juan Gallo, Manuel Bañobre-López, Graeme J Stasiuk.

  Smart theranostics are dynamic platforms that integrate multiple functions, including at least imaging, therapy, and responsiveness, in a single agent. This review showcases a variety of responsive theranostic agents developed specifically for magnetic resonance imaging (MRI), due to the privileged position this non-invasive, non-ionising imaging modality continues to hold within the clinical imaging field. Different MRI smart theranostic designs have been devised in the search for more efficient cancer therapy, and improved diagnostic efficiency, through the increase of the local concentration of therapeutic effectors and MRI signal intensity in pathological tissues. This review explores novel small-molecule and nanosized MRI theranostic agents for cancer that exhibit responsiveness to endogenous (change in pH, redox environment, or enzymes) or exogenous (temperature, ultrasound, or light) stimuli. The challenges and obstacles in the design and in vivo application of responsive theranostics are also discussed to guide future research in this interdisciplinary field towards more controllable, efficient, and diagnostically relevant smart theranostics agents.

Keywords:  cancer; contrast agents; magnetic resonance imaging; nanoparticles; responsive; small molecules; smart; theranostics; therapy

DOI:  https://doi.org/10.7150/thno.57004
ACS Synth Biol. 2021 Sep 13.

Minicells from Highly Genome Reduced Escherichia coli: Cytoplasmic and Surface Expression of Recombinant Proteins and Incorporation in the Minicells.

Hanna Yu, Andrei V Khokhlatchev, Claude Chew, Anuradha Illendula, Mark Conaway, Kelly Dryden, Denicar Lina Nascimento Fabris Maeda, Vignesh Rajasekaran, Mark Kester, Steven L Zeichner.

  Minicells, small cells lacking a chromosome, produced by bacteria with mutated min genes, which control cell division septum placement, have many potential uses. Minicells have contributed to basic bacterial physiology studies and can enable new biotechnological applications, including drug delivery and vaccines. Genome-reduced bacteria are another informative area of investigation. Investigators identified that with even almost 30% of the E. coli genome deleted, the bacteria still live. In biotechnology and synthetic biology, genome-reduced bacteria offer certain advantages. With genome-reduced bacteria, more recombinant genes can be placed into genome-reduced chromosomes and fewer cell resources are devoted to purposes apart from biotechnological goals. Here, we show that these two technologies can be combined: min mutants can be made in genome-reduced E. coli. The minC minD mutant genome-reduced E. coli produce minicells that concentrate engineered recombinant proteins within these spherical delivery systems. We expressed recombinant GFP protein in the cytoplasm of genome-reduced bacteria and showed that it is concentrated within the minicells. We also expressed proteins on the surfaces of minicells made from genome-reduced bacteria using a recombinant Gram-negative AIDA-I autotransporter expression cassette. Some autotransporters, like AIDA-I, are concentrated at the bacterial poles, where minicells bud. Recombinant proteins expressed on surfaces of the genome-reduced bacteria are concentrated on the minicells. Minicells made from genome-reduced bacteria may enable useful biotechnological innovations, such as drug delivery vehicles and vaccine immunogens.

Keywords:  antigens; autotransporter; cell engineering; genome reduced bacteria; minicell; recombinant protein expression; vaccines

DOI:  https://doi.org/10.1021/acssynbio.1c00375
Toxicology. 2021 Sep 14. pii: S0300-483X(21)00272-9. [Epub ahead of print] 152949

A comprehensive assessment of the biocompatibility of Magnetospirillum gryphiswaldense MSR-1 bacterial magnetosomes in vitro and in vivo.

Xiaohui Nan, Yan Teng, Jiesheng Tian, Zhiyuan Hu, Qiaojun Fang.

  Bacterial magnetosomes (BMs) are iron oxide nanoparticles synthesized naturally by magnetotactic bacteria, made up of nano-sized inorganic crystals enclosed by a lipid bilayer membrane. Due to several superior characteristics, such as the narrow size distribution, uniform morphology, high purity and crystallinity, single magnetic domain as well as easy surface modification, increasing biomedical and biotechnological applications of BMs have been developed. The attracted wide attentions raise the urge for the evaluation of safety and toxicity. In this work, we performed a rather comprehensive and systematic assessment of in vitro and in vivo toxicity of BMs from MSR-1, including the cytotoxicity, mice bodyweights, blood test, organ coefficients, inflammation, and hemocompatibility study. We found that BMs have good biocompatibility except for influences on the immune response as demonstrated by enhanced activation of the complement system and inhibition of lymphocyte proliferation when used with an excessive concentration. BMs induced the production of reactive oxygen species (ROS) in macrophages at a dose-dependent manner but did not cause cell membrane damage and cell cycle arrest until the concentration is approximately 40 times the clinical dosage. We anticipate our work will guide modifications of BMs and expand their future applications.

Keywords:  Bacterial magnetosomes (BMs); Biocompatibility; Cytotoxicity; Hemocompatibility; Inflammation; Reactive oxygen species (ROS)

DOI:  https://doi.org/10.1016/j.tox.2021.152949
Int J Nanomedicine. 2021 ;16 6097-6113

Superparamagnetic Iron Oxide Nanoparticles: Cytotoxicity, Metabolism, and Cellular Behavior in Biomedicine Applications.

Hao Wei, Yangnan Hu, Junguo Wang, Xia Gao, Xiaoyun Qian, Mingliang Tang.

  Superparamagnetic iron oxide nanoparticles (SPIONs) have been widely investigated and applied in the field of biomedicine due to their excellent superparamagnetic properties and reliable traceability. However, with the optimization of core composition, shell types and transfection agents, the cytotoxicity and metabolism of different SPIONs have great differences, and the labeled cells also show different cellular behaviors. Therefore, a holistic review of the construction and application of SPIONs is desired. This review focuses the advances of SPIONs in the field of biomedicine in recent years. After summarizing the toxicity of different SPIONs, the uptake, distribution and metabolism of SPIONs in vitro were discussed. Then, the regulation of labeled-cells behavior is outlined. Furthermore, the major challenges in the optimization process of SPIONs and insights on its future developments are proposed.

Keywords:  biological behavior; cytotoxicity; stem cells; superparamagnetic iron oxide nanoparticles

DOI:  https://doi.org/10.2147/IJN.S321984
Acta Pharm Sin B. 2021 Aug;11(8): 2172-2196

Magnetic systems for cancer immunotherapy.

Nicole B Day, William C Wixson, C Wyatt Shields.

  Immunotherapy is a rapidly developing area of cancer treatment due to its higher specificity and potential for greater efficacy than traditional therapies. Immune cell modulation through the administration of drugs, proteins, and cells can enhance antitumoral responses through pathways that may be otherwise inhibited in the presence of immunosuppressive tumors. Magnetic systems offer several advantages for improving the performance of immunotherapies, including increased spatiotemporal control over transport, release, and dosing of immunomodulatory drugs within the body, resulting in reduced off-target effects and improved efficacy. Compared to alternative methods for stimulating drug release such as light and pH, magnetic systems enable several distinct methods for programming immune responses. First, we discuss how magnetic hyperthermia can stimulate immune cells and trigger thermoresponsive drug release. Second, we summarize how magnetically targeted delivery of drug carriers can increase the accumulation of drugs in target sites. Third, we review how biomaterials can undergo magnetically driven structural changes to enable remote release of encapsulated drugs. Fourth, we describe the use of magnetic particles for targeted interactions with cellular receptors for promoting antitumor activity. Finally, we discuss translational considerations of these systems, such as toxicity, clinical compatibility, and future opportunities for improving cancer treatment.

Keywords:  BW, body weight; Biomaterials; CpG, cytosine-phosphate-guanine; DAMP, damage associated molecular pattern; Drug delivery; EPR, enhanced permeability and retention; FFR, field free region; HS-TEX, heat-stressed tumor cell exosomes; HSP, heat shock protein; ICD, immunogenic cell death; IVIS, in vivo imaging system; Immunotherapy; MICA, MHC class I-related chain A; MPI, magnetic particle imaging; Magnetic hyperthermia; Magnetic nanoparticles; Microrobotics; ODNs, oligodeoxynucleotides; PARP, poly(adenosine diphosphate-ribose) polymerase; PDMS, polydimethylsiloxane; PEG, polyethylene glycol; PLGA, poly(lactic-co-glycolic acid); PNIPAM, poly(N-isopropylacrylamide); PVA, poly(vinyl alcohol); SDF, stromal cell derived-factor; SID, small implantable device; SLP, specific loss power

DOI:  https://doi.org/10.1016/j.apsb.2021.03.023
ACS Appl Mater Interfaces. 2021 Sep 17.

Intelligent Design of Ultrasmall Iron Oxide Nanoparticle-Based Theranostics.

Yue Gao, Xiangyang Shi, Mingwu Shen.

  Rapid advances in nanotechnology have opened up innovative trails to break through the current limitation in clinical treatments of cancer and other critical diseases that plague human beings. Ultrasmall iron oxide nanoparticles (USIO NPs) with sizes smaller than 5 nm have been emerging as a novel category of nanomaterials with increasing interest in the biomedical domains. To overcome their intrinsic shortcomings, naked USIO NPs can be functionalized, clustered, assembled, or incorporated with other nanomaterials to generate various kinds of intelligent nanoplatforms for single-mode or dynamic magnetic resonance (MR) imaging, multimode imaging, as well as imaging-guided precision therapy. In this spotlight on applications, first, we propose the principal aspects in the design and application of USIO NPs for biomedical uses. Second, we cover the recent design strategies of USIO NP-based nanoplatforms mainly developed by our group, describe the rationale on the combination of other functional materials with USIO NPs, and review their resultant applications in theranostics. In addition, we provide herein a perspective on the possible future directions toward USIO NP-based nanoplatforms as smart nanomedicines.

Keywords:  MR imaging; nanoclusters; nanohybrids; theranostics; ultrasmall iron oxide nanoparticles

DOI:  https://doi.org/10.1021/acsami.1c13341
Biomaterials. 2021 Sep 10. pii: S0142-9612(21)00481-6. [Epub ahead of print]277 121124

Bacterial-based cancer therapy: An emerging toolbox for targeted drug/gene delivery.

Dewu Lin, Xiaolan Feng, Bingjie Mai, Xin Li, Fei Wang, Jiexi Liu, Xin Liu, Kun Zhang, Xiaobing Wang.

  Precise targeting and high therapeutic efficiency are the major requisites of personalized cancer treatment. However, some unique features of the tumor microenvironment (TME) such as hypoxia, low pH and elevated interstitial fluid pressure cause cancer cells resistant to most therapies. Bacteria are increasingly being considered for targeted tumor therapy owing to their intrinsic tumor tropism, high motility as well as the ability to rapidly colonize in the favorable TME. Compared to other nano-strategies using peptides, aptamers, and other biomolecules, tumor-targeting bacteria are largely unaffected by the tumor cells and microenvironment. On the contrary, the hypoxic TME is highly conducive to the growth of facultative anaerobes and obligate anaerobes. Live bacteria can be further integrated with anti-cancer drugs and nanomaterials to increase the latter's targeted delivery and accumulation in the tumors. Furthermore, anaerobic and facultatively anaerobic bacteria have also been combined with other anti-cancer therapies to enhance therapeutic effects. In this review, we have summarized the applications and advantages of using bacteria for targeted tumor therapy (Scheme 1) in order to aid in the design of novel intelligent drug delivery systems. The current challenges and future prospects of tumor-targeting bacterial nanocarriers have also been discussed.

Keywords:  Bacterial carrier; Biomaterials; Cancer theranostics; Genetic engineering; Targeting delivery

DOI:  https://doi.org/10.1016/j.biomaterials.2021.121124
Clin Oncol (R Coll Radiol). 2021 Sep 14. pii: S0936-6555(21)00332-0. [Epub ahead of print]

Therapeutic Modification of Hypoxia.

M R Horsman, B S Sørensen, M Busk, D W Siemann.

  Regions of reduced oxygenation (hypoxia) are a characteristic feature of virtually all animal and human solid tumours. Numerous preclinical studies, both in vitro and in vivo, have shown that decreasing oxygen concentration induces resistance to radiation. Importantly, hypoxia in human tumours is a negative indicator of radiotherapy outcome. Hypoxia also contributes to resistance to other cancer therapeutics, including immunotherapy, and increases malignant progression as well as cancer cell dissemination. Consequently, substantial effort has been made to detect hypoxia in human tumours and identify realistic approaches to overcome hypoxia and improve cancer therapy outcomes. Hypoxia-targeting strategies include improving oxygen availability, sensitising hypoxic cells to radiation, preferentially killing these cells, locating the hypoxic regions in tumours and increasing the radiation dose to those areas, or applying high energy transfer radiation, which is less affected by hypoxia. Despite numerous clinical studies with each of these hypoxia-modifying approaches, many of which improved both local tumour control and overall survival, hypoxic modification has not been established in routine clinical practice. Here we review the background and significance of hypoxia, how it can be imaged clinically and focus on the various hypoxia-modifying techniques that have undergone, or are currently in, clinical evaluation.

Keywords:  Hypoxia; hypoxia imaging; radiotherapy; therapeutic modifiers

DOI:  https://doi.org/10.1016/j.clon.2021.08.014
Acta Pharm Sin B. 2021 Aug;11(8): 2265-2285

Influencing factors and strategies of enhancing nanoparticles into tumors in vivo.

Mingming Zhang, Shan Gao, Dongjuan Yang, Yan Fang, Xiaojie Lin, Xuechao Jin, Yuli Liu, Xiu Liu, Kexin Su, Kai Shi.

  The administration of nanoparticles (NPs) first faces the challenges of evading renal filtration and clearance of reticuloendothelial system (RES). After that, NPs infiltrate through the expanded endothelial space and penetrated the dense stroma of tumor microenvironment to tumor cells. As long as possible to prolong the time of NPs remaining in tumor tissue, NPs release active agent and induce pharmacological action. This review provides a comprehensive summary of the physical and chemical properties of NPs and the influence of various biological factors in tumor microenvironment, and discusses how to improve the final efficacy through adjusting the characteristics and structure of NPs. Perspectives and future directions are also provided.

Keywords:  Cancer-associated fibroblasts; Drug delivery; Extracellular matrix; Nanoparticles; Reticuloendothelial system; Tumor microenvironment; Tumor stroma; Tumor vascular endothelial cells

DOI:  https://doi.org/10.1016/j.apsb.2021.03.033