Magnetic nanoparticles have been at the center of biomedical research for decades, primarily for their applications in magnetic resonance imaging (MRI) and magnetic particle imaging (MPI). Superparamagnetic particles, typically based on iron oxide crystals, are effective in both modalities, although each requires distinct magnetic properties for optimal performance. We investigated the performance of nanoparticles based on a nickel-substituted ferrite core and compared them to standard maghemite iron oxide nanoparticles. We synthesized γ-Fe2O3 and Ni x Fe2-x O3 nanoparticles and coated them with a statistical copolymer poly-(N,N-dimethylacrylamide-co-acrylic acid). In vitro testing included X-ray diffraction (XRD), Mössbauer spectroscopy, magnetometry, magnetic resonance relaxometry, magnetic particle spectroscopy, and imaging. In vivo testing involved monitoring of nanoparticle biodistribution using MPI and MRI after intracardial application in a murine model. Mössbauer spectra suggest that the Ni-substituted nanoparticles consist of a stoichiometric NiFe2O4 ferrite and a poorly crystalline antiferromagnetic iron-(III) oxide-hydroxide phase. Amorphous-like impurities in Ni x Fe2-x O3 nanoparticles were probably responsible for lower saturation magnetization than that of γ-Fe2O3 nanoparticles, as was proved by magnetometry, which led to lower r 2 relaxivity. However, MPI revealed a higher signal in the spectrum and superior imaging performance of Ni x Fe2-x O3 compared to γ-Fe2O3 particles, likely due to shorter Néél and Brownian relaxation times. Both types of nanoparticles showed similar performance in bimodal MRI/MPI imaging in vivo. They were detected in the liver immediately after application and appeared in the spleen within 24 h. Long-term localization in the lymph nodes was also observed. Substituting an iron with a nickel ion in the core altered the magnetic properties, leading to lower saturation magnetization and an increased signal in the magnetic particle spectra, which enhanced their performance in MPI. This study demonstrates that γ-Fe2O3 and Ni x Fe2-x O3 nanoparticles are both suitable for combined MRI/MPI imaging; magnetic particle imaging provides a highly specific signal for anatomical magnetic resonance images.
- Klíčová slova
- magnetic particle imaging, magnetic resonance imaging, nickel ferrite nanoparticles, r2 relaxivity, saturation magnetization,
- Publikační typ
- časopisecké články MeSH
To address the challenge of drug accumulation and penetration at the tumor site(s), herein we describe a first-in-class nanocarrier containing 24 copies each of two bioactive peptides (BAPs) genetically fused in frame to the 24 N-termini of a human ferritin H-type construct, named THE-10. The two BAPs are specific for PD-L1 and integrin αVβ3/αVβ5 plus Neuropilin (iRGD) respectively, conferring immune checkpoint blockade and drug-internalization properties. In turn, the THE-10 backbone brings 48 BAPs contiguous for synergism, prolonged blood half-life, and release into the tumor microenvironment upon conditional cleavage of a metalloprotease-sensitive site. Predicted THE-10 multitasking activity was experimentally supported as follows. Size-exclusion chromatography and surface plasmon resonance demonstrated BAP cleavage/release and receptor binding (nanomolar KD). Live-cell/time-lapse imaging demonstrated 4-fold-increased internalization of naked therapeutic antibodies, mirrored by enhanced cytotoxicity of the corresponding Antibody-Drug Conjugate. Slight antitumor effects were observed in vivo by treating immune checkpoint-sensitive syngeneic mouse colorectal model with THE-10 alone. Drug boosting was instead considerable on colorectal and pancreatic tumor allografts when THE-10 was co-administered with both small and large chemotherapeutic agents, outperforming the original iRGD cyclic peptide. Thus, THE-10 may enhance target therapy, chemotherapy and immunotherapy altogether, e.g. it candidates as a multitasking, all-round, antineoplastic therapy booster.
- Klíčová slova
- Human ferritin nanocarrier, Peptide grafting, cancer therapy booster,
- MeSH
- ferritiny * chemie genetika farmakologie MeSH
- imunoterapie * MeSH
- lidé MeSH
- myši MeSH
- nádorové buněčné linie MeSH
- nanočástice * chemie MeSH
- nosiče léků * chemie MeSH
- protinádorové látky farmakologie chemie MeSH
- rekombinantní proteiny chemie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- ferritiny * MeSH
- nosiče léků * MeSH
- protinádorové látky MeSH
- rekombinantní proteiny MeSH
Dictyosphaerium chlorelloides is a green microalga from the Chlorella clade that produces highly viscous exocellular polysaccharides. The cell wall polysaccharides of this alga have not been studied in detail. In this article, water-soluble polysaccharides from D. chlorelloides biomass were extracted with hot water and purified by preparative chromatography. The composition, structural features and molecular masses of subsequently eluted fractions F1, F2, F3, F4 and F5 (minor) were determined. Three high-yield products F1, F3 and F4 consisted mainly of galactopyranosyl, 2-O-methyl-galactopyranosyl, rhamnopyranosyl and mannopyranosyl units at different proportions, while F2 was rich in glucose. Immunoactivity of these fractions was evidenced in a mixed population of immune cells derived from mice spleens after incubation with polysaccharides by flow cytometry, MTT and Immunospot assays. These fractions, except F2, demonstrated selective immunostimulant activity, and the F1 fraction induced the most potent effect, closely followed by the F3 and F4 fractions. The in vivo mechanism of their action is associated with the activation of innate immunity and shapes the immune response to the Th1 type.
- Klíčová slova
- Dictyosphaerium chlorelloides, Immunomodulating activity, Microalgae biomass, Structure, Water-soluble polysaccharides,
- MeSH
- adjuvancia imunologická * farmakologie chemie izolace a purifikace MeSH
- buněčná stěna * chemie MeSH
- Chlorophyta * chemie MeSH
- mikrořasy * chemie MeSH
- myši MeSH
- polysacharidy * chemie farmakologie izolace a purifikace imunologie MeSH
- slezina cytologie imunologie účinky léků MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- adjuvancia imunologická * MeSH
- polysacharidy * MeSH
Nanoparticles are commonly used in diagnostics and therapy. They are also increasingly being implemented in cancer immunotherapy because of their ability to deliver drugs and modulate the immune system. However, the effect of nanoparticles on immune cells involved in the anti-tumor immune response is not well understood. The study reported here showed that nickel-doped maghemite nanoparticles (FN NP) are differentially cytotoxic to cultured mouse and human cancer cell lines, causing their death without negatively impacting the subsequent anticancer immune response. It also found that FN NP induced cell death in the mouse colorectal cancer cell line CT26 and human prostate cancer cell line PC-3, but not in the human prostate cancer cell line LNCaP. The induced cancer cell death did not affect the phenotype and responsivity of the isolated mouse peritoneal macrophages, or ex vivo-generated mouse bone marrow-derived, or human monocyte-derived dendritic cells. Additionally, the induced cancer cell death did not prevent the ex vivo-generated mouse or human dendritic cells from stimulating lymphocytes and enriching cell cultures with cancer cell-reactive T-cells. In conclusion, this study shows that FN NP could be a valuable platform for targeting cancer cells without causing immunosuppressive effects on the subsequent anticancer immune response.
- Klíčová slova
- Nanoparticles, T-cells, cancer cells, dendritic cells, immunogenic cell death, macrophages,
- MeSH
- buňky PC-3 MeSH
- dendritické buňky * imunologie MeSH
- imunoterapie * metody MeSH
- lidé MeSH
- myši MeSH
- nádorové buněčné linie MeSH
- nádory prostaty imunologie terapie MeSH
- nádory imunologie terapie MeSH
- nikl * chemie imunologie MeSH
- železité sloučeniny chemie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- ferric oxide MeSH Prohlížeč
- nikl * MeSH
- železité sloučeniny MeSH
Soft tissue sarcomas are aggressive mesenchymal-origin malignancies. Undifferentiated pleomorphic sarcoma (UPS) belongs to the aggressive, high-grade, and least characterized sarcoma subtype, affecting multiple tissues and metastasizing to many organs. The treatment of localized UPS includes surgery in combination with radiation therapy. Metastatic forms are treated with chemotherapy. Immunotherapy is a promising treatment modality for many cancers. However, the development of immunotherapy for UPS is limited due to its heterogeneity, antigenic landscape variation, lower infiltration with immune cells, and a limited number of established patient-derived UPS cell lines for preclinical research. In this study, we established and characterized a novel patient-derived UPS cell line, JBT19. The JBT19 cells express PD-L1 and collagen, a ligand of the immune checkpoint molecule LAIR-1. JBT19 cells can form spheroids in vitro and solid tumors in immunodeficient nude mice. We found JBT19 cells induce expansion of JBT19-reactive autologous and allogeneic NK, T, and NKT-like cells, and the reactivity of the expanded cells was associated with cytotoxic impact on JBT19 cells. The PD-1 and LAIR-1 ligand-expressing JBT19 cells show ex vivo immunogenicity and effective in vivo xenoengraftment properties that can offer a unique resource in the preclinical research developing novel immunotherapeutic interventions in the treatment of UPS.
- MeSH
- antigeny CD274 metabolismus MeSH
- buněčné linie MeSH
- imunoterapie MeSH
- lidé MeSH
- ligandy MeSH
- maligní fibrózní histiocytom * MeSH
- myši nahé MeSH
- myši MeSH
- sarkom * patologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- antigeny CD274 MeSH
- ligandy MeSH
For centuries human civilization has cultivated oats, and now they are consumed in various forms of food, from instant breakfasts to beverages. They are a nutrient-rich food containing linear mixed-linkage (1 → 3) (1 → 4)-β-d-glucans, which are relatively well soluble in water and responsible for various biological effects: the regulation of the blood cholesterol level, as well as being anti-inflammatory, prebiotic, antioxidant, and tumor-preventing. Numerous studies, especially in the last two decades, highlight the differences in the biological properties of the oat β-d-glucan fractions of low, medium, and high molecular weight. These fractions differ in their features due to variations in bioavailability related to the rheological properties of these polysaccharides, and their association with food matrices, purity, and mode of preparation or modification. There is strong evidence that, under different conditions, the molecular weight may determine the potency of oat-extracted β-d-glucans. In this review, we intend to give a concise overview of the properties and studies of the biological activities of oat β-d-glucan preparations depending on their molecular weight and how they represent a prospective ingredient of functional food with the potential to prevent or modulate various pathological conditions.
- Klíčová slova
- cancer, cereal β-d-glucans, glycaemia, immunity, microbiome, molecular weight, oats,
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Cancer, bacteria, and immunity relationships are much-debated topics in the last decade. Microbiome's importance for metabolic and immunologic modulation of the organism adaptation and responses has become progressively evident, and models to study these relationships, especially about carcinogenesis, have acquired primary importance. The availability of germ-free (GF) animals, i.e., animals born and maintained under completely sterile conditions avoiding the microbiome development offers a unique tool to investigate the role that bacteria can have in carcinogenesis and tumor development. The comparison between GF animals with the conventional (CV) counterpart with microbiome can help to evidence conditions and mechanisms directly involving bacterial activities in the modulation of carcinogenesis processes. Here, we review the literature about spontaneous cancer and cancer modeling in GF animals since the early studies, trying to offer a practical overview on the argument.
- Klíčová slova
- colorectal cancer, germ-free animals, induced tumors, microbiome, spontaneous tumors,
- MeSH
- Bacteria MeSH
- gnotobiologické modely * MeSH
- karcinogeneze MeSH
- mikrobiota * MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Hot water extract from biomass of heterotrophic mutant green alga Parachlorella kessleri HY1 (Chlorellaceae) was deproteinised, and three polysaccharidic fractions were obtained by preparative chromatography. The low-molecular fraction (1.5 × 104g mol-1) was defined mainly as branched O-2-β-xylo-(1→3)-β-galactofuranan where xylose is partially methylated at O-4. Two high-molecular fractions (3.05 × 105 and 9.84 × 104g mol-1) were complex polysaccharides containing α-l-rhamnan and xylogalactofuranan parts in different ratios. The polysaccharides were well soluble in hot water and, upon cooling, tended to self-segregate. Immunomodulatory activities of the obtained fractions were preliminary tested using ELISA, FACS and ImmunoSpot kits. The polysaccharides increased the TNF-α production in melanoma bearing mice with much higher intensity than in healthy mice. This was in agreement with the FACS results on T and B cells indicating their possibly secondary activation by innate immunity cells.
- Klíčová slova
- Aggregation, Chlorella, Immunomodulatory activity, Rhamnans, Structure, Xylogalactofuranan,
- MeSH
- B-lymfocyty účinky léků imunologie patologie MeSH
- CD antigeny genetika imunologie MeSH
- Chlorophyta chemie MeSH
- imunologické faktory chemie izolace a purifikace farmakologie MeSH
- interferon gama genetika imunologie MeSH
- interleukin-2 genetika imunologie MeSH
- interleukin-4 genetika imunologie MeSH
- lipopolysacharidy antagonisté a inhibitory farmakologie MeSH
- melanom imunologie patologie MeSH
- metylace MeSH
- molekulová hmotnost MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- nádory kůže imunologie patologie MeSH
- polysacharidy chemie izolace a purifikace farmakologie MeSH
- primární buněčná kultura MeSH
- regulace genové exprese účinky léků MeSH
- rostlinné extrakty chemie MeSH
- rozpustnost MeSH
- sacharidové sekvence MeSH
- T-lymfocyty účinky léků imunologie patologie MeSH
- TNF-alfa genetika imunologie MeSH
- voda MeSH
- xylosa chemie izolace a purifikace MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- CD antigeny MeSH
- Il4 protein, mouse MeSH Prohlížeč
- imunologické faktory MeSH
- interferon gama MeSH
- interleukin-2 MeSH
- interleukin-4 MeSH
- lipopolysacharidy MeSH
- polysacharidy MeSH
- rostlinné extrakty MeSH
- TNF-alfa MeSH
- voda MeSH
- xylosa MeSH
New foods and natural biological modulators have recently become of scientific interest in the investigation of the value of traditional medical therapeutics. Glucans have an important part in this renewed interest. These fungal wall components are claimed to be useful for various medical purposes and they are obtained from medicinal mushrooms commonly used in traditional Oriental medicine. The immunotherapeutic properties of fungi extracts have been reported, including the enhancement of anticancer immunity responses. These properties are principally related to the stimulation of cells of the innate immune system. The discovery of specific receptors for glucans on dendritic cells (dectin-1), as well as interactions with other receptors, mainly expressed by innate immune cells (e.g., Toll-like receptors, complement receptor-3), have raised new attention toward these products as suitable therapeutic agents. We briefly review the characteristics of the glucans from mycelial walls as modulators of the immunity and their possible use as antitumor treatments.
- MeSH
- adjuvancia imunologická chemie terapeutické užití MeSH
- Agaricales chemie MeSH
- beta-glukany chemie terapeutické užití MeSH
- buněčné extrakty terapeutické užití MeSH
- dendritické buňky účinky léků MeSH
- lektiny typu C metabolismus MeSH
- lidé MeSH
- makrofágy účinky léků imunologie MeSH
- myši MeSH
- přirozená imunita účinky léků MeSH
- protinádorové látky chemie imunologie terapeutické užití MeSH
- signální transdukce imunologie MeSH
- tradiční orientální medicína MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Názvy látek
- adjuvancia imunologická MeSH
- beta-glukany MeSH
- buněčné extrakty MeSH
- dectin 1 MeSH Prohlížeč
- lektiny typu C MeSH
- protinádorové látky MeSH