The Interaction of Biomedical Nanoparticles with the Immune System

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cellular Immunology".

Deadline for manuscript submissions: closed (31 August 2021) | Viewed by 32138

Special Issue Editors


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Guest Editor
Department of Biotechnology and Biosciences, University of Milano-Bicocca, Piazza della Scienza, 220126 Milano, Italy
Interests: inflammation; innate immunity; host pathogen interaction; Pattern Recognition Receptors; T cells; T cell tolerance; autoimmunity

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Guest Editor
Institute of Agricultural and Environmental Research and Technology (IITAA), University of the Azores, Angra do Heroísmo, Portugal
Interests: biological chemistry; antioxidants; anti-inflammatories; bioactive compounds; polyphenols
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Special Issue Information

Dear Colleagues,

Nanomedicine has been opening a new avenue of research in cancer therapy, drug delivery, and immune regulation. Nevertheless, the use of nanoparticles is a double-edge sword. While the benefits of nanotechnology to human civilization are seemingly immeasurable, these particles can also lead to harmful effects to human health. In vivo studies have been showing that when nanoparticles enter the human body, they are immediately confronted with the innate immune system, activating cellular mechanisms involved in the inflammatory process. These mechanisms comprise the expression and activation of proinflammatory cytokines, chemokines, and adhesion molecules, with the recruitment of inflammatory cells including basophils, macrophages, dendritic cells, T cells, neutrophils, monocytes, and eosinophils. Thus, further research is needed to establish the extent of such inflammatory response and safe exposure levels to nanoparticles.

The present Special Issue is devoted to gathering the current understanding of the interaction of nanoparticles with the immune system, through original research articles on the inflammatory response to nanomaterials and critical review articles that scrutinize the current knowledge in this area, providing an expert platform of discussion.

Dr. Marisa Freitas
Dr. Francesca Granucci
Dr. Daniela Ribeiro
Guest Editors

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Keywords

  • nanoparticles
  • immune system
  • inflammation
  • risk assessment

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Published Papers (8 papers)

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19 pages, 2993 KiB  
Article
In Vitro Evaluation of DSPE-PEG (5000) Amine SWCNT Toxicity and Efficacy as a Novel Nanovector Candidate in Photothermal Therapy by Response Surface Methodology (RSM)
by Naghmeh Hadidi, Niloufar Shahbahrami Moghadam, Gholamreza Pazuki, Parviz Parvin and Fatemeh Shahi
Cells 2021, 10(11), 2874; https://doi.org/10.3390/cells10112874 - 25 Oct 2021
Cited by 9 | Viewed by 2942
Abstract
Nowadays, finding a novel, effective, biocompatible, and minimally invasive cancer treatment is of great importance. One of the most promising research fields is the development of biocompatible photothermal nanocarriers. PTT (photothermal therapy) with an NIR (near-infrared) wavelength range (700–2000 nm) would cause cell [...] Read more.
Nowadays, finding a novel, effective, biocompatible, and minimally invasive cancer treatment is of great importance. One of the most promising research fields is the development of biocompatible photothermal nanocarriers. PTT (photothermal therapy) with an NIR (near-infrared) wavelength range (700–2000 nm) would cause cell death by increasing intercellular and intracellular temperature. PTT could also be helpful to overcome drug resistance during cancer treatments. In this study, an amine derivative of phospholipid poly ethylene glycol (DSPE-PEG (5000) amine) was conjugated with SWCNTs (single-walled carbon nanotubes) to reduce their intrinsic toxicity. Toxicity studies were performed on lung, liver, and ovarian cancer cell lines that were reported to show some degree of drug resistance to cisplatin. Toxicity results suggested that DSPE-PEG (5000) amine SWCNTs might be biocompatible photothermal nanocarriers in PTT. Therefore, our next step was to investigate the effect of DSPE-PEG (5000) amine SWCNT concentration, cell treatment time, and laser fluence on the apoptosis/necrosis of SKOV3 cells post-NIR exposure by RSM and experimental design software. It was concluded that photothermal efficacy and total apoptosis would be dose-dependent in terms of DSPE-PEG (5000) amine SWCNT concentration and fluence. Optimal solutions which showed the highest apoptosis and lowest necrosis were then achieved. Full article
(This article belongs to the Special Issue The Interaction of Biomedical Nanoparticles with the Immune System)
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16 pages, 2615 KiB  
Article
Glimepiride-Loaded Nanoemulgel; Development, In Vitro Characterization, Ex Vivo Permeation and In Vivo Antidiabetic Evaluation
by Fizza Abdul Razzaq, Muhammad Asif, Sajid Asghar, Muhammad Shahid Iqbal, Ikram Ullah Khan, Salah-Ud-Din Khan, Muhammad Irfan, Haroon Khalid Syed, Ahmed Khames, Hira Mahmood, Asim Y. Ibrahim and Amani M. El Sisi
Cells 2021, 10(9), 2404; https://doi.org/10.3390/cells10092404 - 13 Sep 2021
Cited by 25 | Viewed by 4083
Abstract
Glimepiride (GMP), an oral hypoglycemic agent is extensively employed in the treatment of type 2 diabetes. Transdermal delivery of GMP has been widely investigated as a promising alternative to an oral approach but the delivery of GMP is hindered owing to its low [...] Read more.
Glimepiride (GMP), an oral hypoglycemic agent is extensively employed in the treatment of type 2 diabetes. Transdermal delivery of GMP has been widely investigated as a promising alternative to an oral approach but the delivery of GMP is hindered owing to its low solubility and permeation. The present study was designed to formulate topical nanoemulgel GMP system and previously reported solubility enhanced glimepiride (GMP/βCD/GEL-44/16) in combination with anti-diabetic oil to enhance the hypoglycemic effect. Nanoemulsions were developed using clove oil, Tween-80, and PEG-400 and were gelled using xanthan gum (3%, w/w) to achieve the final nanoemulgel formulations. All of the formulations were evaluated in terms of particle size, zeta potential, pH, conductivity, viscosity, and in vitro skin permeation studies. In vivo hypoglycemic activity of the optimized nanoemulgel formulations was evaluated using a streptozocin-induced diabetes model. It was found that a synergistic combination of GMP with clove oil improved the overall drug permeation across the skin membrane and the hypoglycemic activity of GMP. The results showed that GMP/βCD/GEL-44/16-loaded nanoemulgel enhanced the in vitro skin permeation and improved the hypoglycemic activity in comparison with pure and marketed GMP. It is suggested that topical nano emulsion-based GMP gel and GMP/βCD/GEL-44/16 could be an effective alternative for oral therapy in the treatment of diabetes. Full article
(This article belongs to the Special Issue The Interaction of Biomedical Nanoparticles with the Immune System)
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18 pages, 4729 KiB  
Article
Graphene Oxide Nanosheets for Localized Hyperthermia—Physicochemical Characterization, Biocompatibility, and Induction of Tumor Cell Death
by Malgorzata J. Podolska, Alexandre Barras, Christoph Alexiou, Benjamin Frey, Udo Gaipl, Rabah Boukherroub, Sabine Szunerits, Christina Janko and Luis E. Muñoz
Cells 2020, 9(3), 776; https://doi.org/10.3390/cells9030776 - 23 Mar 2020
Cited by 24 | Viewed by 4053 | Correction
Abstract
Background: The main goals of cancer treatment are not only to eradicate the tumor itself but also to elicit a specific immune response that overcomes the resistance of tumor cells against chemo- and radiotherapies. Hyperthermia was demonstrated to chemo- and radio-sensitize cancerous cells. [...] Read more.
Background: The main goals of cancer treatment are not only to eradicate the tumor itself but also to elicit a specific immune response that overcomes the resistance of tumor cells against chemo- and radiotherapies. Hyperthermia was demonstrated to chemo- and radio-sensitize cancerous cells. Many reports have confirmed the immunostimulatory effect of such multi-modal routines. Methods: We evaluated the interaction of graphene oxide (GO) nanosheets; its derivatives reduced GO and PEGylated rGO, with components of peripheral blood and evaluated its thermal conductivity to induce cell death by localized hyperthermia. Results: We confirmed the sterility and biocompatibility of the graphene nanomaterials and demonstrated that hyperthermia applied alone or in the combination with radiotherapy induced much more cell death in tumor cells than irradiation alone. Cell death was confirmed by the release of lactate dehydrogenase from dead and dying tumor cells. Conclusion: Biocompatible GO and its derivatives can be successfully used in graphene-induced hyperthermia to elicit tumor cell death. Full article
(This article belongs to the Special Issue The Interaction of Biomedical Nanoparticles with the Immune System)
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21 pages, 2954 KiB  
Article
Loading of Primary Human T Lymphocytes with Citrate-Coated Superparamagnetic Iron Oxide Nanoparticles Does Not Impair Their Activation after Polyclonal Stimulation
by Marina Mühlberger, Harald Unterweger, Julia Band, Christian Lehmann, Lukas Heger, Diana Dudziak, Christoph Alexiou, Geoffrey Lee and Christina Janko
Cells 2020, 9(2), 342; https://doi.org/10.3390/cells9020342 - 1 Feb 2020
Cited by 16 | Viewed by 4772
Abstract
For the conversion of immunologically cold tumors, characterized by a low T cell infiltration, into hot tumors, it is necessary to enrich T cells in the tumor area. One possibility is the use of magnetic fields to direct T cells into the tumor. [...] Read more.
For the conversion of immunologically cold tumors, characterized by a low T cell infiltration, into hot tumors, it is necessary to enrich T cells in the tumor area. One possibility is the use of magnetic fields to direct T cells into the tumor. For this purpose, primary T cells that were freshly isolated from human whole blood were loaded with citrate-coated superparamagnetic iron oxide nanoparticles (SPIONCitrate). Cell toxicity and particle uptake were investigated by flow cytometry and atomic emission spectroscopy. The optimum loading of the T cells without any major effect on their viability was achieved with a particle concentration of 75 µg Fe/mL and a loading period of 24 h. The cellular content of SPIONCitrate was sufficient to attract these T cells with a magnet which was monitored by live-cell imaging. The functionality of the T cells was only slightly influenced by SPIONCitrate, as demonstrated by in vitro stimulation assays. The proliferation rate as well as the expression of co-stimulatory and inhibitory surface molecules (programmed cell death 1 (PD-1), lymphocyte activation gene 3 (LAG-3), T cell immunoglobulin and mucin domain containing 3 (Tim-3), C-C motif chemokine receptor 7 (CCR7), CD25, CD45RO, CD69) was investigated and found to be unchanged. Our results presented here demonstrate the feasibility of loading primary human T lymphocytes with superparamagnetic iron oxide nanoparticles without influencing their viability and functionality while achieving sufficient magnetizability for magnetically controlled targeting. Thus, the results provide a strong fundament for the transfer to tumor models and ultimately for new immunotherapeutic approaches for cancer treatment. Full article
(This article belongs to the Special Issue The Interaction of Biomedical Nanoparticles with the Immune System)
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17 pages, 1514 KiB  
Article
Gold Nanoparticles Modulate BCG-Induced Innate Immune Memory in Human Monocytes by Shifting the Memory Response towards Tolerance
by Benjamin J. Swartzwelter, Francesco Barbero, Alessandro Verde, Maria Mangini, Marinella Pirozzi, Anna Chiara De Luca, Victor F. Puntes, Luciana C. C. Leite, Paola Italiani and Diana Boraschi
Cells 2020, 9(2), 284; https://doi.org/10.3390/cells9020284 - 23 Jan 2020
Cited by 30 | Viewed by 5042
Abstract
Innate immune memory is characterized by a modulation in the magnitude with which innate immune cells such as monocytes and macrophages respond to potential dangers, subsequent to previous exposure to the same or unrelated agents. In this study, we have examined the capacity [...] Read more.
Innate immune memory is characterized by a modulation in the magnitude with which innate immune cells such as monocytes and macrophages respond to potential dangers, subsequent to previous exposure to the same or unrelated agents. In this study, we have examined the capacity of gold nanoparticles (AuNP), which are already in use for therapeutic and diagnostic purposes, to modulate the innate memory induced by bacterial agents. The induction of innate memory was achieved in vitro by exposing human primary monocytes to bacterial agents (lipopolysaccharide -LPS-, or live Bacille Calmette-Guérin -BCG) in the absence or presence of AuNP. After the primary activation, cells were allowed to return to a resting condition, and eventually re-challenged with LPS. The induction of memory was assessed by comparing the response to the LPS challenge of unprimed cells with that of cells primed with bacterial agents and AuNP. The response to LPS was measured as the production of inflammatory (TNFα, IL-6) and anti-inflammatory cytokines (IL-10, IL-1Ra). While ineffective in directly inducing innate memory per se, and unable to influence LPS-induced tolerance memory, AuNP significantly affected the memory response of BCG-primed cells, by inhibiting the secondary response in terms of both inflammatory and anti-inflammatory factor production. The reprogramming of BCG-induced memory towards a tolerance type of reactivity may open promising perspectives for the use of AuNP in immunomodulatory approaches to autoimmune and chronic inflammatory diseases. Full article
(This article belongs to the Special Issue The Interaction of Biomedical Nanoparticles with the Immune System)
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11 pages, 1905 KiB  
Article
CXCL5 Modified Nanoparticle Surface Improves CXCR2+ Cell Selective Internalization
by Roberta Cagliani, Francesca Gatto, Giulia Cibecchini, Roberto Marotta, Federico Catalano, Paola Sanchez-Moreno, Pier Paolo Pompa and Giuseppe Bardi
Cells 2020, 9(1), 56; https://doi.org/10.3390/cells9010056 - 24 Dec 2019
Cited by 8 | Viewed by 3184
Abstract
Driving nanomaterials to specific cell populations is still a major challenge for different biomedical applications. Several strategies to improve cell binding and uptake have been tried thus far by intrinsic material modifications or decoration with active molecules onto their surface. In the present [...] Read more.
Driving nanomaterials to specific cell populations is still a major challenge for different biomedical applications. Several strategies to improve cell binding and uptake have been tried thus far by intrinsic material modifications or decoration with active molecules onto their surface. In the present work, we covalently bound the chemokine CXCL5 on fluorescently labeled amino-functionalized SiO2 nanoparticles to precisely targeting CXCR2+ immune cells. We synthesized and precisely characterized the physicochemical features of the modified particles. The presence of CXCL5 on the surface was detected by z-potential variation and CXCL5-specific electron microscopy immunogold labeling. CXCL5-amino SiO2 nanoparticle cell binding and internalization performances were analyzed in CXCR2+ THP-1 cells by flow cytometry and confocal microscopy. We showed improved internalization of the chemokine modified particles in the absence or the presence of serum. This internalization was reduced by cell pre-treatment with free CXCL5. Furthermore, we demonstrated CXCR2+ cell preferential targeting by comparing particle uptake in THP-1 vs. low-CXCR2 expressing HeLa cells. Our results provide the proof of principle that chemokine decorated nanomaterials enhance uptake and allow precise cell subset localization. The possibility to aim at selective chemokine receptor-expressing cells can be beneficial for the diverse pathological conditions involving immune reactions. Full article
(This article belongs to the Special Issue The Interaction of Biomedical Nanoparticles with the Immune System)
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16 pages, 4309 KiB  
Article
Size Dependency of Circulation and Biodistribution of Biomimetic Nanoparticles: Red Blood Cell Membrane-Coated Nanoparticles
by Haichun Li, Kai Jin, Man Luo, Xuejun Wang, Xiaowen Zhu, Xianping Liu, Ting Jiang, Qin Zhang, Sheng Wang and Zhiqing Pang
Cells 2019, 8(8), 881; https://doi.org/10.3390/cells8080881 - 13 Aug 2019
Cited by 90 | Viewed by 6774
Abstract
Recently, biomimetic nanoparticles, especially cell membrane-cloaked nanoparticles, have attracted increasing attention in biomedical applications, including antitumor therapy, detoxification, and immune modulation, by imitating the structure and the function of biological systems such as long circulation life in the blood. However, the circulation time [...] Read more.
Recently, biomimetic nanoparticles, especially cell membrane-cloaked nanoparticles, have attracted increasing attention in biomedical applications, including antitumor therapy, detoxification, and immune modulation, by imitating the structure and the function of biological systems such as long circulation life in the blood. However, the circulation time of cell membrane-cloaked nanoparticles is far less than that of the original cells, greatly limiting their biomedical applications, while the underlying reasons are seldom demonstrated. In this study, the influence of particle size on the circulation and the biodistribution of red blood cell membrane-coated nanoparticles (RBC-NPs) as model biomimetic nanoparticles were investigated. Differently sized RBC-NPs (80, 120, 160, and 200 nm) were prepared by fusing RBC membranes on poly(lactic-co-glycolic acid) nanoparticles. It was shown that the particle size did not change the cellular uptake of these biomimetic nanoparticles by macrophage cells in vitro and their immunogenic responses in vivo. However, their circulation life in vivo decreased with the particle size, while their accumulation in the liver increased with the particle size, which might be related to their size-dependent filtration through hepatic sinusoids. These findings will provide experimental evidence for the design and the optimization of biomimetic nanoparticles. Full article
(This article belongs to the Special Issue The Interaction of Biomedical Nanoparticles with the Immune System)
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2 pages, 182 KiB  
Correction
Correction: Podolska et al. Graphene Oxide Nanosheets for Localized Hyperthermia—Physicochemical Characterization, Biocompatibility, and Induction of Tumor Cell Death. Cells 2020, 9, 776
by Malgorzata J. Podolska, Alexandre Barras, Christoph Alexiou, Benjamin Frey, Udo Gaipl, Rabah Boukherroub, Sabine Szunerits, Christina Janko and Luis E. Muñoz
Cells 2024, 13(23), 1927; https://doi.org/10.3390/cells13231927 - 21 Nov 2024
Viewed by 245
Abstract
Add New References [...] Full article
(This article belongs to the Special Issue The Interaction of Biomedical Nanoparticles with the Immune System)
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