Special Issue "Nanoparticle-Macrophage Interactions: Implications for Nanosafety and Nanomedicine"

A special issue of Nanomaterials (ISSN 2079-4991). This special issue belongs to the section "Biology and Medicines".

Deadline for manuscript submissions: closed (20 June 2021).

Special Issue Editors

Dr. Olesja Bondarenko
E-Mail Website1 Website2
Guest Editor
1. National Institute of Chemical Physics and Biophysics, Akadeemia tee 23, Tallinn 12618, Estonia;
2. University of Helsinki, HiLIFE unit Helsinki, Finland
Interests: nanoparticles; antibacterial nanoparticles; nanotoxicology; cell-nanoparticle interactions; nanoparticle-mediated drug delivery
Dr. Fernando Torres Andón
E-Mail Website
Guest Editor
1. Center for Research in Molecular Medicine & Chronic Diseases (CiMUS), Universidade de Santiago de Compostela, 15706 Campus Vida, Santiago de Compostela, Spain
2. IRCCS Istituto Clinico Humanitas, Via A. Manzoni 56, 20089 Rozzano, Milan, Italy
Interests: nanoparticles; macrophages; monocytes; innate immune system; immunotoxicity; cell death; surface functionalization; immunotherapy; macrophage-nanoparticle interaction

Special Issue Information

Dear colleagues,

Nanoparticles (NPs) offer unique physicochemical properties useful for biomedical applications, e.g., as antibacterials, vaccine adjuvants, and bioimaging and/or antitumoral agents. Medical use of NPs commonly implies their injection into the bloodstream, but other routes have been explored, such as the subcutaneous, oral, intranasal, inhalation or transdermal administration. Once in the body, NPs are inevitably recognized by the immune system. Macrophages are a major class of phagocytic innate immune cells, specializing in the neutralization and/or uptake of foreign material (including NPs) and consequent mounting of an immunological response. The mechanisms implicated in the uptake of NPs by macrophages determine the lifetime of NPs in relevant biological fluids or tissues, which has consequences for their nanosafety and biomedical applications. Various safe-by-design strategies, such as pegylation and other surface functionalizations of NPs, have been implemented to manipulate the recognition of NPs by monocytes/macrophages and, thus, their immunotoxicological properties. Of note, NPs have been also designed on purpose to target macrophages with the aim to trigger or to inhibit immune responses, for example, killing or reprogramming the tumor associated macrophages.

The aim of the current Special Issue is to cover recent advancements in our understanding of NP-macrophage interactions using in vitro, in vivo, and in silico approaches, novel strategies to control the toxicological and immunological profile of NPs, and innovative ways to modulate the delivery of NPs towards macrophages for safety and medical purposes.

Dr. Olesja Bondarenko
Dr. Fernando Torres Andón
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Nanomaterials is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2200 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • nanomaterials
  • macrophages
  • immunotoxicity
  • cytotoxicity
  • surface functionalization
  • macrophage–nanoparticle interaction

Published Papers (10 papers)

Order results
Result details
Select all
Export citation of selected articles as:

Editorial

Jump to: Research, Review

Editorial
Recent Discoveries in Nanoparticle–Macrophage Interactions: In Vitro Models for Nanosafety Testing and Novel Nanomedical Approaches for Immunotherapy
Nanomaterials 2021, 11(11), 2971; https://doi.org/10.3390/nano11112971 - 05 Nov 2021
Viewed by 310
Abstract
Nanoparticles (NPs) offer unique properties for biomedical applications, leading to new nanomedicines [...] Full article

Research

Jump to: Editorial, Review

Article
Profiling of Sub-Lethal in Vitro Effects of Multi-Walled Carbon Nanotubes Reveals Changes in Chemokines and Chemokine Receptors
Nanomaterials 2021, 11(4), 883; https://doi.org/10.3390/nano11040883 - 30 Mar 2021
Cited by 2 | Viewed by 673
Abstract
Engineered nanomaterials are potentially very useful for a variety of applications, but studies are needed to ascertain whether these materials pose a risk to human health. Here, we studied three benchmark nanomaterials (Ag nanoparticles, TiO2 nanoparticles, and multi-walled carbon nanotubes, MWCNTs) procured [...] Read more.
Engineered nanomaterials are potentially very useful for a variety of applications, but studies are needed to ascertain whether these materials pose a risk to human health. Here, we studied three benchmark nanomaterials (Ag nanoparticles, TiO2 nanoparticles, and multi-walled carbon nanotubes, MWCNTs) procured from the nanomaterial repository at the Joint Research Centre of the European Commission. Having established a sub-lethal concentration of these materials using two human cell lines representative of the immune system and the lungs, respectively, we performed RNA sequencing of the macrophage-like cell line after exposure for 6, 12, and 24 h. Downstream analysis of the transcriptomics data revealed significant effects on chemokine signaling pathways. CCR2 was identified as the most significantly upregulated gene in MWCNT-exposed cells. Using multiplex assays to evaluate cytokine and chemokine secretion, we could show significant effects of MWCNTs on several chemokines, including CCL2, a ligand of CCR2. The results demonstrate the importance of evaluating sub-lethal concentrations of nanomaterials in relevant target cells. Full article
Show Figures

Figure 1

Article
Serum Lowers Bioactivity and Uptake of Synthetic Amorphous Silica by Alveolar Macrophages in a Particle Specific Manner
Nanomaterials 2021, 11(3), 628; https://doi.org/10.3390/nano11030628 - 03 Mar 2021
Cited by 2 | Viewed by 560
Abstract
Various cell types are compromised by synthetic amorphous silica (SAS) if they are exposed to SAS under protein-free conditions in vitro. Addition of serum protein can mitigate most SAS effects, but it is not clear whether this is solely caused by protein corona [...] Read more.
Various cell types are compromised by synthetic amorphous silica (SAS) if they are exposed to SAS under protein-free conditions in vitro. Addition of serum protein can mitigate most SAS effects, but it is not clear whether this is solely caused by protein corona formation and/or altered particle uptake. Because sensitive and reliable mass spectrometric measurements of SiO2 NP are cumbersome, quantitative uptake studies of SAS at the cellular level are largely missing. In this study, we combined the comparison of SAS effects on alveolar macrophages in the presence and absence of foetal calf serum with mass spectrometric measurement of 28Si in alkaline cell lysates. Effects on the release of lactate dehydrogenase, glucuronidase, TNFα and H2O2 of precipitated (SIPERNAT® 50, SIPERNAT® 160) and fumed SAS (AEROSIL® OX50, AEROSIL® 380 F) were lowered close to control level by foetal calf serum (FCS) added to the medium. Using a quantitative high resolution ICP-MS measurement combined with electron microscopy, we found that FCS reduced the uptake of particle mass by 9.9% (SIPERNAT® 50) up to 83.8% (AEROSIL® OX50). Additionally, larger particle agglomerates were less frequent in cells in the presence of FCS. Plotting values for lactate dehydrogenase (LDH), glucuronidase (GLU) or tumour necrosis factor alpha (TNFα) against the mean cellular dose showed the reduction of bioactivity with a particle sedimentation bias. As a whole, the mitigating effects of FCS on precipitated and fumed SAS on alveolar macrophages are caused by a reduction of bioactivity and by a lowered internalization, and both effects occur in a particle specific manner. The method to quantify nanosized SiO2 in cells is a valuable tool for future in vitro studies. Full article
Show Figures

Graphical abstract

Article
Scavenger Receptor A1 Mediates the Uptake of Carboxylated and Pristine Multi-Walled Carbon Nanotubes Coated with Bovine Serum Albumin
Nanomaterials 2021, 11(2), 539; https://doi.org/10.3390/nano11020539 - 20 Feb 2021
Cited by 1 | Viewed by 943
Abstract
Previously, we noted that carboxylated multi-walled carbon nanotubes (cMWNTs) coated with Pluronic® F-108 (PF108) bound to and were accumulated by macrophages, but that pristine multi-walled carbon nanotubes (pMWNTs) coated with PF108 were not (Wang et al., Nanotoxicology2018, 12, 677). [...] Read more.
Previously, we noted that carboxylated multi-walled carbon nanotubes (cMWNTs) coated with Pluronic® F-108 (PF108) bound to and were accumulated by macrophages, but that pristine multi-walled carbon nanotubes (pMWNTs) coated with PF108 were not (Wang et al., Nanotoxicology2018, 12, 677). Subsequent studies with Chinese hamster ovary (CHO) cells that overexpressed scavenger receptor A1 (SR-A1) and with macrophages derived from mice knocked out for SR-A1 provided evidence that SR-A1 was a receptor of PF108-cMWNTs (Wang et al., Nanomaterials (Basel) 2020, 10, 2417). Herein, we replaced the PF108 coat with bovine serum albumin (BSA) to investigate how a BSA corona affected the interaction of multi-walled carbon nanotubes (MWNTs) with cells. Both BSA-coated cMWNTs and pMWNTs bound to and were accumulated by RAW 264.7 macrophages, although the cells bound two times more BSA-coated cMWNT than pMWNTs. RAW 264.7 cells that were deleted for SR-A1 using CRISPR-Cas9 technology had markedly reduced binding and accumulation of both BSA-coated cMWNTs and pMWNTs, suggesting that SR-A1 was responsible for the uptake of both MWNT types. Moreover, CHO cells that ectopically expressed SR-A1 accumulated both MWNT types, whereas wild-type CHO cells did not. One model to explain these results is that SR-A1 can interact with two structural features of BSA-coated cMWNTs, one inherent to the oxidized nanotubes (such as COOH and other oxidized groups) and the other provided by the BSA corona; whereas SR-A1 only interacts with the BSA corona of BSA-pMWNTs. Full article
Show Figures

Graphical abstract

Article
Interaction between Macrophages and Nanoparticles: In Vitro 3D Cultures for the Realistic Assessment of Inflammatory Activation and Modulation of Innate Memory
Nanomaterials 2021, 11(1), 207; https://doi.org/10.3390/nano11010207 - 15 Jan 2021
Cited by 6 | Viewed by 979
Abstract
Understanding the modes of interaction between human monocytes/macrophages and engineered nanoparticles is the basis for assessing particle safety, in terms of activation of innate/inflammatory reactions, and their possible exploitation for medical applications. In vitro assessment of nanoparticle-macrophage interaction allows for examining the response [...] Read more.
Understanding the modes of interaction between human monocytes/macrophages and engineered nanoparticles is the basis for assessing particle safety, in terms of activation of innate/inflammatory reactions, and their possible exploitation for medical applications. In vitro assessment of nanoparticle-macrophage interaction allows for examining the response of primary human cells, but the conventional 2D cultures do not reproduce the three-dimensional spacing of a tissue and the interaction of macrophages with the extracellular tissue matrix, conditions that shape macrophage recognition capacity and reactivity. Here, we have compared traditional 2D cultures with cultures on a 3D collagen matrix for evaluating the capacity gold nanoparticles to induce monocyte activation and subsequent innate memory in human blood monocytes in comparison to bacterial LPS. Results show that monocytes react to stimuli almost in the same way in 2D and 3D cultures in terms of production of TNFα and IL-6, but that notable differences are found when IL-8 and IL-1Ra are examined, in particular in the recall/memory response of primed cells to a second stimulation, with the 3D cultures showing cell activation and memory effects of nanoparticles better. In addition, the response variations in monocytes/macrophages from different donors point towards a personalized assessment of the nanoparticle effects on macrophage activation. Full article
Show Figures

Figure 1

Article
Selective Uptake of Carboxylated Multi-Walled Carbon Nanotubes by Class A Type 1 Scavenger Receptors and Impaired Phagocytosis in Alveolar Macrophages
Nanomaterials 2020, 10(12), 2417; https://doi.org/10.3390/nano10122417 - 03 Dec 2020
Cited by 5 | Viewed by 653
Abstract
The production and applications of multi-walled carbon nanotubes (MWNTs) have increased despite evidence that MWNTs can be toxic. Recently, we reported that the binding of Pluronic® F-108 (PF108)-coated carboxylated MWNTs (C-MWNTs) to macrophages is inhibited by class A scavenger receptors (SR-As) antagonists [...] Read more.
The production and applications of multi-walled carbon nanotubes (MWNTs) have increased despite evidence that MWNTs can be toxic. Recently, we reported that the binding of Pluronic® F-108 (PF108)-coated carboxylated MWNTs (C-MWNTs) to macrophages is inhibited by class A scavenger receptors (SR-As) antagonists (R. Wang et al., 2018. Nanotoxicology 12:677–690). The current study investigates the uptake of PF108-coated MWNTs by macrophages lacking SR-A1 and by CHO cells that ectopically express SR-A1. Macrophages without SR-A1 failed to take up C-MWNTs and CHO cells that expressed SR-A1 did take up C-MWNTs, but not pristine MWNTs (P-MWNTs) or amino-functionalized MWNTs (N-MWNTs). The dependence of C-MWNT uptake on SR-A1 is strong evidence that SR-A1 is a receptor for C-MWNTs. The consequences of SR-A1-dependent C-MWNT accumulation on cell viability and phagocytic activity in macrophages were also studied. C-MWNTs were more toxic than P-MWNTs and N-MWNTs in cell proliferation and colony formation tests. C-MWNTs reduced surface SR-A1 levels in RAW 264.7 cells and impaired phagocytic uptake of three known SR-A1 ligands, polystyrene beads, heat-killed E. coli, and oxLDL. Altogether, results of this study confirmed that SR-A1 receptors are important for the selective uptake of PF108-coated C-MWNTs and that accumulation of the C-MWNTs impairs phagocytic activity and cell viability in macrophages. Full article
Show Figures

Graphical abstract

Article
Rifabutin-Loaded Nanostructured Lipid Carriers as a Tool in Oral Anti-Mycobacterial Treatment of Crohn’s Disease
Nanomaterials 2020, 10(11), 2138; https://doi.org/10.3390/nano10112138 - 27 Oct 2020
Cited by 1 | Viewed by 889
Abstract
Oral anti-mycobacterial treatment of Crohn’s disease (CD) is limited by the low aqueous solubility of drugs, along with the altered gut conditions of patients, making uncommon their clinical use. Hence, the aim of the present work is focused on the in vitro evaluation [...] Read more.
Oral anti-mycobacterial treatment of Crohn’s disease (CD) is limited by the low aqueous solubility of drugs, along with the altered gut conditions of patients, making uncommon their clinical use. Hence, the aim of the present work is focused on the in vitro evaluation of rifabutin (RFB)-loaded Nanostructured lipid carriers (NLC), in order to solve limitations associated to this therapeutic approach. RFB-loaded NLC were prepared by hot homogenization and characterized in terms of size, polydispersity, surface charge, morphology, thermal stability, and drug payload and release. Permeability across Caco-2 cell monolayers and cytotoxicity and uptake in human macrophages was also determined. NLC obtained were nano-sized, monodisperse, negatively charged, and spheroidal-shaped, showing a suitable drug payload and thermal stability. Furthermore, the permeability profile, macrophage uptake and selective intracellular release of RFB-loaded NLC, guarantee an effective drug dose administration to cells. Outcomes suggest that rifabutin-loaded NLC constitute a promising strategy to improve oral anti-mycobacterial therapy in Crohn’s disease. Full article
Show Figures

Graphical abstract

Article
Overcoming the Inflammatory Stage of Non-Healing Wounds: In Vitro Mechanism of Action of Negatively Charged Microspheres (NCMs)
Nanomaterials 2020, 10(6), 1108; https://doi.org/10.3390/nano10061108 - 03 Jun 2020
Cited by 3 | Viewed by 1101
Abstract
Negatively charged microspheres (NCMs) represent a new therapeutic approach for wound healing since recent clinical trials have shown NCM efficacy in the recovery of hard-to-heal wounds that tend to stay in the inflammatory phase, unlocking the healing process. The aim of this study [...] Read more.
Negatively charged microspheres (NCMs) represent a new therapeutic approach for wound healing since recent clinical trials have shown NCM efficacy in the recovery of hard-to-heal wounds that tend to stay in the inflammatory phase, unlocking the healing process. The aim of this study was to elucidate the NCM mechanism of action. NCMs were extracted from a commercial microsphere formulation (PolyHeal® Micro) and cytotoxicity, attachment, proliferation and viability assays were performed in keratinocytes and dermal fibroblasts, while macrophages were used for the phagocytosis and polarization assays. We demonstrated that cells tend to attach to the microsphere surface, and that NCMs are biocompatible and promote cell proliferation at specific concentrations (50 and 10 NCM/cell) by a minimum of 3 fold compared to the control group. Furthermore, NCM internalization by macrophages seemed to drive these cells to a noninflammatory condition, as demonstrated by the over-expression of CD206 and the under-expression of CD64, M2 and M1 markers, respectively. NCMs are an effective approach for reverting the chronic inflammatory state of stagnant wounds (such as diabetic wounds) and thus for improving wound healing. Full article
Show Figures

Figure 1

Review

Jump to: Editorial, Research

Review
Zebrafish Models for the Safety and Therapeutic Testing of Nanoparticles with a Focus on Macrophages
Nanomaterials 2021, 11(7), 1784; https://doi.org/10.3390/nano11071784 - 09 Jul 2021
Cited by 4 | Viewed by 1164
Abstract
New nanoparticles and biomaterials are increasingly being used in biomedical research for drug delivery, diagnostic applications, or vaccines, and they are also present in numerous commercial products, in the environment and workplaces. Thus, the evaluation of the safety and possible therapeutic application of [...] Read more.
New nanoparticles and biomaterials are increasingly being used in biomedical research for drug delivery, diagnostic applications, or vaccines, and they are also present in numerous commercial products, in the environment and workplaces. Thus, the evaluation of the safety and possible therapeutic application of these nanomaterials has become of foremost importance for the proper progress of nanotechnology. Due to economical and ethical issues, in vitro and in vivo methods are encouraged for the testing of new compounds and/or nanoparticles, however in vivo models are still needed. In this scenario, zebrafish (Danio rerio) has demonstrated potential for toxicological and pharmacological screenings. Zebrafish presents an innate immune system, from early developmental stages, with conserved macrophage phenotypes and functions with respect to humans. This fact, combined with the transparency of zebrafish, the availability of models with fluorescently labelled macrophages, as well as a broad variety of disease models offers great possibilities for the testing of new nanoparticles. Thus, with a particular focus on macrophage–nanoparticle interaction in vivo, here, we review the studies using zebrafish for toxicological and biodistribution testing of nanoparticles, and also the possibilities for their preclinical evaluation in various diseases, including cancer and autoimmune, neuroinflammatory, and infectious diseases. Full article
Show Figures

Graphical abstract

Review
Therapeutic Manipulation of Macrophages Using Nanotechnological Approaches for the Treatment of Osteoarthritis
Nanomaterials 2020, 10(8), 1562; https://doi.org/10.3390/nano10081562 - 09 Aug 2020
Cited by 5 | Viewed by 1624
Abstract
Osteoarthritis (OA) is the most common joint pathology causing severe pain and disability. Macrophages play a central role in the pathogenesis of OA. In the joint microenvironment, macrophages with an M1-like pro-inflammatory phenotype induce chronic inflammation and joint destruction, and they have been [...] Read more.
Osteoarthritis (OA) is the most common joint pathology causing severe pain and disability. Macrophages play a central role in the pathogenesis of OA. In the joint microenvironment, macrophages with an M1-like pro-inflammatory phenotype induce chronic inflammation and joint destruction, and they have been correlated with the development and progression of the disease, while the M2-like anti-inflammatory macrophages support the recovery of the disease, promoting tissue repair and the resolution of inflammation. Nowadays, the treatment of OA in the clinic relies on systemic and/or intra-articular administration of anti-inflammatory and pain relief drugs, as well as surgical interventions for the severe cases (i.e., meniscectomy). The disadvantages of the pharmacological therapy are related to the chronic nature of the disease, requiring prolonged treatments, and to the particular location of the pathology in joint tissues, which are separated anatomical compartments with difficult access for the drugs. To overcome these challenges, nanotechnological approaches have been investigated to improve the delivery of drugs toward macrophages into the diseased joint. This strategy may offer advantages by reducing off-target toxicities and improving long-term therapeutic efficacy. In this review, we describe the nanomaterial-based approaches designed so far to directly or indirectly manipulate macrophages for the treatment of osteoarthritis. Full article
Show Figures

Figure 1

Back to TopTop