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Pharmaceutics
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Nanoparticles for Targeting and Treating Macrophages
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Nanoparticles for Targeting and Treating Macrophages

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Biologics and Biosimilars".

Deadline for manuscript submissions: closed (31 March 2023) | Viewed by 22024

Special Issue Editor

Dr. Pedro Melgar-Lesmes

E-Mail Website
Guest Editor
1. Department of Biomedicine, University of Barcelona, 08007 Barcelona, Spain
2. August Pi i Sunyer Biomedical Research Institute (IDIBAPS), 08036 Barcelona, Spain
3. Institute for Medical Engineering and Science, MIT, Cambridge, MA 02139, USA
Interests: nanoparticles; macrophages; liver; regeneration; fibrosis; inflammation

Special Issue Information

Dear Colleagues,

Nanoparticles are nanomaterials with three external nanoscale dimensions with tunable physical, chemical, and biological characteristics. Regardless of the nanomaterial composition, macrophages can detect and incorporate these foreign bodies by phagocytosis. Recent investigations are taking advantage of this biological fact to design nanoparticles for specific macrophage targeting and treatment in a wide array of diseases. Macrophages are plastic cells from the innate immune system that play different roles in the development, homeostasis, tissue repair and immune response. Indeed, macrophage modulation is of vital importance in chronic inflammation, fibrosis, wound healing, and cancer. Nanoparticles can be modified by the addition of ligands to achieve specific macrophage targeting for drug or gene therapy. They can also be integrated in hydrogels or medical devices to attract and modulate macrophages and the innate immune response. The aim of this issue is to uncover all the different strategies to use nanoparticles to target and modulate macrophages.

As the Guest Editor of the Pharmaceutics Special Issue entitled “Nanoparticles for Targeting and Treating Macrophages”, I would like to cordially invite you to contribute with a research article or a review paper to this Issue due to your excellent contributions to this field. This Special Issue aims to uncover all the different strategies to use nanoparticles to target and treat macrophages.

In this Special Issue, original research articles and reviews are welcome. Research areas may include (but not limited to) the following: Nanoscale colloidal systems, nanomaterials, hydrogels, or devices incorporating nanoparticles designed to target and treat macrophages.

I look forward to receiving your contributions. 

Dr. Pedro Melgar-Lesmes
Guest Editor

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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. Pharmaceutics 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 2900 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

  • nanoparticles
  • macrophages
  • targeting
  • inflammation
  • fibrosis
  • wound healing
  • regeneration
  • hydrogels
  • cancer
  • devices

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Published Papers (7 papers)

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Research

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21 pages, 8030 KiB  
Article
A Reversibly Thermoresponsive, Theranostic Nanoemulgel for Tacrolimus Delivery to Activated Macrophages: Formulation and In Vitro Validation
by Riddhi Vichare, Caitlin Crelli, Lu Liu, Amit Chandra Das, Rebecca McCallin, Fatih Zor, Yalcin Kulahci, Vijay S. Gorantla and Jelena M. Janjic
Pharmaceutics 2023, 15(10), 2372; https://doi.org/10.3390/pharmaceutics15102372 - 22 Sep 2023
Cited by 5 | Viewed by 2091
Abstract
Despite long-term immunosuppression, organ transplant recipients face the risk of immune rejection and graft loss. Tacrolimus (TAC, FK506, Prograf®) is an FDA-approved keystone immunosuppressant for preventing transplant rejection. However, it undergoes extensive first-pass metabolism and has a narrow therapeutic window, which [...] Read more.
Despite long-term immunosuppression, organ transplant recipients face the risk of immune rejection and graft loss. Tacrolimus (TAC, FK506, Prograf®) is an FDA-approved keystone immunosuppressant for preventing transplant rejection. However, it undergoes extensive first-pass metabolism and has a narrow therapeutic window, which leads to erratic bioavailability and toxicity. Local delivery of TAC directly into the graft, instead of systemic delivery, can improve safety, efficacy, and tolerability. Macrophages have emerged as promising therapeutic targets as their increased levels correlate with an increased risk of organ rejection and a poor prognosis post-transplantation. Here, we present a locally injectable drug delivery platform for macrophages, where TAC is incorporated into a colloidally stable nanoemulsion and then formulated as a reversibly thermoresponsive, pluronic-based nanoemulgel (NEG). This novel formulation is designed to undergo a sol-to-gel transition at physiological temperature to sustain TAC release in situ at the site of local application. We also show that TAC-NEG mitigates the release of proinflammatory cytokines and nitric oxide from lipopolysaccharide (LPS)-activated macrophages. To the best of our knowledge, this is the first TAC-loaded nanoemulgel with demonstrated anti-inflammatory effects on macrophages in vitro. Full article
(This article belongs to the Special Issue Nanoparticles for Targeting and Treating Macrophages)
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19 pages, 12321 KiB  
Article
Nanostructured Microparticles Repolarize Macrophages and Induce Cell Death in an In Vitro Model of Tumour-Associated Macrophages
by Salma Al-Fityan, Britta Diesel, Thorben Fischer, Emmanuel Ampofo, Annika Schomisch, Vida Mashayekhi, Marc Schneider and Alexandra K. Kiemer
Pharmaceutics 2023, 15(7), 1895; https://doi.org/10.3390/pharmaceutics15071895 - 5 Jul 2023
Cited by 2 | Viewed by 2139
Abstract
Macrophages (MΦs) in their pro-inflammatory state (M1) suppress tumour growth, while tumour-associated MΦs (TAMs) can promote tumour progression. The aim of this study was to test the hypothesis that targeted delivery of the immune activator poly(I:C) in aspherical silica microrods (µRs) can repolarize [...] Read more.
Macrophages (MΦs) in their pro-inflammatory state (M1) suppress tumour growth, while tumour-associated MΦs (TAMs) can promote tumour progression. The aim of this study was to test the hypothesis that targeted delivery of the immune activator poly(I:C) in aspherical silica microrods (µRs) can repolarize TAMs into M1-like cells. µRs (10 µm × 3 µm) were manufactured from silica nanoparticles and stabilized with dextran sulphate and polyethyleneimine. The THP-1 cell line, differentiated into MΦs, and primary human monocyte-derived MΦs (HMDMs) were treated with tumour-cell-conditioned medium (A549), but only HMDMs could be polarized towards TAMs. Flow cytometry and microscopy revealed elevated uptake of µRs by TAMs compared to non-polarized HMDMs. Flow cytometry and qPCR studies on polarization markers showed desirable effects of poly(I:C)-loaded MPs towards an M1 polarization. However, unloaded µRs also showed distinct actions, which were not induced by bacterial contaminations. Reporter cell assays showed that µRs induce the secretion of the inflammatory cytokine IL-1β. Macrophages from Nlrp3 knockout mice showed that µRs in concentrations as low as 0.5 µR per cell can activate the inflammasome and induce cell death. In conclusion, our data show that µRs, even if unloaded, can induce inflammasome activation and cell death in low concentrations. Full article
(This article belongs to the Special Issue Nanoparticles for Targeting and Treating Macrophages)
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16 pages, 2455 KiB  
Article
PPAR-γ Agonist GW1929 Targeted to Macrophages with Dendrimer–Graphene Nanostars Reduces Liver Fibrosis and Inflammation
by Alazne Moreno-Lanceta, Mireia Medrano-Bosch, Blanca Simón-Codina, Montserrat Barber-González, Wladimiro Jiménez and Pedro Melgar-Lesmes
Pharmaceutics 2023, 15(5), 1452; https://doi.org/10.3390/pharmaceutics15051452 - 10 May 2023
Cited by 9 | Viewed by 2676
Abstract
Macrophages play essential roles during the progression of chronic liver disease. They actively participate in the response to liver damage and in the balance between fibrogenesis and regression. The activation of the PPARγ nuclear receptor in macrophages has traditionally been associated with an [...] Read more.
Macrophages play essential roles during the progression of chronic liver disease. They actively participate in the response to liver damage and in the balance between fibrogenesis and regression. The activation of the PPARγ nuclear receptor in macrophages has traditionally been associated with an anti-inflammatory phenotype. However, there are no PPARγ agonists with high selectivity for macrophages, and the use of full agonists is generally discouraged due to severe side effects. We designed dendrimer–graphene nanostars linked to a low dose of the GW1929 PPARγ agonist (DGNS-GW) for the selective activation of PPARγ in macrophages in fibrotic livers. DGNS-GW preferentially accumulated in inflammatory macrophages in vitro and attenuated macrophage pro-inflammatory phenotype. The treatment with DGNS-GW in fibrotic mice efficiently activated liver PPARγ signaling and promoted a macrophage switch from pro-inflammatory M1 to anti-inflammatory M2 phenotype. The reduction of hepatic inflammation was associated with a significant reduction in hepatic fibrosis but did not alter liver function or hepatic stellate cell activation. The therapeutic antifibrotic utility of DGNS-GW was attributed to an increased expression of hepatic metalloproteinases that allowed extracellular matrix remodeling. In conclusion, the selective activation of PPARγ in hepatic macrophages with DGNS-GW significantly reduced hepatic inflammation and stimulated extracellular matrix remodeling in experimental liver fibrosis. Full article
(This article belongs to the Special Issue Nanoparticles for Targeting and Treating Macrophages)
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17 pages, 2959 KiB  
Article
Poly(β-amino ester)s-Based Delivery Systems for Targeted Transdermal Vaccination
by Núria Puigmal, Víctor Ramos, Natalie Artzi and Salvador Borrós
Pharmaceutics 2023, 15(4), 1262; https://doi.org/10.3390/pharmaceutics15041262 - 17 Apr 2023
Cited by 8 | Viewed by 3368
Abstract
Nucleic acid vaccines have become a transformative technology to fight emerging infectious diseases and cancer. Delivery of such via the transdermal route could boost their efficacy given the complex immune cell reservoir present in the skin that is capable of engendering robust immune [...] Read more.
Nucleic acid vaccines have become a transformative technology to fight emerging infectious diseases and cancer. Delivery of such via the transdermal route could boost their efficacy given the complex immune cell reservoir present in the skin that is capable of engendering robust immune responses. We have generated a novel library of vectors derived from poly(β-amino ester)s (PBAEs) including oligopeptide-termini and a natural ligand, mannose, for targeted transfection of antigen presenting cells (APCs) such as Langerhans cells and macrophages in the dermal milieu. Our results reaffirmed terminal decoration of PBAEs with oligopeptide chains as a powerful tool to induce cell-specific transfection, identifying an outstanding candidate with a ten-fold increased transfection efficiency over commercial controls in vitro. The inclusion of mannose in the PBAE backbone rendered an additive effect and increased transfection levels, achieving superior gene expression in human monocyte-derived dendritic cells and other accessory antigen presenting cells. Moreover, top performing candidates were capable of mediating surface gene transfer when deposited as polyelectrolyte films onto transdermal devices such as microneedles, offering alternatives to conventional hypodermic administration. We predict that the use of highly efficient delivery vectors derived from PBAEs could advance clinical translation of nucleic acid vaccination over protein- and peptide-based strategies. Full article
(This article belongs to the Special Issue Nanoparticles for Targeting and Treating Macrophages)
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Review

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34 pages, 1777 KiB  
Review
A Current Update on the Role of HDL-Based Nanomedicine in Targeting Macrophages in Cardiovascular Disease
by Alankrita Rani and Gunther Marsche
Pharmaceutics 2023, 15(5), 1504; https://doi.org/10.3390/pharmaceutics15051504 - 15 May 2023
Cited by 8 | Viewed by 4558
Abstract
High-density lipoproteins (HDL) are complex endogenous nanoparticles involved in important functions such as reverse cholesterol transport and immunomodulatory activities, ensuring metabolic homeostasis and vascular health. The ability of HDL to interact with a plethora of immune cells and structural cells places it in [...] Read more.
High-density lipoproteins (HDL) are complex endogenous nanoparticles involved in important functions such as reverse cholesterol transport and immunomodulatory activities, ensuring metabolic homeostasis and vascular health. The ability of HDL to interact with a plethora of immune cells and structural cells places it in the center of numerous disease pathophysiologies. However, inflammatory dysregulation can lead to pathogenic remodeling and post-translational modification of HDL, rendering HDL dysfunctional or even pro-inflammatory. Monocytes and macrophages play a critical role in mediating vascular inflammation, such as in coronary artery disease (CAD). The fact that HDL nanoparticles have potent anti-inflammatory effects on mononuclear phagocytes has opened new avenues for the development of nanotherapeutics to restore vascular integrity. HDL infusion therapies are being developed to improve the physiological functions of HDL and to quantitatively restore or increase the native HDL pool. The components and design of HDL-based nanoparticles have evolved significantly since their initial introduction with highly anticipated results in an ongoing phase III clinical trial in subjects with acute coronary syndrome. The understanding of mechanisms involved in HDL-based synthetic nanotherapeutics is critical to their design, therapeutic potential and effectiveness. In this review, we provide a current update on HDL-ApoA-I mimetic nanotherapeutics, highlighting the scope of treating vascular diseases by targeting monocytes and macrophages. Full article
(This article belongs to the Special Issue Nanoparticles for Targeting and Treating Macrophages)
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28 pages, 4816 KiB  
Review
Targeting Tumor-Associated Macrophages for Imaging
by Jiahao Hu, Xiaoling Xu and Yongzhong Du
Pharmaceutics 2023, 15(1), 144; https://doi.org/10.3390/pharmaceutics15010144 - 31 Dec 2022
Cited by 2 | Viewed by 3001
Abstract
As an important component of the tumor immune microenvironment (TIME), tumor-associated macrophages (TAMs) occupy a significant niche in tumor margin aggregation and respond to changes in the TIME. Thus, targeting TAMs is important for tumor monitoring, surgical guidance and efficacy evaluation. Continuously developing [...] Read more.
As an important component of the tumor immune microenvironment (TIME), tumor-associated macrophages (TAMs) occupy a significant niche in tumor margin aggregation and respond to changes in the TIME. Thus, targeting TAMs is important for tumor monitoring, surgical guidance and efficacy evaluation. Continuously developing nanoprobes and imaging agents paves the way toward targeting TAMs for precise imaging and diagnosis. This review summarizes the commonly used nanomaterials for TAM targeting imaging probes, including metal-based nanoprobes (iron, manganese, gold, silver), fluorine-19-based nanoprobes, radiolabeled agents, near-infrared fluorescence dyes and ultrasonic nanobubbles. Additionally, the prospects and challenges of designing nanomaterials for imaging and diagnosis (targeting efficiency, pharmacokinetics, and surgery guidance) are described in this review. Notwithstanding, TAM-targeting nanoplatforms provide great potential for imaging, diagnosis and therapy with a greater possibility of clinical transformation. Full article
(This article belongs to the Special Issue Nanoparticles for Targeting and Treating Macrophages)
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25 pages, 10993 KiB  
Review
Modulation of Macrophages Using Nanoformulations with Curcumin to Treat Inflammatory Diseases: A Concise Review
by Huxiao Sun, Mengsi Zhan, Serge Mignani, Dzmitry Shcharbin, Jean-Pierre Majoral, João Rodrigues, Xiangyang Shi and Mingwu Shen
Pharmaceutics 2022, 14(10), 2239; https://doi.org/10.3390/pharmaceutics14102239 - 20 Oct 2022
Cited by 13 | Viewed by 3211
Abstract
Curcumin (Cur), a traditional Chinese medicine extracted from natural plant rhizomes, has become a candidate drug for the treatment of diseases due to its anti-inflammatory, anticancer, antioxidant, and antibacterial activities. However, the poor water solubility and low bioavailability of Cur limit its therapeutic [...] Read more.
Curcumin (Cur), a traditional Chinese medicine extracted from natural plant rhizomes, has become a candidate drug for the treatment of diseases due to its anti-inflammatory, anticancer, antioxidant, and antibacterial activities. However, the poor water solubility and low bioavailability of Cur limit its therapeutic effects for clinical applications. A variety of nanocarriers have been successfully developed to improve the water solubility, in vivo distribution, and pharmacokinetics of Cur, as well as to enhance the ability of Cur to polarize macrophages and relieve macrophage oxidative stress or anti-apoptosis, thus accelerating the therapeutic effects of Cur on inflammatory diseases. Herein, we review the design and development of diverse Cur nanoformulations in recent years and introduce the biomedical applications and potential therapeutic mechanisms of Cur nanoformulations in common inflammatory diseases, such as arthritis, neurodegenerative diseases, respiratory diseases, and ulcerative colitis, by regulating macrophage behaviors. Finally, the perspectives of the design and preparation of future nanocarriers aimed at efficiently exerting the biological activity of Cur are briefly discussed. Full article
(This article belongs to the Special Issue Nanoparticles for Targeting and Treating Macrophages)
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