Liver fibrosis affects the targeting properties of drug delivery systems to macrophage subsets in vivo

Can Ergen, Patricia Maria Niemietz, Felix Heymann, Maike Baues, Felix Gremse, Robert Pola, Louis van Bloois, Gert Storm, Fabian Kiessling, Christian Trautwein, Tom Luedde, Twan Lammers, Frank Tacke (Corresponding Author)

Research output: Contribution to journalArticleAcademicpeer-review

1 Citation (Scopus)

Abstract

Myeloid immune cells promote inflammation and fibrosis in chronic liver diseases. Drug delivery systems, such as polymers, liposomes and microbubbles, efficiently target myeloid cells in healthy liver, but their targeting properties in hepatic fibrosis remain elusive. We therefore studied the biodistribution of three intravenously injected carrier material, i.e. 10 nm poly(N-(2-hydroxypropyl)methacrylamide) polymers, 100 nm PEGylated liposomes and 2000 nm poly(butyl cyanoacrylate) microbubbles, in two fibrosis models in immunocompetent mice. While whole-body imaging confirmed preferential hepatic uptake even after induction of liver fibrosis, flow cytometry and immunofluorescence analysis revealed markedly decreased carrier uptake by liver macrophage subsets in fibrosis, particularly for microbubbles and polymers. Importantly, carrier uptake co-localized with immune infiltrates in fibrotic livers, corroborating the intrinsic ability of the carriers to target myeloid cells in areas of inflammation. Of the tested carrier systems liposomes had the highest uptake efficiency among hepatic myeloid cells, but the lowest specificity for cellular subsets. Hepatic fibrosis affected carrier uptake in liver and partially in spleen, but not in other tissues (blood, bone marrow, lung, kidney). In conclusion, while drug carrier systems target distinct myeloid cell populations in diseased and healthy livers, hepatic fibrosis profoundly affects their targeting efficiency, supporting the need to adapt nanomedicine-based approaches in chronic liver disease.

Original languageEnglish
Pages (from-to)49-60
Number of pages12
JournalBiomaterials
Volume206
Early online date22 Mar 2019
DOIs
Publication statusPublished - 1 Jun 2019

Fingerprint

Macrophages
Drug Delivery Systems
Liver Cirrhosis
Liver
Myeloid Cells
Fibrosis
Microbubbles
Liposomes
Liver Diseases
Polymers
Chronic Disease
Nanomedicine
Inflammation
Cyanoacrylates
Medical nanotechnology
Whole Body Imaging
Drug Carriers
Flow cytometry
Fluorescent Antibody Technique
Hepatocytes

Keywords

  • Liposomes
  • Liver fibrosis
  • Macrophages
  • Microbubbles
  • Nanomedicine
  • Polymers
  • Targeted delivery

Cite this

Ergen, C., Niemietz, P. M., Heymann, F., Baues, M., Gremse, F., Pola, R., ... Tacke, F. (2019). Liver fibrosis affects the targeting properties of drug delivery systems to macrophage subsets in vivo. Biomaterials, 206, 49-60. https://doi.org/10.1016/j.biomaterials.2019.03.025
Ergen, Can ; Niemietz, Patricia Maria ; Heymann, Felix ; Baues, Maike ; Gremse, Felix ; Pola, Robert ; van Bloois, Louis ; Storm, Gert ; Kiessling, Fabian ; Trautwein, Christian ; Luedde, Tom ; Lammers, Twan ; Tacke, Frank. / Liver fibrosis affects the targeting properties of drug delivery systems to macrophage subsets in vivo. In: Biomaterials. 2019 ; Vol. 206. pp. 49-60.
@article{c30b79402da94d4ea98335ee44817a83,
title = "Liver fibrosis affects the targeting properties of drug delivery systems to macrophage subsets in vivo",
abstract = "Myeloid immune cells promote inflammation and fibrosis in chronic liver diseases. Drug delivery systems, such as polymers, liposomes and microbubbles, efficiently target myeloid cells in healthy liver, but their targeting properties in hepatic fibrosis remain elusive. We therefore studied the biodistribution of three intravenously injected carrier material, i.e. 10 nm poly(N-(2-hydroxypropyl)methacrylamide) polymers, 100 nm PEGylated liposomes and 2000 nm poly(butyl cyanoacrylate) microbubbles, in two fibrosis models in immunocompetent mice. While whole-body imaging confirmed preferential hepatic uptake even after induction of liver fibrosis, flow cytometry and immunofluorescence analysis revealed markedly decreased carrier uptake by liver macrophage subsets in fibrosis, particularly for microbubbles and polymers. Importantly, carrier uptake co-localized with immune infiltrates in fibrotic livers, corroborating the intrinsic ability of the carriers to target myeloid cells in areas of inflammation. Of the tested carrier systems liposomes had the highest uptake efficiency among hepatic myeloid cells, but the lowest specificity for cellular subsets. Hepatic fibrosis affected carrier uptake in liver and partially in spleen, but not in other tissues (blood, bone marrow, lung, kidney). In conclusion, while drug carrier systems target distinct myeloid cell populations in diseased and healthy livers, hepatic fibrosis profoundly affects their targeting efficiency, supporting the need to adapt nanomedicine-based approaches in chronic liver disease.",
keywords = "Liposomes, Liver fibrosis, Macrophages, Microbubbles, Nanomedicine, Polymers, Targeted delivery",
author = "Can Ergen and Niemietz, {Patricia Maria} and Felix Heymann and Maike Baues and Felix Gremse and Robert Pola and {van Bloois}, Louis and Gert Storm and Fabian Kiessling and Christian Trautwein and Tom Luedde and Twan Lammers and Frank Tacke",
year = "2019",
month = "6",
day = "1",
doi = "10.1016/j.biomaterials.2019.03.025",
language = "English",
volume = "206",
pages = "49--60",
journal = "Biomaterials",
issn = "0142-9612",
publisher = "Elsevier",

}

Ergen, C, Niemietz, PM, Heymann, F, Baues, M, Gremse, F, Pola, R, van Bloois, L, Storm, G, Kiessling, F, Trautwein, C, Luedde, T, Lammers, T & Tacke, F 2019, 'Liver fibrosis affects the targeting properties of drug delivery systems to macrophage subsets in vivo' Biomaterials, vol. 206, pp. 49-60. https://doi.org/10.1016/j.biomaterials.2019.03.025

Liver fibrosis affects the targeting properties of drug delivery systems to macrophage subsets in vivo. / Ergen, Can; Niemietz, Patricia Maria; Heymann, Felix; Baues, Maike; Gremse, Felix; Pola, Robert; van Bloois, Louis; Storm, Gert; Kiessling, Fabian; Trautwein, Christian; Luedde, Tom; Lammers, Twan; Tacke, Frank (Corresponding Author).

In: Biomaterials, Vol. 206, 01.06.2019, p. 49-60.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Liver fibrosis affects the targeting properties of drug delivery systems to macrophage subsets in vivo

AU - Ergen, Can

AU - Niemietz, Patricia Maria

AU - Heymann, Felix

AU - Baues, Maike

AU - Gremse, Felix

AU - Pola, Robert

AU - van Bloois, Louis

AU - Storm, Gert

AU - Kiessling, Fabian

AU - Trautwein, Christian

AU - Luedde, Tom

AU - Lammers, Twan

AU - Tacke, Frank

PY - 2019/6/1

Y1 - 2019/6/1

N2 - Myeloid immune cells promote inflammation and fibrosis in chronic liver diseases. Drug delivery systems, such as polymers, liposomes and microbubbles, efficiently target myeloid cells in healthy liver, but their targeting properties in hepatic fibrosis remain elusive. We therefore studied the biodistribution of three intravenously injected carrier material, i.e. 10 nm poly(N-(2-hydroxypropyl)methacrylamide) polymers, 100 nm PEGylated liposomes and 2000 nm poly(butyl cyanoacrylate) microbubbles, in two fibrosis models in immunocompetent mice. While whole-body imaging confirmed preferential hepatic uptake even after induction of liver fibrosis, flow cytometry and immunofluorescence analysis revealed markedly decreased carrier uptake by liver macrophage subsets in fibrosis, particularly for microbubbles and polymers. Importantly, carrier uptake co-localized with immune infiltrates in fibrotic livers, corroborating the intrinsic ability of the carriers to target myeloid cells in areas of inflammation. Of the tested carrier systems liposomes had the highest uptake efficiency among hepatic myeloid cells, but the lowest specificity for cellular subsets. Hepatic fibrosis affected carrier uptake in liver and partially in spleen, but not in other tissues (blood, bone marrow, lung, kidney). In conclusion, while drug carrier systems target distinct myeloid cell populations in diseased and healthy livers, hepatic fibrosis profoundly affects their targeting efficiency, supporting the need to adapt nanomedicine-based approaches in chronic liver disease.

AB - Myeloid immune cells promote inflammation and fibrosis in chronic liver diseases. Drug delivery systems, such as polymers, liposomes and microbubbles, efficiently target myeloid cells in healthy liver, but their targeting properties in hepatic fibrosis remain elusive. We therefore studied the biodistribution of three intravenously injected carrier material, i.e. 10 nm poly(N-(2-hydroxypropyl)methacrylamide) polymers, 100 nm PEGylated liposomes and 2000 nm poly(butyl cyanoacrylate) microbubbles, in two fibrosis models in immunocompetent mice. While whole-body imaging confirmed preferential hepatic uptake even after induction of liver fibrosis, flow cytometry and immunofluorescence analysis revealed markedly decreased carrier uptake by liver macrophage subsets in fibrosis, particularly for microbubbles and polymers. Importantly, carrier uptake co-localized with immune infiltrates in fibrotic livers, corroborating the intrinsic ability of the carriers to target myeloid cells in areas of inflammation. Of the tested carrier systems liposomes had the highest uptake efficiency among hepatic myeloid cells, but the lowest specificity for cellular subsets. Hepatic fibrosis affected carrier uptake in liver and partially in spleen, but not in other tissues (blood, bone marrow, lung, kidney). In conclusion, while drug carrier systems target distinct myeloid cell populations in diseased and healthy livers, hepatic fibrosis profoundly affects their targeting efficiency, supporting the need to adapt nanomedicine-based approaches in chronic liver disease.

KW - Liposomes

KW - Liver fibrosis

KW - Macrophages

KW - Microbubbles

KW - Nanomedicine

KW - Polymers

KW - Targeted delivery

UR - http://www.scopus.com/inward/record.url?scp=85063583621&partnerID=8YFLogxK

U2 - 10.1016/j.biomaterials.2019.03.025

DO - 10.1016/j.biomaterials.2019.03.025

M3 - Article

VL - 206

SP - 49

EP - 60

JO - Biomaterials

JF - Biomaterials

SN - 0142-9612

ER -