Abstract
Liver diseases characteristically progress from chronic inflammation to aberrant wound-healing with excessive scarring, termed fibrosis, and eventually to liver cancer. Since hepatic macrophages are critical regulators of these inflammatory processes, it appears promising to target these cells with novel nanomedicine-based therapeutics. Nanomedicine bears a large potential for the design of novel drugs by site-specific delivery and controlled release. Nanotheranostics allow for additional in vivo tracing of the therapeutics. Therapeutic nanoparticles are, in most cases, composed of biodegradable compounds such as phospholipids, which are an essential part of biological membranes. Nanodrugs may interact with soluble parts of the immune system (humoral immunity), specifically with components that help immune cells in pathogen recognition such as antibodies or complement factors. Macrophages are a heterogeneous cell type being composed of pro- or anti-inflammatory subtypes that can either heal or worsen inflammatory diseases as well as combat or support cancer growth. Due to their inherent capability of foreign material uptake, macrophages are relatively easy to target, but may also hinder particles from reaching other target cells. A variety of receptors attractive for targeting was found to be useful in more specific strategies for selectively modulating macrophages to overcome effects on other cell types. In this chapter, current strategies to target macrophages in liver diseases and cancer are reviewed.
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References
Lammers T, Aime S, Hennink WE et al (2011) Theranostic nanomedicine. Acc Chem Res 44(10):1029–1038
Petros RA, DeSimone JM (2010) Strategies in the design of nanoparticles for therapeutic applications. Nat Rev Drug Discov 9(8):615–627
Bartneck M, Keul HA, Zwadlo-Klarwasser G et al (2010) Phagocytosis independent extracellular nanoparticle clearance by human immune cells. Nano Lett 10(1):59–63
Bartneck M, Warzecha KT, Tacke F (2014) Therapeutic targeting of liver inflammation and fibrosis by nanomedicine. Hepatobiliary Surg Nutr 3(6):364–376
Abu Lila AS, Ichihara M, Shimizu T et al (2013) Ex-vivo/in-vitro anti-polyethylene glycol (PEG) immunoglobulin M production from murine splenic B cells stimulated by PEGylated liposome. Biol Pharm Bull 36(11):1842–1848
Pawlotsky JM, Feld JJ, Zeuzem S et al (2015) From non-A, non-B hepatitis to hepatitis C virus cure. J Hepatol 62(1 Suppl):S87–S99
Bartneck M, Keul HA, Singh S et al (2010) Rapid uptake of gold nanorods by primary human blood phagocytes and immunomodulatory effects of surface chemistry. ACS Nano 4(6):3073–3086
Moghimi SM, Szebeni J (2003) Stealth liposomes and long circulating nanoparticles: critical issues in pharmacokinetics, opsonization and protein-binding properties. Prog Lipid Res 42(6):463–478
Murray PJ, Allen JE, Biswas SK et al (2014) Macrophage activation and polarization: nomenclature and experimental guidelines. Immunity 41(1):14–20
Martinez FO, Sica A, Mantovani A et al (2008) Macrophage activation and polarization. Front Biosci 13:453–461
Tacke HW, Zimmermann F (2014) Macrophage heterogeneity in liver injury and fibrosis. J Hepatol 60(5):1090–1096
Dal-Secco D, Wang J, Zeng Z et al (2015) A dynamic spectrum of monocytes arising from the in situ reprogramming of CCR2+ monocytes at a site of sterile injury. J Exp Med 212(4):447–456
Bartneck M, Ritz T, Keul HA et al (2012) Peptide-functionalized gold nanorods increase liver injury in hepatitis. ACS Nano 6(10):8767–8777
Bartneck M, Peters FM, Warzecha KT et al (2014) Liposomal encapsulation of dexamethasone modulates cytotoxicity, inflammatory cytokine response, and migratory properties of primary human macrophages. Nanomedicine 10(6):1209–1220
Sadauskas E, Wallin H, Stoltenberg M et al (2007) Kupffer cells are central in the removal of nanoparticles from the organism. Part Fibre Toxicol 4:10
Csak T, Ganz M, Pespisa J et al (2011) Fatty acid and endotoxin activate inflammasomes in mouse hepatocytes that release danger signals to stimulate immune cells. Hepatology 54(1):133–144
Karlmark KR, Weiskirchen R, Zimmermann HW et al (2009) Hepatic recruitment of the inflammatory Gr1+ monocyte subset upon liver injury promotes hepatic fibrosis. Hepatology 50(1):261–274
Bataller DA, Brenner R (2005) Liver fibrosis. J Clin Invest 115(2):209–218
Vucur M, Roderburg C, Bettermann K et al (2010) Mouse models of hepatocarcinogenesis: what can we learn for the prevention of human hepatocellular carcinoma? Oncotarget 1(5):373–378
Ehling J, Tacke F (2016) Role of chemokine pathways in hepatobiliary cancer. Cancer Lett 379(2):173–183
Bartneck M, Fech V, Ehling J et al (2015) Histidine-rich glycoprotein promotes macrophage activation and inflammation in chronic liver disease. Hepatology 63(4):1310–1324
Wynn TA, Barron L (2010) Macrophages: master regulators of inflammation and fibrosis. Semin Liver Dis 30(3):245–257
He C, Ryan AJ, Murthy S et al (2013) Accelerated development of pulmonary fibrosis via Cu, Zn-sod-induced alternative activation of macrophages. J Biol Chem 288(28):20745–20757
Meznarich J, Malchodi L, Helterline D et al (2013) Urokinase plasminogen activator induces pro-fibrotic/m2 phenotype in murine cardiac macrophages. PLoS One 8(3), e57837
Tacke C, Trautwein F (2015) Mechanisms of liver fibrosis resolution. J Hepatol 63(4):1038–1039
Mossanen JC, Tacke F (2013) Role of lymphocytes in liver cancer. Oncoimmunology 2(11), e26468
Movahedi K, Laoui D, Gysemans C et al (2010) Different tumor microenvironments contain functionally distinct subsets of macrophages derived from Ly6C(high) monocytes. Cancer Res 70(14):5728–5739
Bartneck M, Scheyda KM, Warzecha KT et al (2015) Fluorescent cell-traceable dexamethasone-loaded liposomes for the treatment of inflammatory liver diseases. Biomaterials 37:367–382
Kai MP, Brighton HE, Fromen CA et al (2016) Tumor presence induces global immune changes and enhances nanoparticle clearance. ACS Nano 10(1):861–70
Muller RH, Maassen S, Weyhers H et al (1996) Phagocytic uptake and cytotoxicity of solid lipid nanoparticles (SLN) sterically stabilized with poloxamine 908 and poloxamer 407. J Drug Target 4(3):161–170
Bilzer M, Roggel AL, Gerbes F (2006) Role of Kupffer cells in host defense and liver disease. Liver Int 26(10):1175–1186
Pan Y, Neuss S, Leifert A et al (2007) Size-dependent cytotoxicity of gold nanoparticles. Small 3(11):1941–1949
Choi HS, Liu W, Misra P et al (2007) Renal clearance of quantum dots. Nat Biotechnol 25(10):1165–1170
Bartneck M, Keul HA, Wambach M et al (2012) Effects of nanoparticle surface coupled peptides, functional endgroups and charge on intracellular distribution and functionality of human primary reticuloendothelial cells. Nanomedicine 8(8):1282–1292
Beljaars L, Molema G, Weert B et al (1999) Albumin modified with mannose 6-phosphate: a potential carrier for selective delivery of antifibrotic drugs to rat and human hepatic stellate cells. Hepatology 29(5):1486–1493
Blykers A, Schoonooghe S, Xavier C et al (2015) PET imaging of macrophage mannose receptor-expressing macrophages in tumor stroma using 18F-radiolabeled camelid single-domain antibody fragments. J Nucl Med 56(8):1265–1271
He C, Yin L, Tang C et al (2013) Multifunctional polymeric nanoparticles for oral delivery of TNF-alpha siRNA to macrophages. Biomaterials 34(11):2843–2854
Melgert BN, Olinga P, Van Der Laan JM et al (2001) Targeting dexamethasone to Kupffer cells: effects on liver inflammation and fibrosis in rats. Hepatology 34(4 Pt 1):719–728
Dresser GK, Spence JD, Bailey DG (2000) Pharmacokinetic-pharmacodynamic consequences and clinical relevance of cytochrome P450 3A4 inhibition. Clin Pharmacokinet 38(1):41–57
Asthana S, Jaiswal AK, Gupta PK et al (2015) Th-1 biased immunomodulation and synergistic antileishmanial activity of stable cationic lipid-polymer hybrid nanoparticle: biodistribution and toxicity assessment of encapsulated amphotericin B. Eur J Pharm Biopharm 89:62–73
Liu JY, Chiang T, Liu CH et al (2015) Delivery of siRNA using CXCR4-targeted nanoparticles modulates tumor microenvironment and achieves a potent antitumor response in liver cancer. Mol Ther 23(11):1772–1782
Kummerer K, Menz J, Schubert T et al (2011) Biodegradability of organic nanoparticles in the aqueous environment. Chemosphere 82(10):1387–1392
Schulte W, Bernhagen R, Bucala J (2013) Cytokines in sepsis: potent immunoregulators and potential therapeutic targets—an updated view. Mediators Inflamm 2013:165974
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Bartneck, M., Tacke, F. (2017). Targeted Modulation of Macrophage Functionality by Nanotheranostics in Inflammatory Liver Disease and Cancer. In: Corradetti, B. (eds) The Immune Response to Implanted Materials and Devices. Springer, Cham. https://doi.org/10.1007/978-3-319-45433-7_11
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DOI: https://doi.org/10.1007/978-3-319-45433-7_11
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