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Hybrid nanoparticles improve targeting to inflammatory macrophages through phagocytic signals
Macrophages are innate immune cells with great phenotypic plasticity, which allows them to regulate an array of physiological processes such as host defense, tissue repair, and lipid/lipoprotein metabolism. In this proof-of-principle study, we report that macrophages of the M1 inflammatory phenotype...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4874242/ https://www.ncbi.nlm.nih.gov/pubmed/26386437 http://dx.doi.org/10.1016/j.jconrel.2015.09.027 |
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author | Bagalkot, Vaishali Badgeley, Marcus A. Kampfrath, Thomas Deiuliis, Jeffrey A. Rajagopalan, Sanjay Maiseyeu, Andrei |
author_facet | Bagalkot, Vaishali Badgeley, Marcus A. Kampfrath, Thomas Deiuliis, Jeffrey A. Rajagopalan, Sanjay Maiseyeu, Andrei |
author_sort | Bagalkot, Vaishali |
collection | PubMed |
description | Macrophages are innate immune cells with great phenotypic plasticity, which allows them to regulate an array of physiological processes such as host defense, tissue repair, and lipid/lipoprotein metabolism. In this proof-of-principle study, we report that macrophages of the M1 inflammatory phenotype can be selectively targeted by model hybrid lipid–latex (LiLa) nanoparticles bearing phagocytic signals. We demonstrate a simple and robust route to fabricate nanoparticles and then show their efficacy through imaging and drug delivery in inflammatory disease models of atherosclerosis and obesity. Self-assembled LiLa nanoparticles can be modified with a variety of hydrophobic entities such as drug cargos, signaling lipids, and imaging reporters resulting in sub-100 nm nano-particles with low polydispersities. The optimized theranostic LiLa formulation with gadolinium, fluorescein and “eat-me” phagocytic signals (Gd-FITC-LiLa) a) demonstrates high relaxivity that improves magnetic resonance imaging (MRI) sensitivity, b) encapsulates hydrophobic drugs at up to 60% by weight, and c) selectively targets inflammatory M1 macrophages concomitant with controlled release of the payload of anti-inflammatory drug. The mechanism and kinetics of the payload discharge appeared to be phospholipase A2 activity-dependent, as determined by means of intracellular Förster resonance energy transfer (FRET). In vivo, LiLa targets M1 macrophages in a mouse model of atherosclerosis, allowing noninvasive imaging of atherosclerotic plaque by MRI. In the context of obesity, LiLa particles were selectively deposited to M1 macrophages within inflamed adipose tissue, as demonstrated by single-photon intravital imaging in mice. Collectively, our results suggest that phagocytic signals can preferentially target inflammatory macrophages in experimental models of atherosclerosis and obesity, thus opening the possibility of future clinical applications that diagnose/treat these conditions. Tunable LiLa nanoparticles reported here can serve as a model theranostic platform with application in various types of imaging of the diseases such as cardiovascular disorders, obesity, and cancer where macrophages play a pathogenic role. |
format | Online Article Text |
id | pubmed-4874242 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
record_format | MEDLINE/PubMed |
spelling | pubmed-48742422016-05-20 Hybrid nanoparticles improve targeting to inflammatory macrophages through phagocytic signals Bagalkot, Vaishali Badgeley, Marcus A. Kampfrath, Thomas Deiuliis, Jeffrey A. Rajagopalan, Sanjay Maiseyeu, Andrei J Control Release Article Macrophages are innate immune cells with great phenotypic plasticity, which allows them to regulate an array of physiological processes such as host defense, tissue repair, and lipid/lipoprotein metabolism. In this proof-of-principle study, we report that macrophages of the M1 inflammatory phenotype can be selectively targeted by model hybrid lipid–latex (LiLa) nanoparticles bearing phagocytic signals. We demonstrate a simple and robust route to fabricate nanoparticles and then show their efficacy through imaging and drug delivery in inflammatory disease models of atherosclerosis and obesity. Self-assembled LiLa nanoparticles can be modified with a variety of hydrophobic entities such as drug cargos, signaling lipids, and imaging reporters resulting in sub-100 nm nano-particles with low polydispersities. The optimized theranostic LiLa formulation with gadolinium, fluorescein and “eat-me” phagocytic signals (Gd-FITC-LiLa) a) demonstrates high relaxivity that improves magnetic resonance imaging (MRI) sensitivity, b) encapsulates hydrophobic drugs at up to 60% by weight, and c) selectively targets inflammatory M1 macrophages concomitant with controlled release of the payload of anti-inflammatory drug. The mechanism and kinetics of the payload discharge appeared to be phospholipase A2 activity-dependent, as determined by means of intracellular Förster resonance energy transfer (FRET). In vivo, LiLa targets M1 macrophages in a mouse model of atherosclerosis, allowing noninvasive imaging of atherosclerotic plaque by MRI. In the context of obesity, LiLa particles were selectively deposited to M1 macrophages within inflamed adipose tissue, as demonstrated by single-photon intravital imaging in mice. Collectively, our results suggest that phagocytic signals can preferentially target inflammatory macrophages in experimental models of atherosclerosis and obesity, thus opening the possibility of future clinical applications that diagnose/treat these conditions. Tunable LiLa nanoparticles reported here can serve as a model theranostic platform with application in various types of imaging of the diseases such as cardiovascular disorders, obesity, and cancer where macrophages play a pathogenic role. 2015-09-18 2015-11-10 /pmc/articles/PMC4874242/ /pubmed/26386437 http://dx.doi.org/10.1016/j.jconrel.2015.09.027 Text en This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Article Bagalkot, Vaishali Badgeley, Marcus A. Kampfrath, Thomas Deiuliis, Jeffrey A. Rajagopalan, Sanjay Maiseyeu, Andrei Hybrid nanoparticles improve targeting to inflammatory macrophages through phagocytic signals |
title | Hybrid nanoparticles improve targeting to inflammatory macrophages through phagocytic signals |
title_full | Hybrid nanoparticles improve targeting to inflammatory macrophages through phagocytic signals |
title_fullStr | Hybrid nanoparticles improve targeting to inflammatory macrophages through phagocytic signals |
title_full_unstemmed | Hybrid nanoparticles improve targeting to inflammatory macrophages through phagocytic signals |
title_short | Hybrid nanoparticles improve targeting to inflammatory macrophages through phagocytic signals |
title_sort | hybrid nanoparticles improve targeting to inflammatory macrophages through phagocytic signals |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4874242/ https://www.ncbi.nlm.nih.gov/pubmed/26386437 http://dx.doi.org/10.1016/j.jconrel.2015.09.027 |
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