Non-Viral Nanoparticle Delivers Small Interfering RNA to Macrophages In Vitro and In Vivo

Macrophages are increasingly being viewed as therapeutic target for various cancers and many inflammatory diseases. Sequence specific gene reduction by siRNA represents an attractive approach to modulate macrophage function. However, delivery of the therapeutic siRNA into macrophages by non-viral na...

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Main Authors:	Zhang, Mei, Gao, Yunxiang, Caja, Kevin, Zhao, Bocheng, Kim, Julian A.
Format:	Online
Language:	English
Published:	Public Library of Science 2015
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4370462/

id	pubmed-4370462
recordtype	oai_dc
spelling	pubmed-43704622015-04-04 Non-Viral Nanoparticle Delivers Small Interfering RNA to Macrophages In Vitro and In Vivo Zhang, Mei Gao, Yunxiang Caja, Kevin Zhao, Bocheng Kim, Julian A. Research Article Macrophages are increasingly being viewed as therapeutic target for various cancers and many inflammatory diseases. Sequence specific gene reduction by siRNA represents an attractive approach to modulate macrophage function. However, delivery of the therapeutic siRNA into macrophages by non-viral nanoparticles has been a major technical challenge. In this study, we developed a glucan-based siRNA carrier system (BG34-10-Re-I) and demonstrated that the BG34-10-Re-I can effectively assemble siRNA into uniformly distributed nanoparticles of the novel core-shell structure. The BG34-10-Re-I/siRNA nanoparticles effectively reduced gene expression of macrophage migration inhibitory factor (MIF) in primary macrophages at both protein and mRNA level. The nanoparticles also mediated a sustained reduction of MIF within primary macrophages. Moreover, systemic injection of the nanoparticles into the Balb/c mice bearing 4T1 mammary tumors resulted in the MIF reduction in tumor-associated macrophages. Mechanistic studies demonstrated that the glucan-shell and the siRNA-core structure contribute to the effective delivery of MIF siRNA to macrophages both in vitro and in vivo. This study represents the first development of the primary macrophage MIF gene targeted non-viral nanoparticle system for both in vitro and in vivo applications. Public Library of Science 2015-03-23 /pmc/articles/PMC4370462/ /pubmed/25799489 http://dx.doi.org/10.1371/journal.pone.0118472 Text en © 2015 Zhang et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Zhang, Mei Gao, Yunxiang Caja, Kevin Zhao, Bocheng Kim, Julian A.
spellingShingle	Zhang, Mei Gao, Yunxiang Caja, Kevin Zhao, Bocheng Kim, Julian A. Non-Viral Nanoparticle Delivers Small Interfering RNA to Macrophages In Vitro and In Vivo
author_facet	Zhang, Mei Gao, Yunxiang Caja, Kevin Zhao, Bocheng Kim, Julian A.
author_sort	Zhang, Mei
title	Non-Viral Nanoparticle Delivers Small Interfering RNA to Macrophages In Vitro and In Vivo
title_short	Non-Viral Nanoparticle Delivers Small Interfering RNA to Macrophages In Vitro and In Vivo
title_full	Non-Viral Nanoparticle Delivers Small Interfering RNA to Macrophages In Vitro and In Vivo
title_fullStr	Non-Viral Nanoparticle Delivers Small Interfering RNA to Macrophages In Vitro and In Vivo
title_full_unstemmed	Non-Viral Nanoparticle Delivers Small Interfering RNA to Macrophages In Vitro and In Vivo
title_sort	non-viral nanoparticle delivers small interfering rna to macrophages in vitro and in vivo
description	Macrophages are increasingly being viewed as therapeutic target for various cancers and many inflammatory diseases. Sequence specific gene reduction by siRNA represents an attractive approach to modulate macrophage function. However, delivery of the therapeutic siRNA into macrophages by non-viral nanoparticles has been a major technical challenge. In this study, we developed a glucan-based siRNA carrier system (BG34-10-Re-I) and demonstrated that the BG34-10-Re-I can effectively assemble siRNA into uniformly distributed nanoparticles of the novel core-shell structure. The BG34-10-Re-I/siRNA nanoparticles effectively reduced gene expression of macrophage migration inhibitory factor (MIF) in primary macrophages at both protein and mRNA level. The nanoparticles also mediated a sustained reduction of MIF within primary macrophages. Moreover, systemic injection of the nanoparticles into the Balb/c mice bearing 4T1 mammary tumors resulted in the MIF reduction in tumor-associated macrophages. Mechanistic studies demonstrated that the glucan-shell and the siRNA-core structure contribute to the effective delivery of MIF siRNA to macrophages both in vitro and in vivo. This study represents the first development of the primary macrophage MIF gene targeted non-viral nanoparticle system for both in vitro and in vivo applications.
publisher	Public Library of Science
publishDate	2015
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4370462/
_version_	1613202327068475392

Non-Viral Nanoparticle Delivers Small Interfering RNA to Macrophages In Vitro and In Vivo

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