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Dexamethasone-conjugated DNA nanotubes as anti-inflammatory agents in vivo.
- Source :
-
Biomaterials [Biomaterials] 2017 Jul; Vol. 134, pp. 78-90. Date of Electronic Publication: 2017 Apr 17. - Publication Year :
- 2017
-
Abstract
- The biopolymer DNA allows to create nanoscale, biocompatible structures, which can be designed in a target-specific and stimuli-responsive manner. DNA carrier systems with these characteristics hold a great potential for nanomedical applications, such as for the treatment of inflammatory diseases. Here we used a DNA-based drug carrier system for the pH-dependent delivery of the glucocorticoid dexamethasone into macrophages, a cell type with a key role in the regulation of inflammation. Dexamethasone (Dex) nanotubes were internalized within minutes by MH-S macrophages in vitro and by tissue resident macrophages in the mouse cremaster muscle in vivo and localized in their endosomes. Treatment with Dex nanotubes in vitro significantly reduced the LPS-induced TNF secretion by macrophages, as compared to equivalent amounts of free dexamethasone without affecting cell viability. Microinjection of Dex nanotubes into postischemic muscle tissue of anesthetized mice resulted in a marked reduction of ischemia-reperfusion-elicited leukocyte transmigration and diminished vascular expression of the endothelial adhesion molecules VCAM-1 and ICAM-1. Taken together, our results demonstrate that DNA nanotubes can be used as a platform for the targeted delivery of glucocorticoids and could thus foster the development of nanomedical therapeutics with reduced off-target effects.<br /> (Copyright © 2017 Elsevier Ltd. All rights reserved.)
- Subjects :
- Animals
Anti-Inflammatory Agents chemistry
Anti-Inflammatory Agents therapeutic use
Dexamethasone therapeutic use
Immunohistochemistry
Inflammation drug therapy
Macrophages drug effects
Macrophages metabolism
Male
Mice
Mice, Inbred C57BL
Microscopy, Electron, Transmission
Nanotechnology methods
Nanotubes ultrastructure
Tumor Necrosis Factor-alpha metabolism
DNA chemistry
Dexamethasone chemistry
Nanotubes chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 1878-5905
- Volume :
- 134
- Database :
- MEDLINE
- Journal :
- Biomaterials
- Publication Type :
- Academic Journal
- Accession number :
- 28458030
- Full Text :
- https://doi.org/10.1016/j.biomaterials.2017.04.031