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.
journal_name
Biomaterialsjournal_title
Biomaterialsauthors
Sellner S,Kocabey S,Zhang T,Nekolla K,Hutten S,Krombach F,Liedl T,Rehberg Mdoi
10.1016/j.biomaterials.2017.04.031subject
Has Abstractpub_date
2017-07-01 00:00:00pages
78-90eissn
0142-9612issn
1878-5905pii
S0142-9612(17)30266-1journal_volume
134pub_type
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