Cell specific expression of uptake transporters - a potential approach for cardiovascular drug delivery devices
JournalArticle (Originalarbeit in einer wissenschaftlichen Zeitschrift)
 
ID 2379231
Author(s) Meyer Zu Schwabedissen, Henriette E; Begunk, Robert; Hussner, Janine; Juhnke, B Ole; Gliesche, Daniel; Böttcher, Kerstin; Sternberg, Katrin; Schmitz, Klaus-Peter; Kroemer, Heyo K
Author(s) at UniBasel Meyer zu Schwabedissen, Henriette
Hussner, Janine
Gliesche, Daniel
Year 2014
Title Cell specific expression of uptake transporters - a potential approach for cardiovascular drug delivery devices
Journal Molecular pharmaceutics
Volume 11
Number 3
Pages / Article-Number 665-72
Abstract

Enhanced proliferation of human coronary artery smooth muscle cells (HCASMCs) and thereby formation of neointima is one of the factors contributing to failure of coronary stents. Even if the use of drug eluting stents and thereby the local delivery of cytotoxic compounds has significantly improved clinical outcome, unselective cytotoxicity is assumed to hamper clinical success. Novel pharmacological approaches are required to enhance cellular selectivity of locally delivered drugs. Cell specific overexpression of a drug transporter could be used to enhance cellular accumulation and therefore cell specificity. In the herein reported study we tested the possibility of cell specific transporter expression to enhance drug effects in HCASMCs. We generated adenoviral constructs to overexpress the organic cation transporter 1 (OCT1) under control of the promoter of SM22α, which had been previously reported as muscle cell-specific gene. First the activity of the SM22α-promoter was assessed in various cell types supporting the notion of muscle cell-specificity. Subsequently, the activity of the transporter was compared in infected human coronary artery endothelial cells (HCAECs) and HCASMCs revealing enhanced accumulation of substrate drugs in HCASMCs in presence of the SM22α-promoter. Testing the hypothesis that this kind of targeting might serve as a mechanism for cell-specific drug effects we investigated the impact on paclitaxel treatment in HCASMC and HCAECs, showing significantly increased anti-proliferative activity of this substrate drug on muscle cells. Taken together, our findings suggest that cell-specific expression of transport proteins serves as mechanism governing the uptake of cytotoxic compounds for a selective impact on targeted cells.

Publisher American Chemical Society
ISSN/ISBN 1543-8384
edoc-URL http://edoc.unibas.ch/dok/A6308343
Full Text on edoc No
Digital Object Identifier DOI 10.1021/mp400245g
PubMed ID http://www.ncbi.nlm.nih.gov/pubmed/24495124
ISI-Number WOS:000332348600002
Document type (ISI) Journal Article
 
   

MCSS v5.8 PRO. 0.323 sec, queries - 0.000 sec ©Universität Basel  |  Impressum   |    
04/12/2022