Anchoring of self-assembled plasmid DNA/ anti-DNA antibody/cationic lipid micelles on bisphosphonate-modified stent for cardiovascular gene delivery

Guilei Ma,1,# Yong Wang,1,# Ilia Fishbein,2 Mei Yu,1 Linhua Zhang,1 Ivan S Alferiev,2 Jing Yang,1 Cunxian Song,1 Robert J Levy2 1Institute of Biomedical Engineering, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, People&#39;s Republic of China; 2Children&a...

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Autores principales:	Ma G, Wang Y, Fishbein I, Yu M, Zhang L, Alferiev IS, Yang J, Song C, Levy RJ
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2013
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/043efd16a3b549b185311be80311d21a
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spelling	oai:doaj.org-article:043efd16a3b549b185311be80311d21a2021-12-02T01:16:06ZAnchoring of self-assembled plasmid DNA/ anti-DNA antibody/cationic lipid micelles on bisphosphonate-modified stent for cardiovascular gene delivery1176-91141178-2013https://doaj.org/article/043efd16a3b549b185311be80311d21a2013-03-01T00:00:00Zhttp://www.dovepress.com/anchoring-of-self-assembled-plasmid-dna-anti-dna-antibodycationic-lipi-a12434https://doaj.org/toc/1176-9114https://doaj.org/toc/1178-2013Guilei Ma,1,# Yong Wang,1,# Ilia Fishbein,2 Mei Yu,1 Linhua Zhang,1 Ivan S Alferiev,2 Jing Yang,1 Cunxian Song,1 Robert J Levy2 1Institute of Biomedical Engineering, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, People&#39;s Republic of China; 2Children&#39;s Hospital of Philadelphia, Abramson Research Building, Philadelphia, PA, USA #These authors contributed equally to this work Purpose: To investigate the anchoring of plasmid DNA/anti-DNA antibody/cationic lipid tri-complex (DAC micelles) onto bisphosphonate-modified 316 L coronary stents for cardiovascular site-specific gene delivery. Methods: Stents were first modified with polyallylamine bisphosphonate (PAA-BP), thereby enabling the retention of a PAA-BP molecular monolayer that permits the anchoring (via vector-binding molecules) of DAC micelles. DAC micelles were then chemically linked onto the PAA-BP-modified stents by using N-succinimidyl-3-(2-pyridyldithiol)-propionate (SPDP) as a crosslinker. Rhodamine-labeled DNA was used to assess the anchoring of DAC micelles, and radioactive-labeled antibody was used to evaluate binding capacity and stability. DAC micelles (encoding green fluorescent protein) were tethered onto the PAA-BP-modified stents, which were assessed in cell culture. The presence of a PAA-BP molecular monolayer on the steel surface was confirmed by X-ray photoelectron spectroscopy and atomic force microscope analysis. Results: The anchoring of DAC micelles was generally uniform and devoid of large-scale patches of defects. Isotopic quantification confirmed that the amount of antibody chemically linked on the stents was 17-fold higher than that of the physical adsorbed control stents and its retention time was also significantly longer. In cell culture, numerous green fluorescent protein-positive cells were found on the PAA-BP modified stents, which demonstrated high localization and efficiency of gene delivery. Conclusion: The DAC micelle-immobilized PAA-BP-modified stents were successful as a gene delivery system. Gene delivery using DAC micelle-tethered stent-based PAA-BP functionalization should be suitable for a wide array of single or multiple therapeutic gene strategies, and could be used on cardiovascular metallic implants for achieving efficient gene therapy. Keywords: stent, polyallylamine bisphosphonate, plasmid DNA, micelles, gene deliveryMa GWang YFishbein IYu MZhang LAlferiev ISYang JSong CLevy RJDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2013, Iss default, Pp 1029-1035 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Ma G Wang Y Fishbein I Yu M Zhang L Alferiev IS Yang J Song C Levy RJ Anchoring of self-assembled plasmid DNA/ anti-DNA antibody/cationic lipid micelles on bisphosphonate-modified stent for cardiovascular gene delivery
description	Guilei Ma,1,# Yong Wang,1,# Ilia Fishbein,2 Mei Yu,1 Linhua Zhang,1 Ivan S Alferiev,2 Jing Yang,1 Cunxian Song,1 Robert J Levy2 1Institute of Biomedical Engineering, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, People&#39;s Republic of China; 2Children&#39;s Hospital of Philadelphia, Abramson Research Building, Philadelphia, PA, USA #These authors contributed equally to this work Purpose: To investigate the anchoring of plasmid DNA/anti-DNA antibody/cationic lipid tri-complex (DAC micelles) onto bisphosphonate-modified 316 L coronary stents for cardiovascular site-specific gene delivery. Methods: Stents were first modified with polyallylamine bisphosphonate (PAA-BP), thereby enabling the retention of a PAA-BP molecular monolayer that permits the anchoring (via vector-binding molecules) of DAC micelles. DAC micelles were then chemically linked onto the PAA-BP-modified stents by using N-succinimidyl-3-(2-pyridyldithiol)-propionate (SPDP) as a crosslinker. Rhodamine-labeled DNA was used to assess the anchoring of DAC micelles, and radioactive-labeled antibody was used to evaluate binding capacity and stability. DAC micelles (encoding green fluorescent protein) were tethered onto the PAA-BP-modified stents, which were assessed in cell culture. The presence of a PAA-BP molecular monolayer on the steel surface was confirmed by X-ray photoelectron spectroscopy and atomic force microscope analysis. Results: The anchoring of DAC micelles was generally uniform and devoid of large-scale patches of defects. Isotopic quantification confirmed that the amount of antibody chemically linked on the stents was 17-fold higher than that of the physical adsorbed control stents and its retention time was also significantly longer. In cell culture, numerous green fluorescent protein-positive cells were found on the PAA-BP modified stents, which demonstrated high localization and efficiency of gene delivery. Conclusion: The DAC micelle-immobilized PAA-BP-modified stents were successful as a gene delivery system. Gene delivery using DAC micelle-tethered stent-based PAA-BP functionalization should be suitable for a wide array of single or multiple therapeutic gene strategies, and could be used on cardiovascular metallic implants for achieving efficient gene therapy. Keywords: stent, polyallylamine bisphosphonate, plasmid DNA, micelles, gene delivery
format	article
author	Ma G Wang Y Fishbein I Yu M Zhang L Alferiev IS Yang J Song C Levy RJ
author_facet	Ma G Wang Y Fishbein I Yu M Zhang L Alferiev IS Yang J Song C Levy RJ
author_sort	Ma G
title	Anchoring of self-assembled plasmid DNA/ anti-DNA antibody/cationic lipid micelles on bisphosphonate-modified stent for cardiovascular gene delivery
title_short	Anchoring of self-assembled plasmid DNA/ anti-DNA antibody/cationic lipid micelles on bisphosphonate-modified stent for cardiovascular gene delivery
title_full	Anchoring of self-assembled plasmid DNA/ anti-DNA antibody/cationic lipid micelles on bisphosphonate-modified stent for cardiovascular gene delivery
title_fullStr	Anchoring of self-assembled plasmid DNA/ anti-DNA antibody/cationic lipid micelles on bisphosphonate-modified stent for cardiovascular gene delivery
title_full_unstemmed	Anchoring of self-assembled plasmid DNA/ anti-DNA antibody/cationic lipid micelles on bisphosphonate-modified stent for cardiovascular gene delivery
title_sort	anchoring of self-assembled plasmid dna/ anti-dna antibody/cationic lipid micelles on bisphosphonate-modified stent for cardiovascular gene delivery
publisher	Dove Medical Press
publishDate	2013
url	https://doaj.org/article/043efd16a3b549b185311be80311d21a
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Anchoring of self-assembled plasmid DNA/ anti-DNA antibody/cationic lipid micelles on bisphosphonate-modified stent for cardiovascular gene delivery

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