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

G.L. Ma, Y. Wang, I. Fishbein, M. Yu, L.H. Zhang, I.S. Alferiev, J. Yang, C.X. Song, R.J. Levy
Chinese Academy of Medical Sciences and Peking Union Medical College, CN

Keywords: stent, polyallylamine bisphosphonate, plasmid DNA, micelles, gene delivery


In the present studies, we intended to explore new applications of plasmid DNA/anti-DNA antibody/cationic lipid tri-complex (DAC micelles) in gene delivery and further investigate the binding stability and the controlled delivery behavior of DAC micelles bound on polyallylamine bisphosphonate (PAA-BP)-modified stent surface. Stents were first modified with PAA-BP, thereby enabling the retention of a PAA-BP molecular monolayer that permits the anchoring (via vector-binding molecules) of DAC micelles. Then DAC micelles were chemically linked onto PAA-BP-modified stent by using N-succinimidyl-3-(2-pyridyldithiol)-propionate (SPDP) as cross-linker. It is concluded that the success of using DAC micelles-immobilized PAA-BP-modified stent as a gene delivery system. Gene delivery using DAC micelles-tethered stents-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.