Enhanced Gene Expression Promoted by Hybrid Magnetic/Cationic Block Copolymer Micelles

• DOI: 10.1021/la501402q
• Publication Date: 2014-06-19T15:16:47Z
• Authors: E. Haladjova; S. Rangelov; Ch. B. Tsvetanov; V. Posheva; E. Peycheva; V. Maximova; D. Momekova; G. Mountrichas; S. Pispas; A. Bakandritsos
• Keywords: 0301 basic medicine; Genetic Vectors; Green Fluorescent Proteins; Gene Expression; DNA; Transfection; Cell Line; 03 medical and health sciences; Magnetic Fields; Salmon; Materials Testing; Animals; Humans; Nanoparticles; Polystyrenes; Polyvinyls; Micelles

We report on novel gene delivery vector systems based on hybrid polymer-magnetic micelles. The hybrid micelles were prepared by codissolution of hydrophobically surface modified iron oxide and amphiphilic polystyrene-b-poly(quaternized 2-vinylpyridine) block copolymer (PS-b-P2QVP) in organic solvent. After extensive dialysis against water, micelles with positively charged hydrophilic corona of PQVP and hydrophobic PS core were prepared, in which magnetic nanoparticles were randomly distributed. The hybrid micelles were used to form complexes with linear (salmon sperm, 2000 bp, corresponding to M(w) of 1.32 × 10(6) Da) and plasmid (pEGFP-N1, 4730 bp, corresponding to M(w) of 3.12 × 10(6) Da) DNA. The resulting magnetopolyplexes of phosphate:amine (P/N) ratios in the 0.05-20 range were characterized by light scattering, ζ-potential measurements, and transmission electron microscopy as well as cytotoxicity and gel retardation assays. The investigated systems displayed a narrow size distribution, particle dimensions below 360 nm, whereas their ζ-potential values varied from positive to negative depending of the P/N ratio. The resulting vector nanosystems exhibited low toxicity. They were able to introduce pEGFP-N1 molecules into the cells. The application of a magnetic field markedly boosted the transgene expression efficiency of the magnetopolyplexes, which was even superior to those of commercial transfectants such as Lipofectamine and dendritic polyethylenimine.