Targeting of the β2-adrenoceptor increases nonviral gene delivery to pulmonary epithelial cells in vitro and lungs in vivo
2009
Abstract Coupling of targeting ligands to polyethylenimine (PEI) has been previously used to improve transfection efficiency of PEI gene vectors. Here, we show that the β 2 -adrenoceptor (β 2 -AR) agonist, clenbuterol (Clen), can be used to improve gene transfer efficiency of PEI gene vectors on alveolar epithelial cells in vitro and in the lungs of mice in vivo . Clenbuterol conjugated to fluorescein-labeled bovine serum albumin resulted in clenbuterol-specific cellular uptake predominantly into alveolar but not bronchial epithelial cells. Clen- g -PEI (4/1) conjugates were combined with increasing molar ratios of PEI for transfection. At optimized PEI- g -Clen/PEI composition, transfection efficiency on alveolar epithelial cells was up to 14-fold higher than for unmodified PEI and could be inhibited by an excess of free clenbuterol. No increase of transfection efficiency was observed on bronchial epithelial cells. Increasing the PEI- g -Clen/PEI molar ratio resulted in an increase of gene vector size, decrease of the zeta potential and cytotoxicity. Aerosol delivery of optimized PEI- g -Clen/PEI (1/5) gene vectors resulted in a significant 3-fold increase of gene expression in the lungs of mice compared with unmodified PEI gene vectors. We suggest that coupling of β 2 -adrenoceptor ligands to nonviral gene vectors represents a promising approach to improve gene delivery to the lungs.
Keywords:
- Correction
- Source
- Cite
- Save
- Machine Reading By IdeaReader
25
References
44
Citations
NaN
KQI