Microarray analysis of cationic nanoliposomes genocompatibility in human alveolar epithelial cells

Gene toxicology (particularly genocompatibility and/or toxicogenomics) has begun to be acknowledged as an important scientific discipline in drug delivery and targeting, in which the intrinsic genomic signature of chemicals and pharmaceuticals is going to be underlined in the heredity of living organisms for a better implementation of such pharmaceuticals. Viral and non-viral vectors are the two paradigms for transport of genome-based pharmaceuticals in vitro and in vivo. However, genomic impact(s) of these delivery systems in target cells/tissues are still in shed of their transfection potential. Despite substantial information on their cellular influence, little information is available about the genocompatibility and/or toxicogenomics of the non-viral vectors including cationic lipid (CL) delivery systems. In the current study, we investigated the genocompatibility of cationic lipid, Oligofectamine (OF) in human alvelolar epithelial A549 cell line. To screen the genomic impact(s) of these delivery systems, cytotoxicity assay using MTT and DNA microarray technology was utilized. RNA samples from treated (routinely used concentrations of CL) and untreated cells were converted to aminoallyl-cDNA, labeled with cyanine (Cy3/Cy5) and hybridized on target arrays housing 200 gene spots. Slid arrays were scanned, data was normalized and up- and down-regulated genes and their ontologies were detected. MTT assay showed cytotoxicity within A549 cells treated with the nanoliposomes. The gene expression profiles revealed marked changes (≥2-fold) in gene expression for 8-15% of genes from various genomic ontologies induced by OF. Among altered genes, some (e.g., il9r, ces111 and tnfsf6) were related to the apoptosis pathway; nevertheless the altered genes appeared to be within various gene ontologies. Our findings highlight pervasiveness of intrinsic genomic impacts by cationic nanoliposomes. Such impacts may interfere with the main goals of these delivery systems by masking/stimulating a cluster of non-specific genes that may affect the end point genotype and/or phenotype, thus we suggest genomic assessments for cationic liposome gene delivery systems.