2-Methacryloyloxy ethyl trimethyl ammonium chloride (TMA) is a potent polymeric plasma DNA (pDNA) carrier. The present study shows that TMA/pDNA polyplexes could be internalized into cells efficiently, but could not mediate gene transfection on its own. The transfection process of TMA/pDNA polyplexes is turned on only when ultrasound (US) was applied 4–8 h after incubating TMA/pDNA polyplexes with target cells (with a gene expression 1000 times that of the immediate US group). US is a widely used physical method for gene delivery; its transfection efficiency can be significantly enhanced when combined with cationic polymer vectors. Traditionally, US is given simultaneously with genetic materials, carriers and microbubbles to exert maximal efficacy. The unique on-off phenomenon of TMA/pDNA polyplexes, controlled by US exposure, was found to relate to the endosomal escape effect of US since the polyplexes colocalized well with the lysosome marker if no US was given or was given at inappropriate times. The proposed delivery system using US and TMA carriers has potential in many pharmaceutical applications requiring precise temporal and spatial release control.
