Thiolated polyethylenimine (PEI) polymers can be covalently attached to lipid shell microbubbles. The PEI polymer can be modified with polyethylene glycol (PEG) chains to improve biocompatibility. The covalent attachment of the PEI polymer to the microbubble shell can result from a bond between a free sulfhydryl group (SH) of the thiolated PEI and a free maleimide group on the microbubble shell. DNA can be electrostatically bound to the PEI polymers to form polyplexes. A plurality of the polyplex-microbubble hybrids can be injected into a patient and can be imaged via ultrasound. While circulating in the bloodstream, and in particular, within a region of interest, high-pressure, low-frequency acoustic energy can be applied, thereby causing destruction by cavitation. Such cavitation can transiently increase the permeability of the endothelial vasculature thereby allowing plasmid DNA of the polyplexes carried by the microbubbles to be delivered to targeted cells.
