Controlled Release of Fe3O4 Nanoparticles in Encapsulated Microbubbles to Tumor Cells via Sonoporation and Associated Cellular Bioeffects

Fe(3)O(4) nanoparticles embedded in the shells of encapsulated microbubbles could be used therapeutically as in situ drug-delivery vehicles. Bioeffects on liver tumor cells SMMC-7721 due to the excitation of Fe(3)O(4) nanoparticles attached to microbubbles generated by ultrasound (US) are studied in an in vitro setting. The corresponding release phenomenon of Fe(3)O(4) nanoparticles from the shells of the microbubbles into the cells via sonoporation and related phenomena, including nanoparticle delivery efficiency, cell trafficking, cell apoptosis, cell cycle, and disturbed flow of intracellular calcium ions during this process, are also studied. Experimental observations show that Fe(3)O(4) nanoparticles embedded in the shells of microbubbles can be delivered into the tumor cells; the delivery rate can be controlled by adjusting the acoustic intensity. The living status or behavior of Fe(3)O(4) -tagged tumor cells can then be noninvasively tracked by magnetic resonance imaging (MRI). It is further demonstrated that the concentration of intracellular Ca(2+) in situ increases as a result of sonoporation. The elevated Ca(2+) is found to respond to the disrupted site in the cell membrane generated by sonoporation for the purpose of cell self-resealing. However, the excessive Ca(2+) accumulation on the membrane results in disruption of cellular Ca(2+) cycling that may be one of the reasons for the death of the cells at the G1 phase. The results also show that the Fe(3)O(4) -nanoparticle-embedded microbubbles have a lower effect on cell bioeffects compared with the non-Fe(3)O(4) -nanoparticle-embedded microbubbles under the same US intensity, which is beneficial for the delivery of nanoparticles and simultaneously maintains the cellular viability.