The role of ultrasound in medicine and biological sciences is expanding rapidly beyond its use in conventional diagnostic imaging. Numerous studies have reported the effects of ultrasound on cellular and tissue physiology. Advances in instrumentation and electronics have enabled successful in vivo applications of therapeutic ultrasound. Despite path breaking advances in understanding the biophysical and biological mechanisms at both microscopic and macroscopic scales, there remain substantial gaps. With the progression of research in this area, it is important to take stock of the current understanding of the field and to highlight important areas for future work. We present herein key developments in the biological applications of ultrasound especially in the context of nanoparticle delivery, drug delivery, and regenerative medicine. We conclude with a brief perspective on the current promise, limitations, and future directions for interfacing ultrasound technology with biological systems, which could provide guidance for future investigations in this interdisciplinary area.

DNA nanotechnology utilizes DNA as a structural molecule to design palette of nanostructures with different shapes and sizes. DNA nanocages have demonstrated significant potential for drug delivery. Therefore, enhancing the delivery of DNA nanocages into cells can improve their efficacy as drug delivery agents. Numerous studies have reported the effects of ultrasound for enhancing drug delivery across biological barriers. The mechanical bioeffects caused by cell-ultrasound interaction can cause sonoporation, leading to enhanced uptake of drugs, nanoparticles, and chemotherapeutic agents through membranes. Whether ultrasound exposure can enhance the delivery of DNA nanocages has not been explored, which is the focus of this study. Specifically, we investigated the effects of ultrasound on the cellular uptake of propidium Iodide, fluorescent dextrans, and DNA nanostructures). We provide evidence of modulation of pore formation in the cell membrane by ultrasound by studying the intracellular uptake of the impermeable dye, propidium iodide. Treatment of cells with low amplitudes of ultrasound enhanced the uptake of different sizes of dextrans and DNA based nanodevices. These findings could serve as the foundation for further development ultrasound-enabled DNA nanostructure delivery and for specific understanding of underlying biological mechanisms of interaction between ultrasound parameters and cellular components; the knowledge that can be further explored for potential biological and biomedical applications.