1.O.3. The Sonoporation-induced Pore (SiP) Family
Sonoporation uses ultrasound and can be used to deliver compounds into viable cells for potential targeted drug delivery and non-viral gene transfection, revealing advantageous possibilities. The delivery is facilitated through sonoporation, the formation of temporary pores in the cell membrane induced by ultrasound. Pan et al. 2004 and Pan et al. 2005 reviewed sonoporation mechanisms that can be used to achieve optimal delivery outcomes such as high delivery efficiency and minimal cell death. Using voltage clamp techniques, they obtained real-time measurements of sonoporation of single Xenopus oocytes in the presence of Optison, an agent consisting of albumin-shelled C3F8 gas bubbles. Ultrasound (US) increased the transmembrane current as a direct result of decreased membrane resistance due to pore formation. Using voltage clamp techniques, Deng et al. 2004 obtained real-time measurements of sonoporation of single Xenopus oocyte in the presence of Optison trade mark, an agent consisting of albumin-shelled C(3)F(8) gas bubbles (mean diameter 3.2 micrometers). Ultrasound increased the transmembrane current as a direct result of decreased membrane resistance due to pore formation. Deng et al. 2004 observed a distinct delay of sonoporation following US activation and characteristic stepwise increases of transmembrane current throughout US duration. They discovered that the resealing of the cell membrane following US exposure required Ca2+ entering the cell through US-induced pores.
Sonoporation generates transient nonselective pores in cell membranes. This technique has been used for nonviral intracellular drug, protein and gene delivery, and the pore size determines the size of agents that can be delivered into the cytoplasm. Electron microscopy and atomic force microscopy have been used to gauge pore size, but changes of the transmembrane current of a single cell under voltage clamp conditions can be used for monitoring pore formation and pore size. Using Xenopus laevis oocytes, the current of single cells was measured in real-time by Zhou et al. 2009 to assess formation of pores. The mean radius of single sonopores was about 110 or 40 nm.
The ability to real time monitor sonoporation of cells provides a novel tool to study the dynamic sonoporation process and obtain optimal delivery parameters. Sonoporation mechanisms have been reviewed (Bouakaz et al. 2016; Dasgupta et al. 2016; Castle and Feinstein 2016).