Ultrasound-mediated membrane permeabilization (Sonoporation)

Ultrasound-mediated membrane permeabilization (sonoporation) is a non-invasive, non-viral, and non-chemical method for enhancing cellular drug delivery by temporarily increasing cell membrane permeability[1][3]. This technique utilizes ultrasound waves, often in combination with microbubbles that act as cavitation nuclei, to create transient pores in cell membranes that allow for the passage of therapeutic molecules[3][5]. The primary mechanism behind sonoporation is acoustic cavitation, where microbubbles oscillate and eventually collapse in response to ultrasound pressure waves[1][2]. This process generates mechanical forces, fluid microstreaming, and shear stresses that temporarily disrupt the cell membrane structure[3]. Direct observations using confocal microscopy have revealed that membrane perforation occurs synchronously with ultrasound pulsing, followed by a resealing process that restores membrane integrity[3]. The effectiveness of sonoporation depends on several ultrasound parameters. Studies show that membrane permeabilization increases with higher ultrasound pressure, longer exposure times (above a threshold of approximately 100 msec), and is inversely related to frequency, with lower frequencies (20-100 kHz) being more effective[1][2]. Acoustic measurements indicate that permeabilization correlates strongly with pressure measured at half the driving frequency and its ultraharmonics, as well as with broadband noise pressure, which is indicative of transient cavitation[1][2]. Microbubble properties also significantly influence sonoporation outcomes. Factors such as microbubble size, concentration, and shell materials affect the extent of membrane permeabilization[3]. Additionally, local fluid flow conditions play a role in sonoporation efficiency, with studies showing marked increases in permeabilization under higher flow rates[4]. The size of membrane pores created during sonoporation varies with acoustic pressure. At lower pressures (0.12-0.3 MPa), pore sizes range between 10-100 nm, while at higher pressures (around 1.1 MPa), pores can reach up to 1 μm in diameter[3]. While increased acoustic pressure enhances membrane permeability and transfection efficiency, it also increases the risk of cell death through immediate lysis, apoptosis, or enhanced drug cytotoxicity[3]. Sonoporation has emerged as a promising approach for delivering various therapeutic agents, including low-molecular-weight chemotherapeutic molecules, nucleic acids, therapeutic peptides, and antibodies, with clinical applications being investigated particularly in oncology and neurology[5].

Other names

SonoporationUltrasound-assisted membrane permeabilizationUltrasonic membrane permeabilizationAcoustically mediated membrane permeabilizationUltrasound-induced membrane permeabilization

Acoustic cavitation, Microbubble oscillation and collapse, Mechanical stress on cell membranes, Formation of transient pores, Generation of hydrogen peroxide, Induction of endocytosis