Ultrasound-Mediated Drug Delivery: Sonoporation Mechanisms, Biophysics, and Critical Factors

Abstract

Sonoporation, or the use of ultrasound in the presence of cavitation nuclei to induce plasma membrane perforation, is well considered as an emerging physical approach to facilitate the delivery of drugs and genes to living cells. Nevertheless, this emerging drug delivery paradigm has not yet reached widespread clinical use, because the efficiency of sonoporation is often deemed to be mediocre due to the lack of detailed understanding of the pertinent scientific mechanisms. Here, we summarize the current observational evidence available on the notion of sonoporation, and we discuss the prevailing understanding of the physical and biological processes related to sonoporation. To facilitate systematic understanding, we also present how the extent of sonoporation is dependent on a multitude of factors related to acoustic excitation parameters (ultrasound frequency, pressure, cavitation dose, exposure time), microbubble parameters (size, concentration, bubble-to-cell distance, shell composition), and cellular properties (cell type, cell cycle, biochemical contents). By adopting a science-backed approach to the realization of sonoporation, ultrasound-mediated drug delivery can be more controllably achieved to viably enhance drug uptake into living cells with high sonoporation efficiency. This drug delivery approach, when coupled with concurrent advances in ultrasound imaging, has potential to become an effective therapeutic paradigm.

Delivering the CRISPR/Cas9 system for engineering gene therapies: Recent cargo and delivery approaches for clinical translation

“…At low pressures, the microbubbles undergo stable cavitation, where the magnitude of their oscillating size is inversely proportional to the localized acoustic pressure and disruption to the cell membrane, whereas at high pressures, bubbles undergo inertial cavitation, resulting in large, asymmetric bubble size oscillation and the formation of penetrating liquid jets, as illustrated in Figure 3B . The efficiency of sonoporation is dependent on cellular properties as well as acoustic excitation and microbubble parameters, the understanding of which can increase efficiency and controllability of the system ( Tu and Yu, 2022 ). One such example where acoustoporation was applied to transfect pDNA encoding Cas9 and gRNA to human endometrial cancer (HEC)-1A cells is the work of Cai et al (2019) , who reported a 57% decrease of mRNA expression from the target knockout c-erbB2.…”

Sonoporation of Immune Cells: Heterogeneous Impact on Lymphocytes, Monocytes and Granulocytes

“…For instance, it would be worthwhile to profile the immunophenotype of sonoporated leukocytes and analyze the relevant cytokine levels to gain a deeper understanding of the post-sonoporation cytological differences between the three leukocyte subsets. Other biological factors may also be involved in influencing the level of sonoporation-induced cellular uptake and post-sonoporation viability (Shi et al 2017;Haugse et al 2020;Tu and Yu 2022). Nevertheless, not all of these previously identified biological factors are applicable to leukocytes.…”

Optimized acoustic streaming generated at oblique incident angles to improve ultrasound thrombolysis effect

“…In recent years, ultrasound (US) waves have shown its great potential in clinical diagnosis and therapy 15–17 . More specific applications in thrombolysis include microbubbles (MBs) 18 or nanodroplets (NDs) 19 mediated US thrombolysis, catheter‐mediated US thrombolysis, 20–22 dual frequency US thrombolysis, 23 and so on.…”

“…In recent years, ultrasound (US) waves have shown its great potential in clinical diagnosis and therapy. [15][16][17] More specific applications in thrombolysis include microbubbles (MBs) 18 or nanodroplets (NDs) 19 mediated US thrombolysis, catheter-mediated US thrombolysis, [20][21][22] dual frequency US thrombolysis, 23 and so on. Among them, US thrombolysis using MBs or NDs has the merits of convenience and utility as it can be carried out well with standard products and instruments available to doctors.…”