Sonoporation: Past, Present, and Future

Abstract

only contribute to fundamental studies in areas of biology, bioengineering, and medicine, but also benefit several life-changing technologies, such as cell-based therapies, protein therapeutics, vaccines, as well as the reprogramming of cells. [22] Among the current delivery approaches, the viral vector-based approach is often considered the gold standard for the delivery of nucleic acids. [22] However, due to notable weaknesses such as biohazards, inconsistent results, and labor-intensive manufacturing, [22][23][24] physical permeabilization approaches are being pursued, [1][2][3][4][5][6][7][8][9][10][11][12]22] including electroporation, [25,26] hydroporation, [27][28][29][30][31][32] mechanoporation, [25,[32][33][34][35][36][37][38][39][40] and sonoporation. [41,42] These approaches are noted as advanced due to their high throughputs, cost-effectiveness, and universal nature to deliver a variety of cargos regardless of cell type. [3] Of the physical permeabilization approaches, sonoporation wields great potential and has been demonstrated as an efficacious technology for delivering a variety of functional cargos, such as biomolecular drugs, proteins, and plasmids, to different types of cells, such as cancer, immune, and stem cells. [43][44][45][46][47][48] Sonoporation was discovered in the 1980s, a golden age of intracellular delivery, in which quite a few physical permeabilization methods were invented. [49][50][51][52][53][54][55][56][57][58] Sonoporation enhances the intracellular delivery of cargos into cells by employing acoustic waves to disrupt their membranes. [22,[59][60][61][62] Traditional sonoporation approaches typically rely on ultrasound-induced bubble dynamic behaviors, such as inertial cavitation, noninertial (stable) cavitation, and bubble translation. [49][50][51][52] However, the bubble-based sonoporation approaches usually require special contrast agents, [63][64][65][66][67][68] which adds a new dimension of complexity and cost to the use of sonoporation. Moreover, bubble-based approaches have a high chance of inducing irreversible cell damage, lowering the cell viability, as well as reducing the effectiveness of delivered cargos. [69][70][71][72][73] Therefore, several novel non-bubble-based sonoporation approaches, such as those based on acoustic radiation force and acoustic streaming-induced shear force, are being developed to overcome the limitations of bubble-based sonoporation approaches. Although there are several review papers on the mechanisms and applications of bubble-based sonoporation, [61,62,[74][75][76][77][78][79][80][81][82][83][84][85][86][87][88] they have neglected some of the newly developed mechanisms. Therefore, this review article covers recent innovations in bubble-based and especially in non-bubble-based sonoporation. The following sections review the sonoporation mechanisms, A surge of research in intracellular delivery technologies is underway with the increased innovations in cell-based therapies and cell reprogramming. Particularly, physical cell membrane p...

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