Ultrasound-induced molecular delivery to erythrocytes using a microfluidic system

Centner, Connor S.; Murphy, Emily M.; Priddy, Mariah C.; Moore, John; Janis, Brett; Menze, Michael A.; DeFilippis, Andrew P.; Kopechek, Jonathan A.

doi:10.1063/1.5144617

Cited by 23 publications

(8 citation statements)

References 49 publications

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“…36−39 Evaluation of this approach in phase I clinical trials, although in a limited number of patients with pancreatic and hepatic cancer, has generated interesting results in terms of safety and drug clinical efficiency. 40,41 In a recent study using ultrasound in the presence of microbubbles and erythrocytes as carriers, increased trehalose uptake, an effective sugar for protection against desiccation, has been demonstrated by Centner et al 42 with improvement of recovery of viable erythrocytes following freeze-drying and rehydration. The presented study is in the continuity of our previous publications exploiting the strong potential of ultrasound as an alternative tool for drug and nucleic acids delivery.…”

Section: ■ Discussionmentioning

confidence: 97%

Proof of Concept: Protein Delivery into Human Erythrocytes Using Stable Cavitation

et al. 2022

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Human erythrocytes represent candidates of choice as carriers for a wide range of drugs due to their unique biophysical and physiological properties. In this study, we used a sonoporation device generating and monitoring acoustic stable cavitation without any addition of contrast or nucleation agents. The device was evaluated for bovine serum albumin (BSA) delivery into human erythrocytes. After determining the adequate hematocrit percentage compatible with the generation of stable cavitation, we determined the optimal sonoporation conditions allowing BSA delivery while preserving erythrocyte integrity. Our results demonstrate that stable cavitation allows efficient delivery of proteins into human erythrocytes with limited lysis of these cells. In conclusion, our study allowed for the development of a stable and regulated cavitation program and the establishment of sonoporation conditions suitable for intracellular protein delivery while maintaining erythrocyte integrity. Additional investigations are needed to move from the proof of concept to a larger-scale application.

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Section: ■ Discussionmentioning

confidence: 97%

Proof of Concept: Protein Delivery into Human Erythrocytes Using Stable Cavitation

et al. 2022

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“…This cavitation phenomenon is adopted to create membrane discontinuities by imposing shear force on the cells. [98,101] In the following sections, we will briefly discuss acoustic-and laser-assisted cavitation techniques and describe how they have been integrated with microfluidics for advanced intracellular delivery.…”

Section: Cavitationmentioning

confidence: 99%

Microfluidic and Nanofluidic Intracellular Delivery

Hur

Chung

2021

Advanced Science

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Innate cell function can be artificially engineered and reprogrammed by introducing biomolecules, such as DNAs, RNAs, plasmid DNAs, proteins, or nanomaterials, into the cytosol or nucleus. This process of delivering exogenous cargos into living cells is referred to as intracellular delivery. For instance, clustered regularly interspaced short palindromic repeats (CRISPR)‐Cas9 gene editing begins with internalizing Cas9 protein and guide RNA into cells, and chimeric antigen receptor‐T (CAR‐T) cells are prepared by delivering CAR genes into T lymphocytes for cancer immunotherapies. To deliver external biomolecules into cells, tools, including viral vectors, and electroporation have been traditionally used; however, they are suboptimal for achieving high levels of intracellular delivery while preserving cell viability, phenotype, and function. Notably, as emerging solutions, microfluidic and nanofluidic approaches have shown remarkable potential for addressing this open challenge. This review provides an overview of recent advances in microfluidic and nanofluidic intracellular delivery strategies and discusses new opportunities and challenges for clinical applications. Furthermore, key considerations for future efforts to develop microfluidics‐ and nanofluidics‐enabled next‐generation intracellular delivery platforms are outlined.

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“…In addition to trapping bubbles, Centner et al leveraged a spiral microfluidic channel to enhance cell and bubble residence time in the sonicating bath region of interest. [131] As shown in Figure 3d,e, their setup can be considered as a modified version of the conventional bubble-based setup in Figure 2, by changing the chamber containing cells to a spiral microfluidic channel with flowing cells. Compared to conventional setups, their device can achieve sonoporation for cells in a continuous flow for potential high-throughput applications.…”

Section: Recent Bubble-based Microfluidic Technologiesmentioning

confidence: 99%

“…(e) Reproduced with permission. [131] Copyright 2020, Biomicrofluidics. f) A schematic of a setup that leverages surface acoustic wave-based acoustic tweezers to precisely move a microbubble to a target cell and then apply an acoustic pulse to enable inertial bubble cavitation at the cell location for sonoporation.…”

Section: Non-bubble-based Mechanismsmentioning

confidence: 99%

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Sonoporation: Past, Present, and Future

Rich

Tian

Huang

2021

Adv Materials Technologies

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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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Ultrasound-induced molecular delivery to erythrocytes using a microfluidic system

Cited by 23 publications

References 49 publications

Proof of Concept: Protein Delivery into Human Erythrocytes Using Stable Cavitation

Proof of Concept: Protein Delivery into Human Erythrocytes Using Stable Cavitation

Microfluidic and Nanofluidic Intracellular Delivery

Sonoporation: Past, Present, and Future

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