Effect of Molecular Weight on Sonoporation-Mediated Uptake in Human Cells

Bhutto, Danyal F.; Murphy, Emily M.; Priddy, Mariah C.; Centner, Connor S.; Moore, Joseph B.; Bolli, Roberto; Kopechek, Jonathan A.

doi:10.1016/j.ultrasmedbio.2018.08.008

Cited by 17 publications

(10 citation statements)

References 31 publications

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“…Previous findings suggest that the sonoporation effect has a duration of up to and exceeding one hour [20,35,36], supports our choice of 60 min drug incubation time in our experiments. Also, shorter incubation times could have been relevant in order to establish a dynamic range and thus detect more subtle changes in sonoporation-induced cellular gemcitabine uptake.…”

Section: Duration Of Incubationsupporting

confidence: 86%

“…The majority of in vitro research on US and microbubble assisted drug delivery has been performed using fluorescence labelled dyes that have no routes of spontaneous cellular entry [20][21][22]. As such, they are ideal model drugs for mechanistic studies and for optimisation of sonoporation settings.…”

Section: Implications Strengths and Limitationsmentioning

confidence: 99%

“…Furthermore, the static in vitro environment does not mimic the blood flow seen in vivo. A dynamic blood flow would drastically reduce the contact between microbubbles and cells [55] and also affect how the cells grow [20]. The protein concentration in cell culture media are also low compared to blood, meaning the microbubbles may have an increased stability as the proteins reduce the hydrophobicity of the lipids [56].…”

Section: Implications Strengths and Limitationsmentioning

confidence: 99%

“…It was postulated that the observed effects might partly be explained by increased gemcitabine delivery to PDAC tumour cells. This hypothesis was based on prior in vitro experiments in which cell-impermeable fluorescent drug surrogates had been shown to enter cells exposed to sonoporation [20][21][22].…”

Section: Introductionmentioning

confidence: 99%

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Ultrasound- and Microbubble-Assisted Gemcitabine Delivery to Pancreatic Cancer Cells

Bjånes

Kotopoulis

Murvold³

et al. 2020

Pharmaceutics

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Pancreatic ductal adenocarcinoma (PDAC) is a major cause of cancer death worldwide. Poor drug delivery to tumours is thought to limit chemotherapeutic treatment efficacy. Sonoporation combines ultrasound (US) and microbubbles to increase the permeability of cell membranes. We assessed gemcitabine uptake combined with sonoporation in vitro in three PDAC cell lines (BxPC-3, MIA PaCa-2 and PANC-1). Cells were cultured in hypoxic bioreactors, while gemcitabine incubation ± sonoporation was conducted in cells with operational or inhibited nucleoside membrane transporters. Intracellular active metabolite (dFdCTP), extracellular gemcitabine, and inactive metabolite (dFdU) concentrations were measured with liquid chromatography tandem mass spectrometry. Sonoporation with increasing US intensities resulted in decreasing extracellular gemcitabine concentrations in all three cell lines with inhibited membrane transporters. In cells with inhibited membrane transporters, without sonoporation, dFdCTP concentrations were reduced down to 10% of baseline. Sonoporation partially restored gemcitabine uptake in these cells, as indicated by a moderate increase in dFdCTP concentrations (up to 37% of baseline) in MIA PaCa-2 and PANC-1. In BxPC-3, gemcitabine was effectively inactivated to dFdU, which might represent a protective mechanism against dFdCTP accumulation in these cells. Intracellular dFdCTP concentrations did not change significantly following sonoporation in any of the cell lines with operational membrane transporters, indicating that the gemcitabine activation pathway may have been saturated with the drug. Sonoporation allowed a moderate increase in gemcitabine transmembrane uptake in all three cell lines, but pre-existing nucleoside transporters were the major determinants of gemcitabine uptake and retention.

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Section: Duration Of Incubationsupporting

confidence: 86%

Section: Implications Strengths and Limitationsmentioning

confidence: 99%

Section: Implications Strengths and Limitationsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Ultrasound- and Microbubble-Assisted Gemcitabine Delivery to Pancreatic Cancer Cells

Bjånes

Kotopoulis

Murvold³

et al. 2020

Pharmaceutics

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“…Studies had shown that fluorescent molecules (e.g. FITC) can penetrate to the cytosol through the pores caused by UTMD (De Cock et al, 2015 ; Song et al, 2015 ; Bhutto et al, 2018 ). To examine the optimum parameters for UTMD-enhanced miR-34a-mimic delivery, 150 kDa Fluorescein isothiocyanate-labeled dextran (FITC-dextran, Sigma-Aldrich Co. LLC, Shanghai, China) was used as model molecules for the evaluation of UTMD-mediated sonoporation efficiency.…”

Section: Methodsmentioning

confidence: 99%

UTMD promoted local delivery of miR-34a-mimic for ovarian cancer therapy

Fang

et al. 2021

Drug Delivery

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MicroRNA-mediated gene therapy is emerging as a promising method for the treatment of ovarian cancer, but the development of miRNA mimic delivery vectors is still in its infancy, where the safety and efficacy of miR-34a-mimic remain unknown. Ultrasound-targeted microbubble destruction (UTMD) can be an effective and minimally invasive tool for the delivery of miR-34a-mimic in vitro and in vivo . Here, we describe a high-efficiency gene delivery strategy by using miR-34a-mimic loaded folate modified microbubbles (miR-34a-FM) with a portable ultrasonic irradiation system. Ultrasonic parameters, including acoustic intensity (AI), exposure time (ET) and duty cycle (DC), were optimized and the optimal acoustic condition (1.0 W/cm 2 , 20 s, and 15% DC) was used to deliver miRNA-34a into cells in vitro. MiR-34a mimic was successfully introduced into the cytoplasm and was found to inhibit proliferation and induce apoptosis of SK-OV-3 cells. Next, miR-34a-mimic was delivered to tumor tissue via UTMD, inhibiting tumor growth and prolonging the survival time of mice. In summary, UTMD-mediated miR-34a-mimic delivery has potential application in the clinical treatment of ovarian cancer.

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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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Effect of Molecular Weight on Sonoporation-Mediated Uptake in Human Cells

Cited by 17 publications

References 31 publications

Ultrasound- and Microbubble-Assisted Gemcitabine Delivery to Pancreatic Cancer Cells

Ultrasound- and Microbubble-Assisted Gemcitabine Delivery to Pancreatic Cancer Cells

UTMD promoted local delivery of miR-34a-mimic for ovarian cancer therapy

Sonoporation: Past, Present, and Future

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