Duration of ultrasound-mediated enhanced plasma membrane permeability

Lammertink, Bart; Deckers, Roel; Storm, Gerrit; Moonen, Chrit; Bos, Clemens

doi:10.1016/j.ijpharm.2014.12.013

Cited by 53 publications

(50 citation statements)

References 34 publications

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“…The absence of thermal effects as a consequence of adjusting parameters such as duty cycle, ultrasound exposure time, and frequency has been reported by others with ultrasound settings similar to those used in this work. [43][44][45][46] For example, our ultrasound exposure was pulsed at a duty cycle of 30% for 20-60 s compared to continuous ultrasound irradiation for 5-10 mins as reported in the studies referred before. Therefore, it is thought that the presence of nanoparticles during ultrasound irradiation did not contribute thermal effects and the main contribution to mechanical effect, most likely stable cavitation, produced by Definity ® microbubbles in the culture medium.…”

Section: Discussionmentioning

confidence: 99%

<p>In vitro Ultrasonic Potentiation of 2-Phenylethynesulfonamide/Magnetic Fluid Hyperthermia Combination Treatments for Ovarian Cancer</p>

Mérida¹,

Rinaldi²,

Juan³

et al. 2020

IJN

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Background: Magnetic Fluid Hyperthermia (MFH) is a promising adjuvant for chemotherapy, potentiating the action of anticancer agents. However, drug delivery to cancer cells must be optimized to improve the overall therapeutic effect of drug/MFH combination treatments. Purpose: The aim of this work was to demonstrate the potentiation of 2-phenylethynesulfonamide (PES) at various combination treatments with MFH, using low-intensity ultrasound as an intracellular delivery enhancer. Methods: The effect of ultrasound (US), MFH, and PES was first evaluated individually and then as combination treatments. Definity ® microbubbles and polyethylene glycol (PEG)-coated iron oxide nanoparticles were used to induce cell sonoporation and MFH, respectively. Assessment of cell membrane permeabilization was evaluated via fluorescence microscopy, iron uptake by cells was quantified by UV-Vis spectroscopy, and cell viability was determined using automatic cell counting. Results: Notable reductions in cancer cell viability were observed when ultrasound was incorporated. For example, the treatment US+PES reduced cell viability by 37% compared to the non-toxic effect of the drug. Similarly, the treatment US+MFH using mild hyperthermia (41°C), reduced cell viability by an additional 18% when compared to the effect of MH alone. Significant improvements were observed for the combination of US+PES+MFH with cell viability reduced by an additional 26% compared to the PES+MFH group. The improved cytotoxicity was attributed to enhanced drug/nanoparticle intracellular delivery, with iron uptake values nearly twice those achieved without ultrasound. Various treatment schedules were examined, and all of them showed substantial cell death, indicating that the time elapsed between sonoporation and magnetic field exposure was not significant. Conclusion: Superior cancer cell-killing patterns took place when ultrasound was incorporated thus demonstrating the in vitro ultrasonic potentiation of PES and mild MFH. This work demonstrated that ultrasound is a promising non-invasive enhancer of PES/MFH combination treatments, aiming to establish a sono-thermo-chemotherapy in the treatment of ovarian cancer.

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Section: Discussionmentioning

confidence: 99%

<p>In vitro Ultrasonic Potentiation of 2-Phenylethynesulfonamide/Magnetic Fluid Hyperthermia Combination Treatments for Ovarian Cancer</p>

Mérida¹,

Rinaldi²,

Juan³

et al. 2020

IJN

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show abstract

“…Ultrasound is known to promote membrane permeability, thus increasing intracellular drug accumulation. Previous studies have suggested that the mechanisms by which ultrasound enhances the cytotoxicity of chemotherapy drugs include increased generation of reactive oxygen species [10,11], intracellular drug accumulation [12,13], and cell membrane permeability [14,15,16]. The combined therapy concentration and sufficient exposure time were crucial to the chemotherapeutic efficacy in our study.…”

Section: Discussionmentioning

confidence: 55%

Low-Frequency Ultrasound Enhances Paclitaxel Efficacy in EMT6 Subcutaneous Tumors in Balb/c Mice

Weng¹,

Chen

Zhao

et al. 2016

Oncol Res Treat

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Background: The objective of this study was to explore the effects of 30 kHz ultrasound on the efficacy of paclitaxel in subcutaneous breast tumors in Balb/c mice in vivo. Materials and Methods: 40 Balb/c female mice were divided into 5 groups: model control group, paclitaxel intraperitoneal (ip) group (20 mg/kg, ip, at 3 day intervals for a total of 3 doses (q3d×3)), paclitaxel intratumoral (it) group (20 mg/kg, it, q3d×3), paclitaxel intraperitoneal (20 mg/kg, ip, q3d×3) combined with low-frequency ultrasound (LFU) group, and paclitaxel intratumoral (20 mg/kg, it, q3d×3) combined with LFU group. Ultrasound parameters were 30 kHz, 200 MW intensity, 15 min, q3d×3. The antitumoral effect was determined by examining the tumor weight in subcutaneously inoculated EMT6 breast carcinoma models in Balb/c mice. All subcutaneous tumors were examined using high performance liquid chromatography (HPLC) upon completion of the experiments. Drug concentrations in the subcutaneous tumors were also analyzed using HPLC. Finally, paraffin sections of the subcutaneous tumors were made, and after hematoxylin and eosin staining, the tumor morphology was examined under a light microscope. Results: LFU combined with paclitaxel significantly restrained tumor growth in transplanted subcutaneous EMT6 tumors in Balb/c mice, and this effect correlated with increased local concentrations of paclitaxel in the tumors. Body weight measurement did not reveal significant adverse effects on the Balb/c mice during the study. Conclusion: LFU combined with paclitaxel has a significant synergistic effect in the treatment of breast cancer.

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“…Second, ultrasound mediated cavitation facilitates rapid release of therapeutics, reduced time for localized drug delivery, increased drug accumulation at the disease site, and enhanced bioactivities for anticancer agents333435. Third, ultrasound fragmentation of the microdroplets generates physical forces, shock waves, microjets, and microstreamings to increase the permeability of cell membranes for intracellular uptake of drugs3637. Fourth, oxygen released from the SRMs provides an oxygen-enriched environment and increases sensitivity for many anticancer therapies838.…”

Section: Discussionmentioning

confidence: 99%

Ultrasound mediated delivery of oxygen and LLL12 loaded stimuli responsive microdroplets for the treatment of hypoxic cancer cells

Yuan

Tian

et al. 2017

Sci Rep

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LLL12 exhibits high specificity for inhibiting STAT3 phosphorylation and dimerization, and inducing apoptosis to constitutively activated STAT3 cancer cells without cytotoxicity to normal cells with dormant STAT3. However, clinical deployment of LLL12 in cancer treatment is hindered by its low bioavailability and hypoxia-induced resistance. To overcome these limitations, we encapsulate both oxygen and LLL12 in stimuli responsive microdroplets (SRMs) by a gas-driven coaxial flow focusing (CFF) process for ultrasound mediated treatment of hypoxic cancer cells. Our benchtop experiments demonstrate that the CFF process is able to produce SRMs with uniform size distribution, large oxygen loading capacity, high LLL12 encapsulation efficiency, well protection of bioactivity, and steadily long shelf time. The in vitro therapeutic studies in pancreatic cancer cells (PANC-1 and CAPAN-1) demonstrate the immediate release of oxygen and LLL12 in exposure to therapeutic ultrasound pulses as well as the improved anticancer effects under hypoxic conditions. The findings suggest that the proposed oxygen and LLL12 loaded SRMs provide a promising drug delivery strategy for more effective treatment of hypoxic cancer cells.

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Duration of ultrasound-mediated enhanced plasma membrane permeability

Cited by 53 publications

References 34 publications

<p>In vitro Ultrasonic Potentiation of 2-Phenylethynesulfonamide/Magnetic Fluid Hyperthermia Combination Treatments for Ovarian Cancer</p>

<p>In vitro Ultrasonic Potentiation of 2-Phenylethynesulfonamide/Magnetic Fluid Hyperthermia Combination Treatments for Ovarian Cancer</p>

Low-Frequency Ultrasound Enhances Paclitaxel Efficacy in EMT6 Subcutaneous Tumors in Balb/c Mice

Ultrasound mediated delivery of oxygen and LLL12 loaded stimuli responsive microdroplets for the treatment of hypoxic cancer cells

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