Efficacy optimization of low frequency microbubble-mediated sonoporation as a drug delivery platform to cancer cells

Eck, Michal; Aronovich, Ramona; Ilovitsh, Tali

doi:10.1016/j.ijpx.2022.100132

Cited by 14 publications

(18 citation statements)

References 61 publications

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“…These phantoms may provide an alternative to computerized flow simulations used to evaluate localization and tracking accuracy by creating shapes that are challenging to reproduce with ULM, such as the horseshoe shape . We believe these phantoms can be used to study a wide variety of applicationssuch as the verification of contrast-enhanced harmonic imaging, resolution-improving ultrasound algorithms, and the behavior of bubble flow in therapeutic applications. – …”

Section: Discussionmentioning

confidence: 99%

Versatile Ultrasound-Compatible Microfluidic Platform for In Vitro Microvasculature Flow Research and Imaging Optimization

Mano,

Grutman,

Ilovitsh

2023

ACS Omega

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Ultrasound localization microscopy (ULM) enables the creation of super-resolved images and velocity maps by localizing and tracking microbubble contrast agents through a vascular network over thousands of frames of ultrafast plane wave images. However, a significant challenge lies in developing ultrasound-compatible microvasculature phantoms to investigate microbubble flow and distribution in controlled environments. In this study, we introduce a new class of gelatin-based microfluidic-inspired phantoms uniquely tailored for ULM studies. These devices allow for the creation of complex and reproducible microvascular networks featuring channel diameters as small as 100 μm. Our experiments focused on microbubble behavior under ULM conditions within bifurcating and converging vessel phantoms. We evaluated the impact of bifurcation angles (25, 45, and 55°) and flow rates (0.01, 0.02, and 0.03 mL/min) on the acquisition time of branching channels. Additionally, we explored the saturation time effect of narrow channels branching off larger ones. Significantly longer acquisition times were observed for the narrow vessels, with an average increase of 72% when a 100 μm channel branched off from a 300 μm channel and an average increase of 90% for a 200 μm channel branching off from a 500 μm channel. The robustness of our fabrication method is demonstrated through the creation of two trifurcating microfluidic phantoms, including one that converges back into a single channel, a configuration that cannot be achieved through traditional methods. This new class of ULM phantoms serves as a versatile platform for noninvasively studying complex flow patterns using ultrasound imaging, unlocking new possibilities for in vitro microvasculature research and imaging optimization.

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Section: Discussionmentioning

confidence: 99%

Versatile Ultrasound-Compatible Microfluidic Platform for In Vitro Microvasculature Flow Research and Imaging Optimization

Mano,

Grutman,

Ilovitsh

2023

ACS Omega

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“…This pattern is in line with the results obtained for TMB-mediated sonoporation, where uptake was diminished for larger molecules. 33 In these experiments, we implemented a sham control group that was subjected to the exact same conditions as the treatment groups, including incubation with FITC. If any cells took up FITC during the 24-hour incubation period, this would result in an increase across all groups.…”

Section: Discussionmentioning

confidence: 99%

“…It should be noted that there is a significant difference between MBs and NBs in the context of in vitro assays, because proximity to the cells plays a crucial role. 33,63 MBs tend to float, which accounts for the lack of increased uptake after free MBs insonation. In a previous study, it was shown that free MBs + US did not affect cell viability.…”

Section: Discussionmentioning

confidence: 99%

“…[28][29][30][31][32] By exploiting this effect, we developed MB-mediated sonoporation for large molecules delivery to cancer cells. 33 For tumor therapy application in vivo, the MB were intratumorally injected, making it an invasive approach. 32 In addition, we showed that since MBs are buoyant and close proximity to the cells is required, targeted MBs (TMBs) were used.…”

Section: Introductionmentioning

confidence: 99%

“…32 In addition, we showed that since MBs are buoyant and close proximity to the cells is required, targeted MBs (TMBs) were used. 32,33 Here we report the development of a noninvasive NB-mediated cancer cell sonoporation platform. Recently we showed that the Blake threshold is also applicable to nanoscale bubbles, and causes violent NB oscillations at center frequencies below 250 kHz.…”

Section: Introductionmentioning

confidence: 99%

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