Selecting the optimal parameters for sonoporation of pancreatic cancer in a pre-clinical model

Schultz, Christopher W.; Garibay, Gorka Ruíz de; Langer, Anika; Liu, Ji‐Bin; Dhir, Teena; Leitch, Calum; Wessner, Corinne E.; Mayoral, Mireia; Zhang, Bo; Popa, Mihaela; Huang, Chunwang; Kotopoulis, Spiros; Luo, Xianghong; Zhen, Yanhua; Niu, Sihua; Torkzaban, Mehnoosh; Wallace, Kirk; Eisenbrey, John R.; Brody, Jonathan R.; McCormack, Emmet; Forsberg, Flemming

doi:10.1080/15384047.2021.1881026

Cited by 15 publications

(7 citation statements)

References 41 publications

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“…SonoVue ® and Sonazoid™ are expected to undergo inertial cavitation at peak-negative pressures above 0.4 MPa [40,41], whereas the acoustic pressures used in this study were approximately half that. The use of stable cavitation to induce sonoporation has been shown before [17,42,43]. At these low-acoustic energy levels, an ultrasound-induced temperature rise of 0.2 °C (i.e., the TIs) is expected as the worst-case scenario; hence, ultrasound-induced hyperthermia is not expected to be the root cause of the drug delivery.…”

Section: Study Limitations and Future Workmentioning

confidence: 99%

Ultrasound and Microbubbles Enhance Uptake of Doxorubicin in Murine Kidneys

et al. 2021

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The use of ultrasound and microbubble-enhanced drug delivery, commonly referred to as sonoporation, has reached numerous clinical trials and has shown favourable results. Nevertheless, the microbubbles and acoustic path also pass through healthy tissues. To date, the majority of studies have focused on the impact to diseased tissues and rarely evaluated the impact on healthy and collateral tissue. The aim of this study was to test the effect and feasibility of low-intensity sonoporation on healthy kidneys in a mouse model. In our work here, we used a clinical diagnostic ultrasound system (GE Vivid E9) with a C1-5 ultrasound transducer combined with a software modification for 20-µs-long pulses to induce the ultrasound-guided drug delivery of doxorubicin (DOX) in mice kidneys in combination with SonoVue® and Sonazoid™ microbubbles. The acoustic output settings were within the commonly used diagnostic ranges. Sonoporation with SonoVue® resulted in a significant decrease in weight vs. DOX alone (p = 0.0004) in the first nine days, whilst all other comparisons were not significant. Ultrasound alone resulted in a 381% increase in DOX uptake vs. DOX alone (p = 0.0004), whilst SonoVue® (p = 0.0001) and Sonazoid™ (p < 0.0001) further increased the uptake nine days after treatment (419% and 493%, respectively). No long-standing damage was observed in the kidneys via histology. In future sonoporation and drug uptake studies, we therefore suggest including an “ultrasound alone” group to verify the actual contribution of the individual components of the procedure on the drug uptake and to perform collateral damage studies to ensure there is no negative impact of low-intensity sonoporation on healthy tissues.

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Section: Study Limitations and Future Workmentioning

confidence: 99%

Ultrasound and Microbubbles Enhance Uptake of Doxorubicin in Murine Kidneys

et al. 2021

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“…Using xenograft mouse models of PDAC, Schultz et al investigated PDAC sonoporation using all four worldwide clinically-approved UCA (Optison, Definity, Lumason/SonoVue, and Sonazoid (GE Healthcare)) and two ultrasound regimens (2.0 MHz 20 ms pulses at low and high acoustic powers for 10 minutes) to identify the ideal parameters to increase therapeutic efficacy. 96 Treatment with high power ultrasound (I SPTA = 200 mW cm À2 ) utilizing Sonazoid as the UCA most consistently caused an increase in permeabilization across different experiments and markers of permeability. The results from this and other pre-clinical studies indicate that UCA weaken endothelial cell junctions, increase fenestration sizes, and can generate minute resealing pores in cells, all of which can facilitate deeper penetration of chemotherapeutic agents into the PDAC tumor.…”

Section: Materials Advances Reviewmentioning

confidence: 99%

“…The results from this and other pre-clinical studies indicate that UCA weaken endothelial cell junctions, increase fenestration sizes, and can generate minute resealing pores in cells, all of which can facilitate deeper penetration of chemotherapeutic agents into the PDAC tumor. 48,49,96 A Phase I clinical trial aimed at augmenting standard-of-care chemotherapy efficacy led to significant improvement in 10 PDAC patients receiving sonoporation treatment compared to 63 historical controls. 97,98 The results included tumor regression in 50% of the patients and a significant increase in the number of treatments patients were able to undergo (8.3 AE 6.0 cycles in controls, 13.8 AE 5.6 cycles after sonoporation treatment; p = 0.008).…”

Section: Microbubble Cavitation-based Drug Deliverymentioning

confidence: 99%

Making waves: how ultrasound-targeted drug delivery is changing pharmaceutical approaches

et al. 2022

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“…Overall, the higher power US exposure and Sonazoid were the most consistently effective, and a larger phase II clinical trial is being pursued. 117 Kotopoulis showed that compared to chemotherapy alone, US and MBs along with chemotherapy could increase the number of treatment cycles, extending the quality of life in patients. 118 The safety and efficacy of US+MBs for increasing the malignant tumors' chemotherapeutic sensitivity in the digestive system were studied.…”

Section: Interaction Of Ultrasound Withmentioning

confidence: 99%

“…Four different US contrast agents (UCAs), Definity, SonoVue, Optison, or Sonazoid and low- or high-power US exposure (60 and 200 mW/cm 2 , respectively) were tested for enhancing therapeutic efficacy. Overall, the higher power US exposure and Sonazoid were the most consistently effective, and a larger phase II clinical trial is being pursued . Kotopoulis showed that compared to chemotherapy alone, US and MBs along with chemotherapy could increase the number of treatment cycles, extending the quality of life in patients …”

Section: Interaction Of Ultrasound With Biological Systems: Physical ...mentioning

confidence: 99%

Ultrasound-Enabled Therapeutic Delivery and Regenerative Medicine: Physical and Biological Perspectives

Bansal

Jha

Bhatia

et al. 2021

ACS Biomater. Sci. Eng.

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The role of ultrasound in medicine and biological sciences is expanding rapidly beyond its use in conventional diagnostic imaging. Numerous studies have reported the effects of ultrasound on cellular and tissue physiology. Advances in instrumentation and electronics have enabled successful in vivo applications of therapeutic ultrasound. Despite path breaking advances in understanding the biophysical and biological mechanisms at both microscopic and macroscopic scales, there remain substantial gaps. With the progression of research in this area, it is important to take stock of the current understanding of the field and to highlight important areas for future work. We present herein key developments in the biological applications of ultrasound especially in the context of nanoparticle delivery, drug delivery, and regenerative medicine. We conclude with a brief perspective on the current promise, limitations, and future directions for interfacing ultrasound technology with biological systems, which could provide guidance for future investigations in this interdisciplinary area.

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Selecting the optimal parameters for sonoporation of pancreatic cancer in a pre-clinical model

Cited by 15 publications

References 41 publications

Ultrasound and Microbubbles Enhance Uptake of Doxorubicin in Murine Kidneys

Ultrasound and Microbubbles Enhance Uptake of Doxorubicin in Murine Kidneys

Making waves: how ultrasound-targeted drug delivery is changing pharmaceutical approaches

Ultrasound-Enabled Therapeutic Delivery and Regenerative Medicine: Physical and Biological Perspectives

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