Ultrasonic Microbubble Cavitation Enhanced Tissue Permeability and Drug Diffusion in Solid Tumor Therapy

He, Jide; Liu, Zenan; Zhu, Xuehua; Lu, Jian

doi:10.3390/pharmaceutics14081642

Cited by 22 publications

(11 citation statements)

References 118 publications

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“…Therefore, MB dosing schedule and impact of MB size should be revisited (Choi et al 2010, McMahon and. Studies have shown that liposomes with particles sizes from 100 to 200 nm can accumulate agent concentration four times greater than particles sizes smaller than 50 nm or larger than 300 nm in tumors following low-intensity FUS (He et al 2022). It was intimated that larger MBs have a higher likelihood to increase permeability in the microvascular network (e.g.…”

Section: Discussionmentioning

confidence: 99%

Image-guided focused ultrasound-mediated molecular delivery to breast cancer in an animal model

Margolis

Basavarajappa

et al. 2023

Phys. Med. Biol.

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Tumors become inoperable due to their size or location, making neoadjuvant chemotherapy the primary treatment. However, target tissue accumulation of anticancer agents is limited by the physical barriers of the tumor microenvironment. Low-intensity focused ultrasound (FUS) in combination with microbubble (MB) contrast agents can increase microvascular permeability and improve drug delivery to the target tissue after systemic administration. The goal of this research was to investigate image-guided FUS-mediated molecular delivery in volume space. 3-D FUS therapy functionality was implemented on a programmable ultrasound (US) scanner (Vantage 256, Verasonics Inc) equipped with a linear array for image guidance and a 128-element therapy transducer (HIFUPlex-06, Sonic Concepts). FUS treatment was performed on breast cancer-bearing female mice (N = 25). Animals were randomly divided into three groups, namely, 3-D FUS therapy, 2-D FUS therapy, or sham (control) therapy. Immediately prior to the application of FUS therapy, animals received a slow bolus injection of MBs (Definity, Lantheus Medical Imaging Inc) and near-infrared dye (IR-780, surrogate drug) for optical reporting and quantification of molecular delivery. Dye accumulation was monitored via in vivo optical imaging at 0, 1, 24, and 48 h (Pearl Trilogy, LI-COR). Following the 48-h time point, animals were humanely euthanized and tumors excised for ex vivo analyses. Optical imaging results revealed that 3-D FUS therapy improved delivery of the IR-780 dye by 66.4 and 168.1% at 48 h compared to 2-D FUS (p = 0.18) and sham (p = 0.047) therapeutic strategies, respectively. Ex vivo analysis revealed similar trends. Overall, 3-D FUS therapy can improve accumulation of a surrogate drug throughout the entire target tumor burden after systemic administration.

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Section: Discussionmentioning

confidence: 99%

Image-guided focused ultrasound-mediated molecular delivery to breast cancer in an animal model

Margolis

Basavarajappa

et al. 2023

Phys. Med. Biol.

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“…[46,47] The ultrasonic microbubble cavitation effect is a process that microbubbles expand, contract, oscillate and collapse violently under sonication by ultrasound with a frequency close to the resonant frequency of the microbubble. [48,49] Microbubble cavitation produces high pressures and temperatures, and microjet induced by the rapid release of instantaneous ultrasonic energy intervened in microbubbles, [50] which leads to cellular damage or hemorrhage in biological tissues. [51] .…”

Section: Working Mechanism Of Microbubble Cavitationmentioning

confidence: 99%

Surface Acoustic Wave (SAW)‐Based Sonoporation of Single‐Adherent‐Cell

Wang,

Tian,

et al. 2023

Adv Materials Technologies

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Sonoporation refers to the formation of tiny transient pores in cell plasma membranes by using ultrasound to increase the permeability to bioactive materials. Recently, the Sonoporation technique has been widely researched in cell treatment applications, such as gene transfection. However, due to the random distribution of microbubbles, it is challenging to perform controllable and precise localized sonoporation of a target cell. In this work, a device based on the surface acoustic wave is developed to achieve a selective manipulation and cavitation of microbubbles. The device consists of a pair of microbubble positioning slant‐finger interdigital transducers (SFITs) for moving a selected microbubble in a two‐dimensional plane. Meanwhile, another narrow‐frequency‐band SFIT is integrated into the device for local cavitation control of the same microbubble. As a result, a microbubble can be transported orthogonal to and along the acoustic transmission path by continuously adjusting the input frequency and relative phase. Upon reaching the target cell, the selected microbubble can be cavitated without exciting other microbubbles, resulting in local sonoporation. The resolution of phase‐based positioning and frequency‐based transportation are 8.3 and 7.0 µm with 45° and 10 kHz settings, respectively.

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“…These biological effects lead to enhanced cellular delivery through mechanisms such as drug convection and diffusion through the pores (4-70 kDa) and endocytosis (70-500 kDa) [33][34][35]38]. Following their clinical translation as ultrasound imaging contrast agents, MB formulations have been engineered as ultrasound-responsive carriers to promote and enhance the local delivery and uptake of a wide variety of drugs [8][9][10][11], genes [12][13][14], and cells [15][16][17][18][19][20] for various therapeutic applications. Many of these applications include the delivery of therapeutic agents to treat the brain [19][20][21][22][23], heart [15,[24][25][26], and cancer [27][28][29].…”

Section: Introductionmentioning

confidence: 99%

Targeted Microbubbles for Drug, Gene, and Cell Delivery in Therapy and Immunotherapy

Navarro-Becerra

Borden

2023

Pharmaceutics

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Microbubbles are 1–10 μm diameter gas-filled acoustically-active particles, typically stabilized by a phospholipid monolayer shell. Microbubbles can be engineered through bioconjugation of a ligand, drug and/or cell. Since their inception a few decades ago, several targeted microbubble (tMB) formulations have been developed as ultrasound imaging probes and ultrasound-responsive carriers to promote the local delivery and uptake of a wide variety of drugs, genes, and cells in different therapeutic applications. The aim of this review is to summarize the state-of-the-art of current tMB formulations and their ultrasound-targeted delivery applications. We provide an overview of different carriers used to increase drug loading capacity and different targeting strategies that can be used to enhance local delivery, potentiate therapeutic efficacy, and minimize side effects. Additionally, future directions are proposed to improve the tMB performance in diagnostic and therapeutic applications.

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Ultrasonic Microbubble Cavitation Enhanced Tissue Permeability and Drug Diffusion in Solid Tumor Therapy

Cited by 22 publications

References 118 publications

Image-guided focused ultrasound-mediated molecular delivery to breast cancer in an animal model

Image-guided focused ultrasound-mediated molecular delivery to breast cancer in an animal model

Surface Acoustic Wave (SAW)‐Based Sonoporation of Single‐Adherent‐Cell

Targeted Microbubbles for Drug, Gene, and Cell Delivery in Therapy and Immunotherapy

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