Since bubbles oscillate, cavitate, and be destroyed during US stimulation, the adjacent cells might get damaged, resulting in changes to the membrane permeability or death from irreversible damage. The combination therapy of drug release and physical treatment for vascular disruption induced by bubble cavitation or acoustic droplet vaporization (ADV) improves the efficacy of tumor growth inhibition. Therapeutic ultrasound (US) combined with drug-loaded microbubbles (MBs) or acoustic droplets is extensively applied in tumor therapy. As a result, the treatment of poorly perfused regions within solid tumors is a critical issue for tumor therapy. Poorly perfused tumor regions have non-uniform intratumoral drug distribution, which reduces the therapeutic efficacy incomplete treatment of tumor cells might increase the probability of treatment resistance, malignant progression, recurrence, locoregional spread, and distant metastasis. Moreover, with chemotherapy, anti-cancer drugs are delivered to the target lesions by blood perfusion, and the penetration distance from vessels to tumor tissue is restricted by the size of the drugs and various tumor microenvironments. Since the rate of tumor cell proliferation is faster than that of angiogenesis, tumors have poorly perfused regions where there is hypoxia or necrosis due to insufficient oxygen and nutrition transport. The limited diffusion distance of oxygen is approximately 200 µm.
Introductionīlood perfusion within tumors is an important source of oxygen and nutrition transport for assisting cell proliferation. Keywords: nanodroplets, intertissue bubbles, acoustic droplet vaporization, poorly perfused regions, bubble cavitation. ADV-B formation, movement and cavitation could induce cell membrane damage by mechanical force providing a mechanism to overcome treatment limitations in poorly perfused regions of tumors. The intratumoral nanodroplet or ADV-B distribution around the poorly perfused regions with tumor necrosis or hypoxia were demonstrated by histological assessment. The poorly perfused regions within solid tumors show enhancement due to ADV-B accumulation after application of US-triggered ADV-B. When ADV-Bs were applied to tumor cells, the cell membrane was damaged, increasing cellular permeability or inducing cell death.
Intravital imaging revealed intertissue ADV-B formation, movement, and cavitation triggered by US, where the distance of intertissue ADV-B movement was 33-99 µm per pulse. In this study, we investigated the in vivo behavior of ADV-Bs stimulated by US, and evaluated the possibility of moving intertissue ADV-Bs into the poorly perfused regions of solid tumors. Acoustic droplet vaporization (ADV) has been applied to directly disrupt vessels and release nanodroplets, ADV-generated bubbles (ADV-Bs), and drugs into tumor tissue. Solid tumors with poorly perfused regions reveal some of the treatment limitations that restrict drug delivery and therapeutic efficacy. Select the file that you have just downloaded and select import option Reference Manager (RIS).
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Available fromĬlick on Go to download the file. Theranostic Performance of Acoustic Nanodroplet Vaporization-Generated Bubbles in Tumor Intertissue.
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