Image-Guided Treatment of Primary Liver Cancer in Mice Leads to Vascular Disruption and Increased Drug Penetration

Frontiers in Pharmacology

Yak-Nam Wang¹  Dingjie Suo²  Sara B. Keller²  Michalakis A. Averkiou²  Heidi Kenerson³  Raymond S. Yeung³ 

[1] Applied Physics Laboratory, University of Washington, Seattle, WA, United States;Department of Bioengineering, University of Washington, Seattle, WA, United States;Department of Surgery, University of Washington, Seattle, WA, United States;

关键词: ultrasound;    drug delivery;    vascular disruption;    microbubbles;    hepatocellular carcinoma;    doxorubicin;   

DOI  :  10.3389/fphar.2020.584344

来源: DOAJ

【 摘 要 】

Despite advances in interventional procedures and chemotherapeutic drug development, hepatocellular carcinoma (HCC) is still the fourth leading cause of cancer-related deaths worldwide with a <30% 5-year survival rate. This poor prognosis can be attributed to the fact that HCC most commonly occurs in patients with pre-existing liver conditions, rendering many treatment options too aggressive. Patient survival rates could be improved by a more targeted approach. Ultrasound-induced cavitation can provide a means for overcoming traditional barriers defining drug uptake. The goal of this work was to evaluate preclinical efficacy of image-guided, cavitation-enabled drug delivery with a clinical ultrasound scanner. To this end, ultrasound conditions (unique from those used in imaging) were designed and implemented on a Philips EPIQ and S5-1 phased array probe to produced focused ultrasound for cavitation treatment. Sonovue® microbubbles which are clinically approved as an ultrasound contrast agent were used for both imaging and cavitation treatment. A genetically engineered mouse model was bred and used as a physiologically relevant preclinical analog to human HCC. It was observed that image-guided and targeted microbubble cavitation resulted in selective disruption of the tumor blood flow and enhanced doxorubicin uptake and penetration. Histology results indicate that no gross morphological damage occurred as a result of this process. The combination of these effects may be exploited to treat HCC and other challenging malignancies and could be implemented with currently available ultrasound scanners and reagents.

【 授权许可】

Unknown