Unseeded Inertial Cavitation for Enhancing the Delivery of Chemotherapies: A Safety Study

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• 作者：Maxime Lafond^&lowast ; ; ^{maxime.lafond@inserm.fr" class="auth_mail" title="E-mail the corresponding author} ; Jean-Louis Mestas^&lowast ; ; ^&dagger ; ; Fabrice Prieur^&lowast ; ; Kamel Chettab^&Dagger ; ; Sandra Geraci^§ ; ; Philippe Clé ; zardin^§ ; ; Cyril Lafon^&lowast ; ; ^&dagger ;
• 关键词：Inertial cavitation ; Confocal ultrasound ; Metastasis ; Drug delivery ; Doxorubicin ; Ultrasound ; Safety
• 刊名：Ultrasound in Medicine & Biology
• 出版年：2016
• 出版时间：January 2016
• 年：2016
• 卷：42
• 期：1
• 页码：220-231
• 全文大小：1686 K

文摘

Acoustic cavitation can improve local drug delivery in tumors. Without injected external nucleation agents, initiating inertial cavitation requires high negative pressures, which can lead to biological damage. In the present study, unseeded inertial cavitation was obtained in vivo using confocal beams, and the effect of these exposure conditions was assessed on drug structure and activity, shallow tissues and growth of breast tumors. No change was observed in the structure and cytotoxicity of doxorubicin. Experiments were conducted on healthy rats, exposing the thigh and abdomen. Histologic analyses at 72 h and 2 weeks post-treatment demonstrated a modest impact on tissues. Syngeneic 4 T1 breast tumors in mice were sonicated. Immunohistochemical analyses showed that ultrasound did not impact vascular density, proliferation and apoptosis of cancer cells. In addition, ultrasound did not negatively modify cancer cell spreading to the lungs and bone marrow. This provides evidence that these particular parameters can be used safely in vivo.