title: Doxorubicin Delivery into Tumor Cells by Stable Cavitation without Contrast Agents.
abstract: Doxorubicin, alone or in combination with other anticancer agents, is one of the most widely used chemotherapeutic agents and is administered in a wide range of cancers. However, the use of doxorubicin is limited due to its potential serious adverse reactions. Previous studies have established the ability of high intensity focused ultrasound (HIFU) in combination with various contrast agents to increase intracellular doxorubicin delivery in a targeted and noninvasive manner. In this study, we developed a new sonoporation device generating and monitoring acoustic cavitation bubbles without any addition of contrast agents. The device was used to potentiate the delivery of active doxorubicin into both adherent and suspended cell lines. Combining doxorubicin with ultrasound resulted in a significant enhancement of doxorubicin intracellular delivery and a decrease in cell viability at 48 and 72 h, in comparison to doxorubicin alone. More importantly and unlike previous investigations, our procedure does not require the addition of contrast agents to generate acoustic cavitation and to achieve high levels of doxorubicin delivery. The successful translation of this approach for an in vivo application may allow a significant reduction in the dosage and the adverse effects of doxorubicin therapy in patients.
authors.affiliation: Université de Lyon, Université de Lyon 1 , 69000 Lyon, France.|INSERM U1052, Centre de Recherche en Cancérologie de Lyon , 69008 Lyon, France.|CNRS UMR 5286, Centre de Recherche en Cancérologie de Lyon , 69008 Lyon, France.|Hospices Civils de Lyon , Pierre Bénite, France.
authors.forename: Kamel
authors.identifier: 0000-0002-5311-3792
authors.initials: K
authors.lastname: Chettab
authors.affiliation: Université Lyon, Université Lyon 1, INSERM, LabTAU , F-69003 Lyon, France.
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Mestas
authors.affiliation: Université Lyon, Université Lyon 1, INSERM, LabTAU , F-69003 Lyon, France.
authors.forename: Maxime
authors.initials: M
authors.lastname: Lafond
authors.affiliation: Université de Lyon, Université de Lyon 1 , 69000 Lyon, France.|INSERM U1052, Centre de Recherche en Cancérologie de Lyon , 69008 Lyon, France.|CNRS UMR 5286, Centre de Recherche en Cancérologie de Lyon , 69008 Lyon, France.
authors.forename: Djamel Eddine
authors.initials: DE
authors.lastname: Saadna
authors.affiliation: Université Lyon, Université Lyon 1, INSERM, LabTAU , F-69003 Lyon, France.
authors.forename: Cyril
authors.initials: C
authors.lastname: Lafon
authors.affiliation: Université de Lyon, Université de Lyon 1 , 69000 Lyon, France.|INSERM U1052, Centre de Recherche en Cancérologie de Lyon , 69008 Lyon, France.|CNRS UMR 5286, Centre de Recherche en Cancérologie de Lyon , 69008 Lyon, France.|Hospices Civils de Lyon , Pierre Bénite, France.
authors.forename: Charles
authors.initials: C
authors.lastname: Dumontet
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003287:Contrast Media / Q000008:administration & dosage / Q000737:chemistry*; D004317:Doxorubicin / Q000008:administration & dosage* / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods; D006801:Humans; D014465:Ultrasonics / Q000379:methods; D014463:Ultrasonography / Q000379:methods
chemical_list: D000970:Antineoplastic Agents; D003287:Contrast Media; D004317:Doxorubicin
keywords: cavitation; cell death; doxorubicin