title: Unseeded Inertial Cavitation for Enhancing the Delivery of Chemotherapies: A Safety Study.
abstract: 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.
authors.affiliation: Inserm, U1032, LabTAU, Lyon, F-69003, France; Université de Lyon, Lyon, F-69003, France. Electronic address: maxime.lafond@inserm.fr.
authors.forename: Maxime
authors.initials: M
authors.lastname: Lafond
authors.affiliation: Inserm, U1032, LabTAU, Lyon, F-69003, France; Université de Lyon, Lyon, F-69003, France; Caviskills SAS, Vaulx-En-Velin, F-69120, France.
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Mestas
authors.affiliation: Inserm, U1032, LabTAU, Lyon, F-69003, France; Université de Lyon, Lyon, F-69003, France.
authors.forename: Fabrice
authors.initials: F
authors.lastname: Prieur
authors.affiliation: Inserm, U1052, Centre de Recherche de Cancérologie de Lyon, Lyon, F-69003, France.
authors.forename: Kamel
authors.initials: K
authors.lastname: Chettab
authors.affiliation: Inserm, U1033, Lyon, F-69003, France; UFR de Médecine Lyon-Est, Lyon, F-69372, France.
authors.forename: Sandra
authors.initials: S
authors.lastname: Geraci
authors.affiliation: Inserm, U1033, Lyon, F-69003, France; UFR de Médecine Lyon-Est, Lyon, F-69372, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Clézardin
authors.affiliation: Inserm, U1032, LabTAU, Lyon, F-69003, France; Université de Lyon, Lyon, F-69003, France; Caviskills SAS, Vaulx-En-Velin, F-69120, France.
authors.forename: Cyril
authors.initials: C
authors.lastname: Lafon
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage*; D001943:Breast Neoplasms / Q000188:drug therapy*; D004195:Disease Models, Animal; D004317:Doxorubicin / Q000008:administration & dosage*; D016503:Drug Delivery Systems / Q000009:adverse effects* / Q000379:methods*; D005260:Female; D008807:Mice, Inbred BALB C; D051381:Rats; D014465:Ultrasonics / Q000379:methods*
chemical_list: D000903:Antibiotics, Antineoplastic; D004317:Doxorubicin
keywords: Confocal ultrasound; Doxorubicin; Drug delivery; Inertial cavitation; Metastasis; Safety; Ultrasound