Tumor ablation using low-intensity ultrasound and sound excitable drug

• Published in: Journal of controlled release Vol. 258; pp. 67 - 72
• Main Authors: Tung, Ching-Hsuan, Han, Myung Shin, Kim, Young, Qi, Jianjun, O'Neill, Brian E.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 28.07.2017
• Subjects: Animals; Antineoplastic Agents - chemistry; Antineoplastic Agents - therapeutic use; Breast Neoplasms - pathology; Breast Neoplasms - therapy; Cell Line, Tumor; Combined Modality Therapy - methods; Female; Humans; Mice; Mice, Inbred BALB C; Mice, Nude; Plasma membrane; Rose Bengal - analogs & derivatives; Rose Bengal - therapeutic use; Rupture; Sonodynamic therapy; Tumor ablation; Ultrasonic Therapy - methods; Ultrasound; Xanthenes - chemistry; Xanthenes - therapeutic use; Ultrasound; Sonodynamic therapy; Plasma membrane; Rupture; Tumor ablation
• ISSN: 0168-3659; 1873-4995
• DOI: 10.1016/j.jconrel.2017.05.009

The cell membrane is a semi-fluid container that defines the boundary of cells, and provides an enclosed environment for vital biological processes. A sound excitable drug (SED) that is non-cytotoxic to cells is developed to disrupt the plasma membrane under gentle ultrasound insonation, 1MHz, 1W/cm2. The frequency and power density of insonation are within the physical therapy and medical imaging windows; thus the applied ultrasound is safe and not harmful to tissues. The insertion of SEDs into the plasma membrane is not toxic to cells; however, the intruding SEDs weaken the membrane's integrity. Under insonation, the ultrasound energy destabilized the SED disrupted membranes, resulting in membrane rupture and eventual cell death. In a xenograft breast tumor model, the SED alone or the ultrasound alone caused little adverse effects to tumor tissue, while the combined treatment triggered necrosis with a brief local insonation of 3min. The described sono-membrane rupture therapy could be a safe alternative to the currently used high-energy tissue ablation technology, which uses X-rays, gamma rays, electron beams, protons, or high-intensity focused ultrasound. [Display omitted]