Targeted Ultrasound-Mediated Delivery of Nanoparticles: On the Development of a New HIFU-Based Therapy and Imaging Device

• Published in: IEEE transactions on biomedical engineering Vol. 57; no. 1; pp. 61 - 70
• Main Authors: Seip $^{}$, Ralf, Chin, Chien Ting, Hall, Christopher S., Raju, Balasundar I., Ghanem, Alexander, Tiemann, Klaus
• Format: Journal Article
• Language: English
• Published: United States IEEE 01.01.2010; The Institute of Electrical and Electronics Engineers, Inc. (IEEE)
• Subjects: Acoustic imaging; Animals; Annular array; Application software; Cardiology; delivery system; Drug Delivery Systems - instrumentation; Drug Delivery Systems - methods; Drugs; Echocardiography; Image Processing, Computer-Assisted - instrumentation; Image Processing, Computer-Assisted - methods; Medical treatment; Mice; Mice, Inbred C57BL; Nanoparticles; Nanoparticles - administration & dosage; noninvasive; Probes; Rats; Rats, Wistar; Software; Stem cells; therapeutic ultrasound; Ultra wideband technology; Ultrasonic imaging; Ultrasonography - instrumentation; Ultrasonography - methods; ultrasound image guidance
• ISSN: 0018-9294; 1558-2531
• DOI: 10.1109/TBME.2009.2028874

Ultrasound-mediated delivery (USMD) is an active research topic, as researchers develop applications for therapeutic ultrasound in addition to thermal ablation. In USMD, ultrasound is used in conjunction with microbubbles and drugs, nanoparticles, siRNA, pDNA, stem cells, etc., to facilitate their cellular delivery and uptake using pressure and temperature-mediated mechanisms to bring about a desired therapeutic effect. To investigate the potential of targeted USMD of nanoparticles, pDNA, and stem cells for cardiovascular and other applications, a general-purpose preclinical research tool, therapy imaging probe system (TIPS) was designed. It consists of a wideband annular array, a small-animal acoustic coupler, a motorized positioning system, integrated control software for ultrasound image-guided treatment planning and execution, and triggering electronics that allow ECG and respiration-gated ultrasound exposures. TIPS was then used to enhance delivery of nanoparticles into the murine myocardium and heart vessel walls to demonstrate the feasibility of the technology, pave the way for additional basic research in cardiovascular USMD, and begin to explore the requirements that USMD devices will have to meet to be useful in a clinical setting.