Ultrasound assistance improves photothermal therapy

26 Jun 2024

DGIST project could expand the clinical applications of photothermal methods.

Turn up the heat: photothermal therapy reaches the target

A project at South Korea's Daegu Gyeongbuk Institute of Science and Technology (DGIST) has used ultrasound to enhance the effects of photothermal therapy (PTT).

Published in Advanced Optical Methods the findings could point to expanded clinical uses for PTT, which is currently applied mainly to areas of superficial tissue or treatment of local tumors due to the inherently limited penetration depth of the technique.

"Phototherapy is widely used in clinical settings for skin tightening, laser tattoo removal, and laser cancer therapy, since it can selectively improve or destroy targeted lesions," commented the GIST team.

"However, as light travels through biological tissues, optical scattering occurs, causing distortion of the light path and limiting the depth of light penetration. Against this backdrop, a fundamental problem of limited depth in light-based treatments arises."

Ways to get around this problem have involved development of photothermal agents added to the treatment area. These can be designed to absorb near-infrared wavelengths so as to transfer thermal energy to the specific spot required, or even rupture the target cells through physical action as molecular jackhammers.

But research into methods to reduce the optical scattering itself has been limited. Since 2017 DGIST has been researching whether ultrasound can offer a way to improve things, by creating micron-scale gas bubbles in organic materials with high-intensity ultrasonic waves.

These bubbles reduce optical scattering by providing a volume through which light can pass directly without refraction, essentially a variant of optical clearing methods. In 2022 DGIST used this approach to improve the depth penetration of laser scanning microscopy, increasing the imaging depth by a factor of six.

Handheld instrument eliminates melanoma

DGIST has now applied the same principle to PTT, to create ultrasound-assisted photothermal therapy (ULTRA-PTT). The gas bubbles created with ultrasound now allow the infrared radiation in PTT to be more accurately delivered to the tissues of interest, improving the efficacy of the therapy.

To make the technique suitable for clinical use, DGIST has designed a hand-held unit, or "handpiece," comprising four components: the main body with a grip for the user, the ultrasound generation unit that creates and maintains air bubbles within biological tissues, the laser irradiation unit that delivers light through a doughnut-shaped central hole on the main body, and the housing unit containing a medium for transmitting ultrasound to biological tissues.

In trials on mice with melanoma, conventional photothermal therapy displayed a reduction in tumor size for the first two days, but subsequently tumor regrowth often occurred. Treatment with the ULTRA-PTT handpiece, however, continuously reduced tumor size, leading to complete elimination after eight days.

In addition DGIST confirmed that the air bubbles generated by ultrasound energy caused no damage to biological tissues, which returned to their pre-treatment state, proving the safety of the method for future human application.

"This research allowed us to apply and expand the ultrasound-induced optical clearing technology, which we developed, to light-based therapy devices," commented DGIST's Jin-ho Chang. "The ULTRA-PTT handpiece demonstrates excellent therapeutic performance in animal experiments, and proved its safety and efficacy through histological analysis, showing the potential for commercialization of domestically developed proprietary technology."