New ULTRA-PTT technology enhances the performance of conventional photothermal therapy

Professor Jin-ho Chang's research team from the Department of Electrical Engineering and Computer Science at DGIST (President Kun-woo Lee) developed "Ultrasound-assisted photothermal therapy (ULTRA-PTT)" technology that significantly enhances the performance of conventional photothermal therapy. This technology was developed in collaboration with Senior Researcher Hye-min Kim from the Advanced Photonics Research Institute at GIST (President Ki-chul Lim) using the team's proprietary "ultrasound-induced optical clearing" technology.

Phototherapy, using light, 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. 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.

The penetration depth of light is proportional to the laser wavelength. Therefore, in clinical settings, near-infrared lasers (800-1,000nm) are used to increase light penetration depth for therapy. However, upon investigation for medical treatments, near-infrared lasers are highly absorbed by water-rich substances. The human body is composed of about 60% water, which can lead to significant energy absorption by the epidermis, resulting in side effects such as burns. Moreover, the inability to utilize wavelengths optimized for each specific disease treatment leads to increased treatment frequency and costs.

To address these issues, many researchers are conducting various studies, but the majority are focusing on developing "photothermal agents" that effectively absorb near-infrared laser wavelengths targeted at lesions. In contrast, research progress on methods to reduce optical scattering itself remains limited.

Against this backdrop, Professor Chang's team has been conducting ongoing research since 2017 to reduce optical scattering itself. They utilize air bubbles within biological tissues via ultrasound to effectively overcome limitations of light penetration depth. As a result, they developed the "ultrasound-induced optical clearing" technology, which minimizes optical scattering using a temporarily created layer of air bubbles. They applied this technology to a confocal fluorescence microscope, confirming that it enables imaging depths over six times greater than conventional methods. Their findings were published in the journal "Nature Photonics" in 2022.

Following this, the team developed "Ultrasound-assisted photothermal therapy (ULTRA-PTT)" by applying "ultrasound-induced optical clearing" technology to photothermal therapy. They created a medical device called the "handpiece" based on this technology. The "ULTRA-PTT handpiece" is designed for easy handling and comprises four components: the main body for user grip, 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.

To verify the therapeutic efficacy of this technology, the team assessed the potential clinical application of the "ULTRA-PTT handpiece" by using it on mice with melanoma, a type of skin cancer, for about eight days. Conventional photothermal therapy displayed a reduction in tumor size for the first two days, but subsequently, tumor regrowth often occurs, leading to diminished treatment efficacy. However, the therapy with the "ULTRA-PTT handpiece" continuously reduced tumor size, leading to complete elimination after eight days. Furthermore, through histological analysis, the team confirmed that air bubbles generated by ultrasound energy do not cause damage to biological tissues, and it was demonstrated that tissues return to their pre-treatment state, proving the safety of the method for human application.

This research allowed us to apply and expand the 'ultrasound-induced optical clearing' technology, which our team developed, to light-based therapy devices. Especially, 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."

Professor Jin-ho Chang of DGIST

This research was funded by the Mid-career Research Program of the National Research Foundation of Korea, and the findings of the study were published in Advanced Optical Materials (Impact Factor=9.0), one of the most renowned international journals in the field of optical science.