In a promising development for cancer treatment, a collaborative research team has overcome two issues that have prevented photo thermal therapy, a much less invasive treatment option than surgery and/or radiation, from becoming more common.

Photothermal therapy uses near-infrared laser light to selectively heat and destroy cancer cells. However, when the immune system senses the nanoparticles carrying therapeutic agents it often begins clearing them before they can reach the tumors. A second problem with photo thermal therapy lies in the technology itself. Conventional external laser irradiation loses energy as it passes through overlying skin and tissue, making it difficult to heat deep-seated tumors effectively.

"Nanoparticle clearance and laser delivery have long stood in the way of photothermal cancer treatment but we have now overcome both challenges simultaneously," says Eijiro Miyako, a professor at Tohoku University's Institute of Multidisciplinary Research for Advanced Materials who led the study in collaboration with Air Water Inc., Teikyo University, and Japan Advanced Institute of Science and Technology.

To address nanoparticle clearance, Miyako and his colleagues employed the AI protein structure prediction tool AlphaFold to redesign human serum albumin (HSA), a naturally occurring blood protein that can help materials avoid detection by the immune system. They created a new biodegradable protein called IDP1, which is flexible and attracts water. In mice, nanoparticles coated with IDP1 stayed in the bloodstream for more than four times longer than those coated with the commonly used material polyethylene glycol (PEG) (150.5 minutes compared with 17.8 minutes). When loaded with carbon nanohorns and the light-activated dye indocyanine green, the IDP1-coated nanoparticles accumulated efficiently in tumors while showing minimal distribution to healthy organs.

The research team then had to address the laser delivery system. To overcome this obstacle, the team developed an ultra-thin rigid endoscope - small enough to fit inside a standard 16-gauge needle - using graded-index plastic optical fiber (GI-POF) lens technology pioneered by Air Water Inc. The optical fiber lens was not merely a modification of existing fiber-optic systems but designed specifically to comply with clinical needle gauges.

By placing the endoscope directly into the tumor, the system delivers laser light from the inside, avoiding the loss of light that normally occurs as it passes through healthy tissue. This approach heated tumors just as effectively as conventional treatment while using 28% less laser power (500 mW compared with 700 mW). Because less laser power was needed, it also reduced damage to nearby healthy tissue. The endoscope also includes a real-time fluorescence imaging system, allowing doctors to see the tumor and accurately position the device before treatment.

In mice with colon cancer, a single dose of IDP1-CNH/ICG followed by one laser treatment caused the tumors to disappear completely within 14 days. The tumors did not return during the 40-day study, and the researchers found no signs of harmful side effects. Beyond cancer treatment, the AI-based approach used to design IDP1 could be applied to improve how long many other medicines remain in the bloodstream. The contact-mode endoscope system could also be used to treat other types of tumors that can be reached with a needle.

Looking ahead, the researchers plan to carry out safety studies before moving toward clinical use. They will also test the IDP1 platform in other types of cancer, including head and neck, esophageal, and pancreatic cancers, which can be reached using an endoscope.

Details of the study were published as an invited contribution to Small Science, where Miyako also serves on the Editorial Advisory Board.