AI-Designed Protein and Needle-Based Endoscope Overcome Dual Barriers to Photothermal Cancer Therapy
Key Insights
Researchers used AlphaFold (search) to design IDP1 (search), a biodegradable protein coating that extended nanoparticle circulation time more than fourfold compared to PEG in mouse models.
An ultra-thin rigid endoscope fitting inside a 16-gauge needle delivers laser light directly into tumors, using 28% less power while maintaining efficacy.
In colon cancer (search)-bearing mice, a single dose of IDP1 (search)-coated nanoparticles plus one laser treatment eliminated tumors within 14 days with no recurrence over 40 days.
A collaborative research team led by Tohoku University has simultaneously solved two longstanding barriers that have kept photothermal cancer therapy from entering mainstream clinical use: rapid immune clearance of therapeutic nanoparticles and inefficient laser delivery to deep-seated tumors. The dual-pronged solution, published as an invited contribution to Small Science, combines an AI-designed stealth protein coating with a needle-based endoscopic laser system.
"Nanoparticle clearance and laser delivery have long stood in the way of photothermal cancer treatment but we have now overcome both challenges simultaneously," said 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. (search), Teikyo University, and Japan Advanced Institute of Science and Technology (search).
AI-Driven Protein Engineering Extends Nanoparticle Circulation
Photothermal therapy relies on near-infrared laser light to selectively heat and destroy cancer cells, but the immune system typically clears nanoparticle carriers before they can accumulate in tumors. To circumvent this, Miyako and colleagues turned to AlphaFold (search), the AI protein structure prediction tool, to redesign human serum albumin (HSA)—a naturally occurring blood protein capable of helping materials evade immune detection.
The result was IDP1 (search), a flexible, water-attracting biodegradable protein. In mice, nanoparticles coated with IDP1 remained in the bloodstream for 150.5 minutes, compared with just 17.8 minutes for those coated with polyethylene glycol (PEG), the current standard—representing more than an eightfold improvement. When loaded with carbon nanohorns (search) and the light-activated dye indocyanine green (ICG), the IDP1-coated nanoparticles accumulated efficiently in tumors while showing minimal distribution to healthy organs.
Needle-Based Endoscope Enables Internal Laser Delivery
The second challenge involved laser attenuation. Conventional external laser irradiation loses substantial energy traversing skin and overlying tissue, compromising its ability to heat deep-seated tumors. The team addressed this by developing 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. (search) The optical fiber lens was designed specifically to comply with clinical needle gauges, rather than being a modification of existing fiber-optic systems.
By inserting the endoscope directly into the tumor, the system delivers laser light internally, bypassing healthy tissue entirely. This contact-mode approach heated tumors as effectively as conventional external treatment while requiring only 500 mW of laser power—a 28% reduction compared with the 700 mW needed for external irradiation. The lower power also reduced collateral damage to adjacent healthy tissue. The endoscope further incorporates a real-time fluorescence imaging system, enabling clinicians to visualize the tumor and precisely position the device before treatment.
Preclinical Efficacy and Future Directions
In mice bearing colon cancer (search), a single dose of IDP1 (search)-CNH/ICG followed by one laser treatment caused tumors to disappear completely within 14 days. No tumor recurrence was observed during the 40-day study period, and researchers detected no signs of harmful side effects.
Beyond oncology, the AI-based protein design approach used to create IDP1 (search) could be applied to extend the bloodstream residence time of numerous other medicines. The contact-mode endoscope system may also prove useful for treating other tumor types accessible by needle.
The research team plans to conduct safety studies before advancing toward clinical use. They will also evaluate the IDP1 (search) platform in additional cancer types, including head and neck, esophageal, and pancreatic cancers—all of which can be reached using an endoscopic approach.