Researchers have cleared two major hurdles that have limited the use of minimally invasive cancer therapy, moving photo thermal treatment closer to widespread clinical adoption. This approach uses near-infrared laser light to selectively heat and destroy cancer cells. However, two specific problems have historically prevented the method from becoming a common standard of care. The first issue involves the immune system’s tendency to clear nanoparticles before they reach the tumor.
The second challenge involves the physics of light delivery, as conventional external lasers lose energy when passing through skin and tissue, making it difficult to heat deep-seated tumors effectively. The immune system frequently identifies foreign materials and triggers a rapid clearance mechanism, effectively depleting the therapeutic payload from circulation before it can accumulate at the disease site.
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Designing a Stealth Protein
To solve the nanoparticle clearance issue, the team employed AlphaFold to redesign human serum albumin (HSA). This naturally occurring blood protein helps materials avoid detection by the immune system. The researchers created a new biodegradable protein called IDP1, which is flexible and attracts water. In mice, nanoparticles coated with IDP1 remained in the bloodstream for more than four times longer than those coated with polyethylene glycol (PEG). The study noted that IDP1-coated nanoparticles accumulated efficiently in tumors while showing minimal distribution to healthy organs. The protein’s disordered structure allows it to form a hydration shell, which creates a physical barrier that hinders the binding of opsonins—proteins that tag foreign particles for destruction.
This protein design isn’t just a win for cancer therapy. The AI-based approach could be applied to improve how long many other medicines remain in the bloodstream, addressing a limitation common across many drug delivery platforms. The researchers plan to test the IDP1 platform in other types of cancer, including head and neck, esophageal, and pancreatic cancers, which can be reached using an endoscope. By extending the circulation half-life of various pharmaceutical agents, this strategy could potentially reduce the frequency of dosing required for chronic treatments.
Inside the Tumor
The second hurdle required a redesign of the laser delivery system. The team developed an ultra-thin rigid endoscope small enough to fit inside a standard 16-gauge needle. This device uses graded-index plastic optical fiber (GI-POF) lens technology. Unlike a simple modification of existing fiber-optic systems, this lens was 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 light loss that normally occurs as it passes through healthy tissue. This graded-index technology corrects for light distortion as it travels through the fiber, ensuring that the therapeutic energy is focused precisely where it is needed.
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Because the light enters the tumor directly, the system heated the cancer just as effectively as conventional treatment while using 28 percent less laser power. The study recorded 500 mW of power compared with the 700 mW typically required. The reduction in laser power also reduced damage to nearby healthy tissue. The endoscope includes a real-time fluorescence imaging system, allowing doctors to see the tumor and accurately position the device before treatment begins. This integrated imaging capability ensures that the treatment area is precisely defined, minimizing the risk of collateral damage to surrounding structures.
Results in Mice
In mice with colon cancer, a single dose of IDP1-CNH/ICG followed by one laser treatment caused 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. The researchers plan to carry out safety studies before moving toward clinical use. Details of the study were published as an invited contribution to Small Science, where Eijiro Miyako also serves on the Editorial Advisory Board. The significant duration of the study suggests that the treatment achieved durable remission, providing strong evidence for the potential of this combined therapeutic approach.
