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New photothermal therapy overcomes major cancer treatment barriers

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 thera

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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.

Nishida, K., et al. (2026). Intrinsically Disordered Polypeptides‐Based Stealth Materials Enable Enhanced Photothermal Cancer Therapy Using an In Situ Fiber‐Based Penetrating Laser System. Small Science. DOI: 10.1002/smsc.70342. https://onlinelibrary.wiley.com/doi/full/10.1002/smsc.70342

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Related questions

01Can your research on D-amino acids be adopted by the pharmaceutical industry to develop drugs and therapies for human disease?

Absolutely it can, and in at least two ways. Firstly, as the oncometabolites that we have been discussing, as an early warning indicator for cancer. Secondly, by interfering with cancer cell D-amino acid production. We think that cancer cells actually produce D-amino acids to protect themselves against certain cancer drugs. So they are fighting back and they can do this in a matter of minutes to hours. Nobody realized this before but, knowing this, we can develop drugs to interfere with D-amino acid production by cancer cells. This will make other cancer drugs more effective.

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02What are the Applications of Affimers?

Affimers can be combined with traditional biological tests to increase our understanding of proteins. For example, affimers have been used in affinity assays, among others. They have also been used in biosensors and in cell cultures to manipulate cell signaling. Affimers have been successfully applied both in vitro and in vivo. Some of the applications that have been tested using affimers include cell imaging, super resolution microscopy, protein function modulation, magnetic nanoparticle formation, and MRI reagent development. Affimers with enhanced specificity for tubulin have been used in super resolution microscopy with high success, and can target regions of the tubulin structure that antibodies are typically restricted from. It is likely that more applications will be discovered in the future as the use of affimers becomes more widespread. For example, thanks to growing libraries of affimers, it has been possible to create affinity microarrays to discover biomarkers and potential pharmaceuticals. By finding biomarkers, affimers have been applied to cancer studies, where they have been used to target a protein in tumor vessel formation called the VEGF receptor.

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03Collaboration has played a significant role in your research career. Can you highlight some of the most impactful collaborations you've had and how they have contributed to your research in axon biology?

A significant collaboration is with the Versus Arthritis Pain Center in Nottingham, in particular with Vicky Chapman and Gareth Hathway. Initially, my work wasn't focused on pain research, but joining forces with experts from this center led half of my lab's work to be directed towards pain-related projects. Another meaningful collaboration involves studying motor neuron diseases alongside Prof. Rob Layfield and Dr. Dan Scott. This collaboration allows us to leverage our expertise in RNA and neuron development and apply it to conditions like motor neuron disease.

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04There is considerable excitement around AI in drug development. Where do you see the largest gap between hype and reality, and where is AI perhaps underappreciated?

AI is moving so quickly that in the gap between answering this and publication, I could be proved wrong! With that caveat, there is a lot of hype around AI drug discovery campaigns. AI is certainly a substantial part of many discovery programs today and has been applied in drug discovery for many years. However, we need to be realistic about what AI is doing, where humans remain central, and how that balance may vary. AI agents are an area that has emerged relatively recently and continues to evolve quickly. They can complete tasks for example data extraction and reporting with guidance from experts, helping to generate larger, more standardized datasets over time. They can also help build closed-loop systems that connect computation and experiment directly, with strategic direction still coming from expert scientists. However, care and oversight is needed with these systems to validate their actions. I also think people often equate AI with generative AI, but there are many other AI systems which are underappreciated. For example, the GNN property prediction models and task-specific predictive tools we discussed earlier can be extremely valuable. Some of these methods receive less attention simply because they have already become familiar in drug discovery.

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05What are the basic motifs of proteins?

The simplest motifs are composed of multiple secondary structure units. These simple motifs can contain α-helices and β-sheets that are layered adjacent to one another either in the same direction (parallel) or in the opposite direction (anti-parallel). The simplest motif is the formation of a “loop”, known as a β-turn if it is short, while an unstructured connection is termed a “coiled region”.

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Peptide Therapy Guide Editorial Team

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