In the segment 'A Look Around Innovation,' we introduce research and development (R&D) sites that have led to social implementation. In the 25th installment of this series, we introduce Professor Naoki Komatsu of the Graduate School of Human and Environmental Studies, Kyoto University, who is working on research that could lead to a new cancer treatment. He has developed technology that uses boron-containing nanoparticles to kill only cancer cells and has established a startup company. Its efficacy has already been confirmed in mice, and he is now aiming for clinical trials in humans.
BNCT requires long time infusion: The major burden on patients is a challenge
Displayed on the shelves in Professor Naoki Komatsu's laboratory at Kyoto University's Yoshida-South Campus are models that look like soccer balls and tubes. These are nanomaterials called fullerenes and carbon nanotubes, respectively, composed solely of carbon atoms. Komatsu, who has pursued a research career with an interest in such carbon materials, is now working on fusing nanotechnology with a cancer treatment called Boron Neutron Capture Therapy (BNCT).
BNCT itself is an existing treatment method. When thermal neutrons, which are harmless to living organisms, collide with boron, a nuclear reaction occurs, generating alpha particles and lithium nuclei (Figure 1). These destroy the DNA of cancer cells and kill them. The travel distance of alpha particles and lithium nuclei is only about the size of one cell. It is believed that if boron can be delivered only to cancer cells, the impact on other normal cells will be minimal.
BNCT has been covered by insurance for certain cancers since 2020, but there are also challenges. Current BNCT uses boronophenylalanine (BPA), in which boron is bound to an amino acid called phenylalanine. Cancer cells take up phenylalanine, and boron is delivered to cancer cells by utilizing this property. However, since this drug is a relatively small molecule with poor retention in tumors and blood, and additionally has low water solubility, patients must receive intravenous infusions for as long as three hours, placing a significant burden on them. Furthermore, because normal cells also take up phenylalanine, there is a risk that boron will accumulate in normal cells as well. Therefore, when attempting to expose cancer cells deep within the body to thermal neutrons, there is concern that normal cells will also be destroyed. For these reasons, current BNCT is only covered by insurance for head and neck cancers, including those in the nose and throat, which are near the body surface.
Results born from new encounters: The new formulation requires only one injection
Komatsu began his BNCT research after joining Kyoto University in 2015. Prior to that, he had spent about 10 years at Shiga University of Medical Science working on research into "drug delivery systems (DDS)" that use nanomaterials as carriers to deliver drugs to targeted locations within the body. Kyoto University has a nuclear reactor in the Institute for Integrated Radiation and Nuclear Science (KURNS), where BNCT research and development has been progressing for a long time. Komatsu thought that by replacing the carbon in diamond nanoparticles, which he had been handling in DDS research, with boron, large amounts of boron could be efficiently delivered to cancer cells. He began joint research with Professor Minoru Suzuki of KURNS. They developed a new formulation called "RN-501," in which nanoparticles rich in boron are coated with a polymer highly soluble in water (hydrophilic polymer) (Figure 2). Reflecting on this, Komatsu says, "This is a result born from meeting Dr. Suzuki."
While advancing the research, he received advice on social implementation from Dr. Hiroyuki Ueno of Kyoto University Innovation Capital (Kyoto iCAP), which supports entrepreneurship of Kyoto University researchers. Therefore, he applied to JST's University-Originated New Industry Creation Fund Program feasibility study and decided to conduct verification of cancer recurrence prevention capability and safety toward social implementation.
Komatsu's technology differs significantly in that while the current boron formulation (BPA) consists of molecules less than 1 nanometer in size, his formulation uses nanoparticles of 50 nanometers. Because the nanoparticles have excellent retention in cancer tissue, drug administration requires only one injection. It was also confirmed that sufficient amounts of boron had accumulated in mouse tumors two days after injection. When thermal neutrons were irradiated to these tumors, it was found that they disappeared in four out of five mice three weeks later (Figure 3). "A major characteristic is that much more boron remains in cancer tissue for a longer period compared with the current boron formulation. If we can utilize this characteristic, we may be able to treat cancers deep within the body," he says, aiming ultimately to treat lung cancer.
Furthermore, treatment using BNCT with RN-501 may not only kill existing cancers but also prevent cancer recurrence. First, after implanting tumor cells into a mouse's thigh, cancer treatment was performed by BNCT with RN-501. Then, when the tumor cells were implanted again into the other thigh of the mouse that had been cured of cancer, the implanted cancer did not grow at all. This suggests the possibility that the immune system memorized the cancer antigen. Komatsu speculates, "There may be an effect similar to a cancer vaccine, where the immune system that has memorized the cancer antigen prevents cancer recurrence."
Working on improving selectivity, visualization and aiming to elucidate the mysterious "vaccine effect"
Based on the experimental results, they judged that they could embark on full-scale research toward clinical trials using BNCT with RN-501. In April 2024, they established the startup "RadioNano Therapeutics" on the Yoshida Campus together with Drs. Masatoshi Chiba and Hiroshi Kawai, who had worked for major pharmaceutical companies for many years, and Ueno from Kyoto iCAP, aiming for clinical trials in humans and social implementation. Suzuki serves as a scientific advisory committee member, and Komatsu serves as an independent director and scientific advisory committee member. "As someone who has continued basic research, I never considered starting a business myself, but having my research results socially implemented is the greatest honor for a researcher," he commented.
In November of the same year, JST invested in the company through the Support Program of Capital Contribution to Early-Stage Companies (SUCCESS). Along with investments from other companies, they are working on improving the performance of RN-501 and adding functions, such as improving selectivity for cancer and visualization through diagnostic imaging. In April 2025, they were selected for the Japan Agency for Medical Research and Development (AMED)'s "Bridging Research Program (Seeds F)," and are attempting to further accelerate research toward implementing clinical trials.
Komatsu himself wishes to continue basic research steadily in the future. "Actually, it has been suggested that the nanoparticles may not be taken into the interior of cancer cells but remain outside the cells. I want to elucidate the detailed properties, including effects similar to vaccines," he says, discussing the prospects for his research. We hope that Komatsu's research will become a new option for future cancer treatment.
(Article: Shosuke Shimada, Photography: Hiroshi Matsui)