Periodic Reporting for period 1 - TARLIT (Targeted nanohorns for lithium neutron capture therapy)
Reporting period: 2023-01-01 to 2024-12-31
Cancer remains one of the most significant global health challenges, responsible for millions of deaths each year. Among the various treatment options available, radiation therapy is used in about half of all cancer cases. However, conventional radiation treatments, such as external beam radiotherapy, often damage surrounding healthy tissues, leading to severe side effects and limiting their effectiveness, especially for tumors located near critical structures.
Neutron Capture Therapy (NCT) is a form of radiotherapy that uses specific isotopes to selectively destroy cancer cells. When these isotopes react with neutrons, they trigger a nuclear reaction that produces lethal particles, effectively killing cancer at the cellular level while minimizing damage to surrounding healthy tissues. This makes NCT particularly valuable for treating complex, recurrent, and radioresistant tumors. Although its potential was demonstrated over 50 years ago, technological advancements in neutron accelerators are only now making NCT more widely accessible. However, its clinical success is still limited by the availability of effective delivery agents that allow the accumulation of sufficient neutron-active elements at tumor sites.
TARLIT focuses on a previously unexplored approach that consists on the encapsulation of lithium-6 (6Li) compounds inside nanoparticles. In this way, leakage of lithium is prevented while the use of targeted nanoparticles enhances accumulation of the active element (6Li) into cancer cells. Despite 6Li holds great potential for NCT, most lithium salts are highly soluble, making it difficult to control their biodistribution and ensure selective tumor accumulation. Our strategy enables the targeted accumulation of lithium-6 in hard to treat tumors, such as head and neck cancer.
Neutron Capture Therapy (NCT) is a form of radiotherapy that uses specific isotopes to selectively destroy cancer cells. When these isotopes react with neutrons, they trigger a nuclear reaction that produces lethal particles, effectively killing cancer at the cellular level while minimizing damage to surrounding healthy tissues. This makes NCT particularly valuable for treating complex, recurrent, and radioresistant tumors. Although its potential was demonstrated over 50 years ago, technological advancements in neutron accelerators are only now making NCT more widely accessible. However, its clinical success is still limited by the availability of effective delivery agents that allow the accumulation of sufficient neutron-active elements at tumor sites.
TARLIT focuses on a previously unexplored approach that consists on the encapsulation of lithium-6 (6Li) compounds inside nanoparticles. In this way, leakage of lithium is prevented while the use of targeted nanoparticles enhances accumulation of the active element (6Li) into cancer cells. Despite 6Li holds great potential for NCT, most lithium salts are highly soluble, making it difficult to control their biodistribution and ensure selective tumor accumulation. Our strategy enables the targeted accumulation of lithium-6 in hard to treat tumors, such as head and neck cancer.
We employed carbon nanohorns capable of encapsulating lithium-6 compounds, preventing leakage. These nanoparticles were further modified with biocompatible coatings and tumor-targeting moieties, allowing them to selectively accumulate in cancerous cells.
Preclinical studies have been a crucial part of TARLIT’s work, providing key insights into the nanoparticles' biological behavior. In vitro experiments confirmed that the lithium-loaded nanoparticles presented no-cytotoxicity and cell internalization. In vivo studies also revealed lack of toxicity and targeted accumulation in tumor.
A major milestone in the project was testing the nanoparticles under neutron irradiation. When exposed to neutrons, the lithium-6 inside the nanoparticles underwent a nuclear reaction, releasing high-energy particles capable of destroying cancer cells. The results showed a significant reduction in cell viability, reinforcing the potential of lithium-6 as a highly effective agent for NCT. The project’s findings open the door to further development and potential commercialization.
By demonstrating the feasibility of a targeted, lithium-based NCT approach, TARLIT has laid the foundation for a new generation of nanoparticles for cancer treatment. This work has the potential to enhance the outcomes of radiation therapy. With its promising results, the project sets the stage for future preclinical studies, moving one step closer to making this innovative therapy a reality.
Preclinical studies have been a crucial part of TARLIT’s work, providing key insights into the nanoparticles' biological behavior. In vitro experiments confirmed that the lithium-loaded nanoparticles presented no-cytotoxicity and cell internalization. In vivo studies also revealed lack of toxicity and targeted accumulation in tumor.
A major milestone in the project was testing the nanoparticles under neutron irradiation. When exposed to neutrons, the lithium-6 inside the nanoparticles underwent a nuclear reaction, releasing high-energy particles capable of destroying cancer cells. The results showed a significant reduction in cell viability, reinforcing the potential of lithium-6 as a highly effective agent for NCT. The project’s findings open the door to further development and potential commercialization.
By demonstrating the feasibility of a targeted, lithium-based NCT approach, TARLIT has laid the foundation for a new generation of nanoparticles for cancer treatment. This work has the potential to enhance the outcomes of radiation therapy. With its promising results, the project sets the stage for future preclinical studies, moving one step closer to making this innovative therapy a reality.
The TARLIT project has advanced in the development of nanoparticles for lithium neutron capture therapy. Unlike conventional NCT, which mainly relies on boron-10 compounds, TARLIT has developed a unique carbon nanohorn-based delivery system that securely encapsulates lithium-6, preventing leakage and ensuring targeted accumulation in cancer cells. This highly stable design represents a major step beyond the current state of the art for treating aggressive, radioresistant cancers such as head and neck tumors.
One of the project’s key breakthroughs has been providing further evidence of the therapeutic potential of lithium-6 for neutron capture therapy. By refining the delivery system with biocompatible coatings and tumor-targeting molecules, TARLIT has significantly improved the selectivity and accumulation of the nanoparticles into cancer cells, addressing one of the main limitations of traditional NCT. Preclinical studies have confirmed the safety, stability, and efficacy of this approach, laying the foundation for further development.
To ensure the successful transition of this technology from research to the clinical setting, several key steps must be taken. Further preclinical studies will be essential to strengthen the data on long-term safety and therapeutic benefits. Additionally, the synthesis process must be standardized under Good Manufacturing Practice (GMP) conditions, ensuring that the nanoparticles can be produced at a scale suitable for clinical use.
A Freedom to Operate (FTO) analysis has confirmed that there are no intellectual property barriers preventing commercialization of the technology. This provides a strong competitive advantage and opens pathways for further industry collaborations and investment opportunities. The project team has already engaged with key companies and leading hospitals in the field of radiation oncology to explore clinical translation and commercialization strategies. These partnerships will be instrumental in advancing the development of lithium-6-based NCT and securing regulatory approvals from bodies such as the EMA and FDA.
Moving forward, the focus will be on scaling up production, conducting preclinical trials under good laboratory practices, and working closely with regulatory agencies to bring this innovation closer to clinical application.
One of the project’s key breakthroughs has been providing further evidence of the therapeutic potential of lithium-6 for neutron capture therapy. By refining the delivery system with biocompatible coatings and tumor-targeting molecules, TARLIT has significantly improved the selectivity and accumulation of the nanoparticles into cancer cells, addressing one of the main limitations of traditional NCT. Preclinical studies have confirmed the safety, stability, and efficacy of this approach, laying the foundation for further development.
To ensure the successful transition of this technology from research to the clinical setting, several key steps must be taken. Further preclinical studies will be essential to strengthen the data on long-term safety and therapeutic benefits. Additionally, the synthesis process must be standardized under Good Manufacturing Practice (GMP) conditions, ensuring that the nanoparticles can be produced at a scale suitable for clinical use.
A Freedom to Operate (FTO) analysis has confirmed that there are no intellectual property barriers preventing commercialization of the technology. This provides a strong competitive advantage and opens pathways for further industry collaborations and investment opportunities. The project team has already engaged with key companies and leading hospitals in the field of radiation oncology to explore clinical translation and commercialization strategies. These partnerships will be instrumental in advancing the development of lithium-6-based NCT and securing regulatory approvals from bodies such as the EMA and FDA.
Moving forward, the focus will be on scaling up production, conducting preclinical trials under good laboratory practices, and working closely with regulatory agencies to bring this innovation closer to clinical application.