Nanocarrier-driven neutron capture therapy: Strategies and perspectives

Neutron capture therapy (NCT) is an emerging and highly promising cancer radiotherapy strategy that kills tumor cells by releasing high-energy particles through nuclear reactions after capturing thermal neutrons. However, the types of neutron drugs with clinical potential are currently limited and expensive, and improving the targeted accumulation of neutron drugs at tumor sites remains a key challenge. Recently, with the continuous development of nanotechnology and drug carriers, nano-neutron agents and targeted delivery systems have gradually become a research focus to enable more efficient neutron therapy. This review first systematically summarizes the types and development progress of current neutron drugs. It then focuses on the main strategies for driving neutron therapy with nanocarriers, including the development of nanodrugs enriched with neutron agents, improving the targeted accumulation and uniform distribution of neutron drugs at tumor sites, and achieving combinations of NCT with other therapies, with a discussion of the underlying mechanisms. Finally, the review deeply analyzes the major challenges in the field and potential solutions. Our work aims to drive the innovative application of nanotechnology in NCT, providing a comprehensive overview of new-generation NCT strategies based on nanocarriers. STATEMENT OF SIGNIFICANCE: This review systematically explores how nanotechnology enhances neutron capture therapy (NCT) for cancer treatment. It highlights recent advances in nano-carriers for boron, gadolinium, and lithium agents, focusing on improved tumor targeting and therapeutic efficacy. The review also discusses synergistic strategies combining NCT with immunotherapy, photothermal, and chemotherapy. By addressing current challenges and future directions, this work provides a comprehensive roadmap to guide research and clinical translation, aiming to promote more effective and precise cancer therapies.