Speaker
Description
Gil Gonçalves1,2
1Centre for Mechanical Technology and Automation (TEMA), Mechanical Engineering Department, University of Aveiro, 3810-193 Aveiro, Portugal;
2Intelligent Systems Associate Laboratory, 4800-058 Guimarães, Portugal
Cancer remains one of the leading causes of mortality worldwide, particularly in aggressive and therapy-resistant tumors, underscoring the urgent need for more selective and effective therapeutic strategies. Neutron Capture Therapy (NCT) is an advanced binary radiotherapeutic modality based on neutron capture reactions of specific isotopes that generate high linear energy transfer (LET) particles capable of selectively destroying cancer cells. To date, clinical NCT has relied primarily on ^10B-containing agents such as boronophenylalanine (BPA) and sodium borocaptate (BSH). However, these compounds exhibit significant limitations, including suboptimal tumor selectivity, heterogeneous intratumoral distribution, rapid systemic clearance, and the need for high systemic doses to achieve therapeutic boron concentrations, thereby restricting clinical efficacy.
Here, we introduce 6Li as a novel neutron-active therapeutic agent, establishing the foundation for Lithium Neutron Cancer Therapy (LiNCT).[1] Upon thermal neutron irradiation, the 6Li reaction generates highly energetic particles with high LET and short path lengths, enabling highly localized energy deposition at the cellular scale and offering strong potential to address tumor heterogeneity.
Compared with 10B-based systems, 6Li presents several conceptual and practical advantages, including a distinct nuclear reaction pathway with favorable energy partitioning, simplified chemical speciation that facilitates stable incorporation into nanocarriers, and reduced reliance on complex boron-rich molecular architectures. In addition, 6Li enables the achievement of high intracellular payload concentrations through controlled nanoencapsulation rather than systemic overexposure. Importantly, lithium compounds can be fully confined within sealed nanocapsules, thereby minimizing premature leakage and off-target toxicity, which are intrinsic limitations of many small-molecule boron agents.[2]
To enable safe and efficient intracellular delivery, we develop biomimetic nanocapsules fabricated via microfluidic technology, allowing precise control over size, surface chemistry, isotope loading, and release kinetics.[3] This strategy ensures reproducibility, scalability, and GMP compatibility. Furthermore, to address the multidimensional design space governing colloidal stability, neutron capture efficiency, and biological targeting, we integrate a closed-loop, machine-learning-guided optimization framework for rational nanoparticle engineering.
This integrated nanotechnology and data-driven platform positions LiNCT as a promising next-generation alternative to conventional boron-based NCT, paving the way toward improved selectivity, safety, and therapeutic performance.
References
[1] G. Gonçalves Lithium filled nanocapsules and use thereof WO2023180615A1
[2] G. Gonçalves et al. Lithium halide filled carbon nanocapsules: Paving the way towards lithium neutron capture therapy (LiNCT), Carbon 208 (2023)
[3] G. Gonçalves et al., Advances in Microfluidic-Based Core@Shell Nanoparticles Fabrication for Cancer Applications, Adv. Healthc. Mater. 13 (2024)
Acknowledgements
This work is funded by FCT, under UID/00481 – TEMA and the project CarboNCT 2022.03596.PTDC (DOI: 10.54499/2022.03596.PTDC).
| Track | Deployment of Nuclear Medicine in LMICs: Enabling Technologies |
|---|---|
| Presentation type | Oral |