New Approach

SEHS developed brand-new cyclic N-aminoluciferins (cyL) as firefly luciferase substrates with enhanced bioluminescence properties. Our results unambiguously indicated that these aminoluciferin analogues serve as effective substrates for firefly luciferase, producing robust bioluminescent signals in vitro, in cellulo, and in vivo.

What can we help?

The brain is an essential component of the central nervous system. Numerous adverse consequences will result from its destruction, including headaches, seizures, blurred vision, memory loss, nausea, vomiting, and limb weakness. Consequently, brain tumors affect a variety of physiological functions. According to certain studies, intracranial tumors account for 5% of all body malignancies and 70% of childhood tumors, while 20-30% of other malignant tumors will develop into intracranial tumors. Our study aims to provide an innovative approach to bioluminescence imaging in the medical field by the utilization of novel cyL, substantially transforming existing views on cancer progression and treatment strategies. Our team hopes that our results can contribute to brain biology and medicine, as well as to the improvement of drug design and development for brain tumors.

Our goal

Our aim is to create novel luciferin analogs that are highly sensitive and lipid-soluble, providing robust bioluminescent signals and enhanced detection sensitivity for the direct monitoring of cancer progression. This effort seeks to fulfill a persistent demand for sophisticated brain bioluminescence imaging tools in living organisms. Furthermore, we aim to decrease expenses and mitigate the impact of drug metabolism in vivo, broaden the applications of bioluminescence imaging through novel luciferin analogs, and ultimately revolutionize existing methodologies for understanding cancer progression and therapeutic options.

Results

Our research unequivocally illustrates that CyL compounds serve as valuable substrates for firefly luciferase, producing robust bioluminescent signals in both in vitro and in vivo. These compounds exhibit red-shifted bioluminescent emission, prolonged bioluminescence lifetimes, the capacity to cross the blood-brain barrier, and enhanced cell permeability, all of which are essential for tissue penetration in in vivo imaging.

In conclusion, the integration of lipophilic cyclic amine groups into aminoluciferin has resulted in the development of sensitive cyL substrates for firefly luciferase.

Among these, 7-cyL emerges as a promising candidate for bioluminescence imaging of brain tumors owing to its enhanced permeability across the blood-brain barrier. 7-cyL uniquely combines red-shifted bioluminescent emission, prolonged bioluminescence duration, enhanced blood-brain barrier penetration, and increased cell permeability. Our approach offers a significant advancement, enabling the direct study of cancer progression and addressing a long-standing gap in living animal imaging capabilities that existing tools cannot fill. We believe that these CyL compounds will expand the scope of bioluminescence imaging techniques and deepen our understanding of brain tumor progression and therapeutic strategies.