From its inception, InDy pursued a high-risk, high-gain research strategy integrating molecular design, synthesis, photophysical characterization, and biological evaluation. Early work focused on establishing the project's technical foundations, including computationally guided design, new synthetic routes for low-molecular-weight fluorophores, and experimental workflows that link chemical synthesis to photophysical and cellular testing. Initial benchmark compounds validated the feasibility of converting simple fluorophores into effective PSs via minimal structural modifications.
As the project progressed, efforts shifted toward expanding chemical diversity and addressing more demanding objectives, such as achieving NIR absorption in water while maintaining low molecular weight and biological activity against GBM. This phase required extensive synthetic development and resolution of long-standing chemical bottlenecks. In parallel, an integrated biological evaluation pipeline was established, enabling systematic assessment of phototoxicity, selectivity, intracellular behavior, and mechanism of action, and allowing rapid iteration between molecular design and biological outcome.
By the end of the project, InDy had delivered several major scientific breakthroughs. Most notably, the project demonstrated that low-molecular-weight photosensitizers can combine NIR absorption in water with robust and selective activity against GBM. The discovery of such agents was not predictable at the design stage and represents a clear advance beyond the existing state of the art Equally important, the project delivered enabling synthetic methodologies that overcame long-standing barriers in the field and allowed access to previously inaccessible molecular families. These advances were consolidated into a unified InDy design platform. InDy also established entirely new enzyme-responsive PDT paradigms for brain cancers. For the first time, B-galactosidase, monoamine oxidase, and leucine aminopeptidase were shown to function as practical biological triggers for selective light-based brain cancer therapy. These systems combine diagnostic and therapeutic functions and introduce new levels of selectivity and control.
InDy also made a substantial contribution to training and capacity building, involving PhD, MSc, postdoctoral, and undergraduate researchers, and resulting in multiple theses, conference presentations, and high-impact publications. Results were disseminated through peer-reviewed articles in leading journals (i.e. JACS Au), invited seminars, and international conferences (i.e. ACS Meeting), reaching audiences across chemistry, photophysics, and cancer biology. From an exploitation perspective, the project established a protected design platform supported by a European patent, providing a clear pathway for continued preclinical development and translational research.
