Multimodal theranostics in oncology

Overall scientific concepts and goals

The “Imaging and Biomarkers in Oncology” lab is focused on the discovery, development, and clinical translation of theranostic strategies for cancer, bridging basic research and translational efforts in nuclear medicine, molecular imaging, and targeted therapies. Its overarching aim is to enhance cancer patient outcomes through innovative approaches covering early tumor detection, therapy monitoring, radioligand therapy, targeted drug delivery, and intraoperative precision guidance. By leveraging tumor-specific biomarkers, we develop highly selective agents for PET/SPECT imaging and targeted radioligand therapy, as well as novel conjugates for cytotoxic or targeted drug delivery — addressing critical unmet clinical needs across a broad spectrum of cancer types (Fig. 1). We combine this breadth of topics with a systems-level analysis of molecular mechanisms of resistance and toxicity, applying interdisciplinary techniques from chemistry, cell biology, molecular imaging, and immunology within a research environment that fosters collaboration across local, national, and international partners.

Monitoring the photochemical reactivity of 2-D materials

Two-dimensional transition metal dichalcogenides (2-D TMDs) are promising material platforms for optoelectronics, sensing, and quantum information technologies, showing significant potential for groundbreaking applications. They also hold immense potential for photocatalysis, due to their earth-abundance, strong light-matter interaction, and high surface-to-volume ratio, which means they can host many active sites for chemical reactions. However, progress has been limited due to an incomplete understanding of their photocatalytic reactive sites and their reactivity.

Therefore, it is essential to identify active chemical sites and monitor their reactivity under appropriate operando conditions, using advanced approaches that can probe these aspects. Employing this unique, performance-oriented feedback, the material synthesis can be optimized regarding morphology, dopants, and other defects. This will provide a deeper understanding that will lead to novel photocatalyst design, fully leveraging the tunability of 2-D TMDs to develop next-generation materials and set new benchmarks in efficiency and sustainability.

To accomplish this goal, we developed a novel operando imaging method capable of identifying the spatial distribution of reactive sites for oxidation and reduction on a 2-D TMD: an MoS₂ monolayer (ML), using light as the sole external driving force (see Fig. 3). We observed the effects of the electronic properties of the material, electron/hole transport, and lateral confinement of photocarriers on chemical reactivity. Unlike other imaging techniques that have been recently utilized to study photocatalytic systems, this new imaging method enables the direct mapping of efficiency with high spatial resolution (~200 nm) and allows the local measurements of hydrogen generation under light excitation for the first time.

The separation and transport of charge carriers during photocatalysis are also critical factors in solar-driven devices. Building on insights from our study, we explored strategies to enhance charge carrier mobility on 2-D platforms. We observed a significant improvement in the efficiency of MoS₂ under visible light, with charge extraction increasing by 5 to 30 when connected to a conductive material. Notably, this enhanced performance extended over distances of several hundred micrometers from the connection point.

These findings offer a clear path toward designing highly efficient sunlight-powered devices by improving charge transport over long distances and optimizing photocatalytic performance. Such advancements could significantly impact solar energy conversion technologies, hydrogen production, and sustainable energy systems.