University of Zurich/ Department of Chemistry/ Phototherapeutics

Description

The Lab of Prof. Bernhard Spingler is a research group at the University of Zurich, working at the intersection of medicinal chemistry, phototherapy, and molecular medical materials science. The group’s major research topic is organised around the development of advanced photosensitizers for therapeutic applications in oncology, such as melanoma, cutaneous squamous-cell carcinoma, cutaneous t-cell lymphoma, etc. including the corresponding murine models.

In the field of medicinal chemistry, the lab aims to improve the efficacy and selectivity of photodynamic therapy (PDT) and photothermal therapy (PTT). A key focus is the rational design of photosensitizers following the laws and principles of physical organic chemistry. Photosensitizers from the Spingler Lab combine strong light-induced cytotoxicity with minimal dark toxicity. Previous studies led to the synthesis of novel nanometre-sized porphyrin–platinum conjugates, which showed pronounced phototoxic effects against various human cancer cell lines while remaining essentially non-toxic in the absence of light. A new class of lead photosensitizers, so called BODIPYs, achieve outstanding light-to-dark toxicity ratios exceeding 830’000 under normoxic conditions and more than 360’000 under severe hypoxia (0.2% O₂), following irradiation at 630 nm. These properties make them particularly attractive for applications in solid tumours and hypoxic disease environments. The lab’s work has resulted in high-impact publications, including a landmark contribution in the Journal of the American Chemical Society[1], underscoring its role in advancing phototherapeutic science.

Within an existing collaboration with cancer scientists and immunologists at the University Hospital Zurich (UZH), the lab explores the use of photosensitizers in photochemical internalisation approaches for the delivery of anti cancer vaccines. Within Horizon Europe Cluster Health Calls, the Spingler lab is reaching out to the preclinical science community for collaborations aiming to develop treatments for antimicrobial-resistant pathogens (AMR)[2–4] and viral infections[5–7], where photosensitizers are either administered as small molecules or as conjugates with peptides, RNA, antibodies/ DARPins, etc. Within this scope, one of our basic science goals is to generate much-needed ADMET data of the BODIPY parents to support the translational science development of this new class of theranostics up to First-in-Human Clinical Trials.

The Spingler lab’s work has resulted in high-impact publications, including a landmark contribution in the Journal of the American Chemical Society[1], underscoring its role in advancing phototherapeutic science.

Bibliography

[1]        L. Schneider, M. Kalt, S. Koch, S. Sithamparanathan, V. Villiger, J. Mattiat, F. Kradolfer, E. Slyshkina, S. Luber, M. Bonmarin, C. Maake, B. Spingler, Z. O. Repository, ‘BODIPY-Based Photothermal Agents with Excellent Phototoxic Indices for Cancer Treatment’, J Am Chem Soc 2023, 145, 4534–4544.

[2]        Q. Shi, C. Mou, Z. Xie, M. Zheng, ‘Exploring BODIPY derivatives as photosensitizers for antibacterial photodynamic therapy’, Photodiagnosis Photodyn Ther 2022, 39, 102901.

[3]        Y. Guan, B. Yu, J. Ding, T. Sun, Z. Xie, ‘BODIPY photosensitizers for antibacterial photodynamic therapy’, Chinese Chemical Letters 2025, 36, DOI 10.1016/j.cclet.2024.110645.

[4]        Yao Liu, Rong Qin, Sebastian A. J. Zaat, Eefjan Breukink, Michal Heger, ‘Antibacterial photodynamic therapy: overview of a promising approach to fight antibiotic-resistant bacterial infections’, J Clin Transl Res 2015, DOI 10.18053/jctres.201503.002.

[5]        H. Kunstek, F. Vreken, A. Keita, M. R. Hamblin, F. Dumarçay, M. Varbanov, ‘Aspects of Antiviral Strategies Based on Different Phototherapy Approaches: Hit by the Light’, Pharmaceuticals 2022, 15, 858.

[6]        J. Bartosińska, D. Kowalczuk, P. Szczepanik-Kułak, M. Kwaśny, D. Krasowska, ‘A review of photodynamic therapy for the treatment of viral skin diseases’, Antivir Ther 2025, 30, DOI 10.1177/13596535251331728.

[7]        M. Krasilnikov, P. Strakova, J. Holoubek, ‘Photosensitizing fluorescent dyes based on BODIPY scaffold as broad-spectrum antiviral drugs (Poster P-46-005)’, FEBS Open Bio 2025, 15, 508–509.

About the Organization's Cover Picture: The cover was taken from the front page of JACS 2023, 145, where [1] was published and illustrates light-activated photothermal cancer therapy using BODIPY-based agents. Upon irradiation, the molecules convert light into localized heat that penetrates a three-dimensional multicellular tumor spheroid, symbolizing effective tumor damage. The imagery highlights oxygen-independent activity together with strong phototherapeutic effects and low dark toxicity.