The research was carried out by the groups of Dr Tomáš Šolomek at the University of Amsterdam’s Van ‘t Hoff Institute for Molecular Sciences and Dr Peter Štacko at the University of Zurich (Department of Chemistry).

Photocages are photochemical tools that offer a control over substrate activity precisely in time and space using light as a bio-orthogonal stimulus. They do so by releasing molecules upon light absorption by an attached chromophore. Photocages thus permit activation of proteins, nucleotides, drugs, and other biologically significant molecules. This positions them as prime contenders for photoactivated chemotherapy, a strategy that complements the photodynamic therapy that is already applied in healthcare.

Practical relevance

For photocages to be adopted in therapy, they have to respond to tissue-penetrating, benign light with sufficient photochemical efficiency. In their Chemical Science paper, the researchers show how they tackled this major challenge by designing photocages based on a family of dyes (cyanines 7) that already have widespread use in bioimaging applications.

The newly-developed photocages can be activated at 850 nm in the near infrared (NIR) region. By increasing the initial photochemical efficiency by two orders of magnitude, the research team was able to arrive at activation efficiencies of practical relevance. Light exposure of several hours can now release the full dose of the photocages’ cargo. At the same time, the team determined experimentally that there is a thermodynamic limit beyond which the current photocages cannot be excited (<1000 nm) and practically used.

Abstract, as published with the paper

Near-infrared light-activated photocages enable controlling molecules with tissue penetrating light. Understanding the structural aspects that govern the photouncaging process is essential to enhancing their efficacy, crucial for practical applications. Here we explore the impact of thermodynamic stabilization on contact ion pairs in cyanine photocages by quaternarization of the carbon reaction centers. This strategy enables the first direct uncaging of carboxylate payloads independent of oxygen, resulting in a remarkable two-orders-of-magnitude enhancement in uncaging efficiency.

Our computational analyses reveal that these modifications confer a kinetic instead of thermodynamic effect, reducing ion–ion interactions and allowing complete separation of free ions while inhibiting recombination. We demonstrate that, while thermodynamic stabilization is effective in traditional chromophores operating at shorter wavelengths, it rapidly reaches its thermodynamic limitations in NIR photocages by compromising the photocage stability in the dark.

Thanks to these findings, we establish that activation of cyanine photocages is limited to wavelengths of light below 1000 nm. Our work illuminates the path to improving uncaging cross-sections in NIR photocages by prioritizing kinetic trapping and separation of ions.

Paper details

Hana Janeková, Sergey Fisher, Tomáš Šolomek, and Peter Štacko: Surfing the limits of cyanine photocages one step at a time. Chemical Science 2025, Advance Article. Chem. Sci., 2025, 16, 1677-1683 DOI: 10.1039/D4SC07165D. Cover DOI: 10.1039/D5SC90022K

See also

• Website Šolomek Lab
• Website Štacko group