Available online 15 September 2025, 104477

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Zebrafish embryos enable microscope imaging of light-controlled drug actions.

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Zebrafish allow light-based modulation of drug effects.

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Zebrafish embryos provide a platform for testing light-activated drugs.

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Zebrafish offer well-characterized mechanisms for studying photoswitch activation.

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Light-activated drugs induce light-dose-dependent malformations in zebrafish.

Abstract

Photopharmacology is an emerging field of pharmacological sciences that enables precise spatiotemporal control over drug activation with light. In its reversible mode, it relies on photoswitchable bioactive compounds. The capacity to reversibly activate and deactivate drugs derivatized with photoswitches enables us to avoid side effects and environmental toxicity. Zebrafish represent an emerging and privileged model for translational photopharmacology because of their optical transparency at early developmental stages, genetic tractability, and well-characterized biological mechanisms. In this review, we discuss the use of zebrafish in advancing photopharmacology and understanding the effects of light-controlled interventions using photoswitchable bioactive compounds.

Section snippetsPrinciples and goals of photopharmacology

Photopharmacology is an emerging area within biomedical research, which aims to overcome challenges encountered in pharmacological treatments like the emergence of side effects and the development of drug resistance.1 Photopharmacology uses light as an external stimulus to control bioactive molecules, allowing for external modulation of drug activity with minimal photon toxicity.1 The use of light in this context offers advantages such as avoiding contamination of the study object, ease of

Zebrafish toolbox for photoswitchable compounds studies

Zebrafish (Danio rerio) is a small tropical freshwater teleost fish that belongs to the Cyprinidae family and lives in natural waters and rice fields in South Asia, North India, and Pakistan.8 Zebrafish is an established vertebrate model in pharmacology because of its rapid maturation and easy manipulation. It is highly fertile, allowing it to produce at least 200 eggs per clutch every 2–3 days, which can be used for experiments even in the early stages of development.9 Furthermore, following

Limitations in the use of zebrafish in photoswitchable drugs studies

A significant number of studies have been performed in the fields of developmental biology, neuroscience, pharmacology, and imaging using photoswitchable drugs in zebrafish. However, the use of zebrafish still presents certain biological and technological challenges.

Concluding remarks

The zebrafish is an animal model of choice for early in vivo photopharmacology studies because of characteristics that allow the application of photoswitchable drugs in a biological context. Its transparency and rapid development enable optical control and monitoring of morphological effects of biological processes. This also permits the direct observation of physiological processes like blood circulation and heartbeat,[12], [17], [27] showing additional possibilities for experiments with

CRediT authorship contribution statement

Guilherme Pietro da Silva: Writing – review & editing, Writing – original draft, Investigation, Conceptualization. Janine Doorduin: Writing – review & editing, Writing – original draft, Investigation. Wiktor Szymanski: Writing – review & editing, Writing – original draft, Investigation, Conceptualization. Rosane Souza da Silva: Writing – review & editing, Writing – original draft, Supervision, Investigation, Conceptualization. Philip Elsinga: Writing – review & editing, Supervision,

Funding

This study was funded in part by Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - Brasil (CAPES) - finance code 001 and Instituto Nacional de Ciências e Tecnologia para Doenças Cerebrais, Excitotoxicidade e Neuroproteção. G.P.S is recipient of a fellowship from CAPES. C.D.B. (Proc.306115/2023-9) and R.S.S (Proc. 307825/2022-1) are recipients of Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) research productivity grants. The study was also funded by the

Declaration of interests

No interests are declared.

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