Molecular tattoo: subcellular confinement of drug effects

Technological resources for sustained local control of molecular effects within organs, cells, or subcellular regions are currently unavailable, even though such technologies would be pivotal for unveiling the molecular actions underlying collective mechanisms of neuronal networks, signaling systems, complex machineries, and organism development. We present a novel optopharmacological technology named molecular tattooing, which combines photoaffinity labeling with two-photon microscopy. Molecular tattooing covalently attaches a photoreactive bioactive compound to its target by two-photon irradiation without any systemic effects outside the targeted area, thereby achieving subfemtoliter, long-term confinement of target-specific effects in vivo. As we demonstrated in melanoma cells and zebrafish embryos, molecular tattooing is suitable for dissecting collective activities by the separation of autonomous and non-autonomous molecular processes in vivo ranging from subcellular to organism level. Since a series of drugs are available for molecular tattoo, the technology can be implemented by a wide range of fields in the life sciences.