To gain a better understanding of cellular processes, it is crucial to observe which physiological responses are elicited by substances such as signaling agents, pharmaceuticals, or toxins.
This is possible with high spatial and temporal resolution when the active substance is deactivated by a mask that can be removed in a controlled fashion in situ—through irradiation with light. A team led by Peter I. Dalko at the University of Paris (France) has developed a method that also allows for the use of X-rays for unmasking. As the researchers report in the journal Angewandte Chemie, the mask must be equipped with an antenna to receive the X-ray radiation.
Conventional masks come off when irradiated with UV, IR, or visible light. However, this can only penetrate a maximum of about 100 µm deep into tissues. Despite fiber-optic probes and other improved systems for directing the light, it continues to be a challenge to deliver light deeper into tissue. X-rays are able to penetrate several centimeters into soft tissue; however they cannot remove the masks. In order to remove the mask from an active substance, chemical bonds must be broken. This doesn’t work because organic molecules absorb X-rays very poorly.
The French scientists have now used a trick to overcome this hurdle: They use heavy metals as molecular antennas to absorb the X-ray radiation and transfer the energy to the masked molecules.
The researchers deactivate their active molecules by attaching them to an aminoquinoline molecule, a broadly used mask that is normally split off by UV light. For an antenna, they attached a complex of the rare-earth metal gadolinium to this mask. The gadolinium complex was originally developed as a contrast agent for magnetic resonance imaging.
When irradiated with X-rays or gamma rays, the gadolinium absorbs the light energy. This causes one of its electrons to be ejected and transferred to the mask. In consequence, the chemical bond between the mask and the active agent is broken, releasing the agent.
In addition to the study of physiological processes, this method of releasing active substances from their antenna-equipped masks with X-rays could also be a new approach for the phototherapeutic treatment of tumors. A chemotherapeutic agent could be introduced to the body in a masked and thus nontoxic form and targeted to the tumor. As the antenna serves as a probe for magnetic resonance imaging, the tumor can be observed by MRI. By irradiating the tumor with X-rays, the masked agent can be photolyzed locally to release the active agent very specifically in the diseased tissue. This would protect healthy tissue and reduce side effects.Author: Peter I. Dalko, Université Paris Descartes (France), http://www.biomedicale.parisdescartes.fr/umr8601/DALKO-Peter.html
Angewandte Chemie International Edition, Permalink to the article: http://dx.doi.org/10.1002/anie.201102948
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