Gold-Triggered Uncaging Chemistry in Living Systems Opens New Frontiers for Cancer Therapy

The University of Edinburgh| Fri Aug 04 01:22:30 EDT 2017
Gold-Triggered Uncaging Chemistry in Living Systems Opens New Frontiers for Cancer Therapy

Bioorthogonal chemistry – chemical reactions that can occur inside of living systems without interfering with native biochemical processes – may hold the key for better targeted therapeutic approaches with less negative side-effects in the future: July 2017

Bioorthogonal chemistry – chemical reactions that can occur inside of living systems without interfering with native biochemical processes – may hold the key for better targeted therapeutic approaches with less negative side-effects in the future. This is because they enable production of biologically active drugs from harmless chemical compounds (prodrugs) in strictly defined locations in a living organism, a feature that could be of particular benefit in cancer therapy where cytotoxic drugs distributed in the whole body often target not only tumour site but also healthy tissues and organs causing fatigue, nausea and other adverse effects.

Using metal implants as catalysts that trigger bioorthogonal chemistry reactions in precisely defined places in the body is a very promising experimental strategy, however it is challenging as they display limited biocompatibility in living systems both in terms of catalytic versatility and inherent toxicity.

In the work entitled “Gold-Triggered Uncaging Chemistry in Living Systems” that has recently been published in the journal Angewandte Chemie International Edition, scientists from the University of Edinburgh and the University of Zaragoza, led by Dr Asier Unciti-Broceta from the Cancer Research UK Edinburgh Centre and Prof Jesús Santamaría from the Institute of Nanoscience of Aragon, developed a heterogeneous catalytic system that enables access to chemical properties of gold nanoparticles that were previously out of our reach in biological environments.  This innovative study, which includes the first bioorthogonal organometallic reaction to be locally performed in the brain of a living animal, proves the capacity of heterogeneous gold catalysts to mediate the spatially controlled release of therapeutics. It supports a potential application scenario where gold-functionalized implants could be used in situ to modulate the spatiotemporal generation of chemotherapeutics from inactive precursors in the treatment of localized malignancies such as brain or prostate cancer.

 

There is still a lot to be done before this strategy can be used in the clinic, but the work opens new exciting frontiers in bioorthogonal chemistry as gold is the safest metal for humans. We hope that the developed approach could be used one day to selectively activate cytotoxic drugs in direct proximity of a tumour site, thus reducing the harmful effects to other parts of the body


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