PhoRAu · Photochemistry and radiolabelling of gold(III) anticancer prodrugs
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2018-03-01 → 2020-02-29
- EU contribution
- €158,122
- Participants
- 1
- Scheme
- MSCA-IF
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Results in brief
Photochemistry and radiolabelling of gold(III) anticancer prodrugs
The social impact of cancer demands that medicinal inorganic chemists introduce innovative approaches and chemical tools for the treatment of cancer. Cisplatin and its approved derivatives continue demonstrating how transition metal complexes play a major role in the clinical treatment of cancer. In the last 15 years, the need to find an alternative to cisplatin and its analogues, enormously boosted the research on gold compounds as new valuable agents to treat cancer. Most of the studies on the anticancer activity of Au-NHCs concern Au(I) complexes. Reports on Au(III)-NHCs are more recent, and the stability of these compounds in biological environment is an issue not always exhaustively investigated. Knowledge on the fate of Au(III)-NHCs after their administration in vivo is still largely insufficient. The study of the biodistribution of Au(III) compounds in vivo and the evaluation of their metabolization to Au(I) species is a very challenging task that has not been thoroughly addressed so far, albeit this is a key step in drug development PhoRAu aspires to: • Develop new gold (pro)drug candidates based on the Au(III)-NHC scaffold; • Label such Au(III)-NHC complexes with long-lived Iodine-124 (124I) for use as nuclear imaging agents. • Study the biodistribution of one radio-labelled Au(III)-NHC complex via Postron Emission Tomography (PET).
Data: CORDIS, © European Union
Project objective
The use of light to activate anticancer prodrugs is nowadays a reality in clinics around the world. Photodynamic therapy is an effective treatment for the localised destruction of cancer cells in a range of tissues and organs. Triggering the antiproliferative activity of chemotherapy agents with spatial and temporal control offers the advantage of reducing side effects and resistance. On the bases of the great success of metal-based drugs (e.g. cisplatin and its derivatives), photoactivatable metal complexes have been investigated for their potential in light-activated therapy. This promising class of molecules is characterised by outstanding photophysical and photochemical features, which can result in novel cytotoxicity mechanisms. Among transition metals, gold has shown promising anticancer features, however no attempt to exploit Au photochemistry for medicinal use has been reported yet.This project aims at exploring such potential by investigating the development of innovative photoactivatable gold complexes that can be used as effective prodrugs for photochemotherapy and simultaneously act as imaging agents.In particular, the research plan involves the synthesis of novel gold(III) carbene complexes which display dark stability in physiological conditions and high reactivity under light irradiation. These systems can undergo controlled Au(III)/Au(I) reduction in cell compartments giving new cell killing modes and therapeutic advantages. Strikingly, their remarkable synthetic and chemical versatility are ideal for combining therapy and imaging capabilities through labelling with 124-I radionuclide for Positron Emission Tomography (PET). Integration of such features has the potential to deliver innovative image-guided agents for cancer phototherapy.
Original text from CORDIS.
Participants
- FUNDACION DONOSTIA INTERNATIONAL PHYSICS CENTER · Donostia San SebastianCoordinatorSpain
Links
Data: CORDIS, © European Union