Doctoral themes 2023

 Ruthenium prodrugs as smart theranostic agents for cancer therapy 

Supervisors

Tânia S. Morais, tsmorais@ciencias.ulisboa.pt

Jaime A. S. Coelho, jacoelho@ciencias.ulisboa.pt

Registration Institution

Faculdade de Ciências, Universidade de Lisboa

Project description

 Cancer is one of the main causes of death in the world. Its growing incidence and mortality is one of the most important public health challenges of this century. Despite decades of global efforts, there is still no cure for cancer and the 5-year survival rate remains low due to late diagnosis and lack of efficient/specific therapies.

This project aims to explore these limitations through the development of theranostic agents with the dual action of early diagnosis and targeted therapy. The structure of these smart theranostic agents exploits the differences between cancerous and healthy cells, thus containing a targeting unit and functional groups sensitive to tumor stimuli to increase the diagnostic and therapeutic efficiency through the controlled release of the drug/probe selectively in the target.

In this project, new targeted ruthenium-probe conjugates will be developed, whose structure is based on ruthenium complexes that have already shown to be effective in vitro/in vivo against various tumors[1,2], conjugated to probes with high affinity for overexpressed receptors in cancer cells. This system is designed to be inactive during delivery, but upon reaching the targeted site, the linker is cleaved and both the Ru drug and the previously masked probe in their active forms are selectively released into the tumor.

The Ph.D. student will acquire a strong knowledge of inorganic/organometallic and organic synthesis and several characterization techniques. The biological evaluation will be carried out at FCT.NOVA under ongoing collaborations. A short-term visit to TUM is planned to evaluate the diagnosis properties of these systems.

References: [1] Nuno Mendes et al., AntiCancer Agents in Med. Chem., 2017, 17(1), 126. [2] Tânia S. Morais, et al., Fut. Med. Chem., 2016, 8(5), 527.

Keywords

Targeted theranostic agents

Drug delivery

Cancer therapy

Early diagnosis

Synthesis