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Bioorthogonal Photocatalytic Activation of Metal-Based Prodrugs

Objective

New cancer care methodologies with fewer side effects and no need for major surgery are required to enhance patient wellbeing. Photodynamic Therapy (PDT) partially accomplishes such mission employing light and a photosensitizer. Nevertheless, the PDT mechanism of action intimately depends on oxygen, which limits its efficacy, particularly in hypoxic solid tumours. Promising strategies to improve the impact of PDT in the clinics currently involve the design of photoactivatable transition metal complexes, a class of compounds which combines the rich photochemistry of metal complexes with the vast background of metal-based drugs in cancer therapy.

In this framework, ORTHOCAT proposes an original and multidisciplinary strategy to exploit the efficiency and selectivity of riboflavin as unconventional photocatalyst for the activation of Pt(IV) anticancer prodrugs (Chem. Sci. 2017, 8, 4619).

The project aims at designing novel riboflavin-based catalytic systems capable of activating Pt(IV) anticancer prodrugs inside the mitochondria of tumour cells. In particular, I will use triphenylphosphonium targeting vectors to develop new photocatalytic prodrug systems and delivery nanoplatforms which selectively accumulate in the mitochondria. Once in the organelle, riboflavin will act as singlet oxygen photosensitizer for PDT and simultaneously as photocatalyst to generate Pt(II) species for targeting mitochondrial DNA (photochemotherapy). Imbalance of mitochondrial delicate redox homeostasis by ORTHOCAT dual agents can trigger cell death through convenient cellular pathways. Therefore, ORTHOCAT prodrug systems will synergistically kill cancer cells with increased effectiveness, while potentially reducing side effects of metal-based drugs. Successful outcome of the project has the potential to deliver innovative therapeutic agents for cancer photochemotherapy.

Fields of science (EuroSciVoc)

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Programme(s)

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Topic(s)

Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.

Funding Scheme

Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.

MSCA-IF-EF-ST - Standard EF

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Call for proposal

Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.

(opens in new window) H2020-MSCA-IF-2017

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Coordinator

FUNDACION DONOSTIA INTERNATIONAL PHYSICS CENTER
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 158 121,60
Address
PASEO MANUEL LARDIZABAL 4
20018 Donostia San Sebastian
Spain

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Region
Noreste País Vasco Gipuzkoa
Activity type
Research Organisations
Links
Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 158 121,60
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