Objective
This proposal aims to develop custom designed anticancer therapeutic frameworks that are effective, stable, safe, and tumor targeted, based on the biocompatible TiIV metal. The Tshuva group has established that water stable phenolato TiIV complexes are especially effective as anticancer agents both in vitro and in vivo, with markedly reduced side effects. Optimal derivatives will be developed to combine activity, stability, and biological accessibility, by maintaining small steric bulk while incorporating strong binding donors and hydrophilicity. The mechanism of action will be investigated by chemical and biological methods, including analyzing bio-distribution, cellular pathways and targets, and interaction with bio-molecules. Specifically, the active metal centers will be linked to bioactive moieties through redox-sensitive S–S bonds to enable tumor targeting. Cell penetrating peptides will facilitate cellular penetration for redox-dependent release of the active species selectively in cancer cells; steroid moieties will direct selectivity to hormone-dependent cancer cell types. Since the combination of TiIV- with Pt-based drugs has shown synergistic effects, multi-active entities will include two or more metal centers, possibly also linked to a transport unit. In addition to linear conjugates, polymeric and dendritic assemblies, exploiting the enhanced permeability of cancer cells, will be constructed with theoretically unlimited options for targeted delivery of multiple active sites. Most importantly, flexible well-defined redox-sensitive cages, as well as rigid pH sensitive complex cages, constructed with customized 3D geometries, will enable specific targeting of any active compound or conjugate and selective dissociation only where desired. This study should yield superior anticancer drugs, while unraveling the mystery of their complex biochemistry, and will contribute to the development of novel chemical and medicinal research directions and applications.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
- natural sciences chemical sciences inorganic chemistry transition metals
- natural sciences biological sciences biochemistry biomolecules
- medical and health sciences clinical medicine oncology
- natural sciences mathematics pure mathematics geometry
- medical and health sciences basic medicine immunology immunotherapy
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Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC)
MAIN PROGRAMME
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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.
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.
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.
ERC-COG - Consolidator Grant
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Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) ERC-2015-CoG
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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.
91904 JERUSALEM
Israel
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.