Objective
Glioblastoma multiforme (GBM) is a grade IV glioma, considered as the most aggressive brain tumor with an average five-year survival rate of 7.2% and projected mortality rate of 46.6% by 2040. The prognosis remains poor, not only due to the severity of the disease but also due to challenges in treatment modality and recurrence. Temozolomide (TMZ) is the preferred anticancer drug for GBM owing to its effectiveness in reducing relapse but the efficacy is compromised by substantial hurdle of drug resistance. My strategy is to overcome this challenge and revolutionize GBM treatment by addressing the obstacles associated with TMZ resistance and prioritizing patient compliance. I hypothesize that combining a small dose of NO-releasing NONOates will activate p53 and inhibit HIF-1, effectively blocking TMZ resistance pathway and significantly boosting therapeutic efficacy. Moreover, NO dilates tumor blood vessels, enhancing the permeation and retention effect (EPR) which increases biodistribution of TMZ within the tumor, promoting apoptosis and oncogenic stress signals thereby reducing the likelihood of tumor recurrence. While the combination of TMZ and NONOates offers numerous advantages for efficient delivery, a major challenge remains: ensuring the transport across the blood brain barrier (BBB) to the tumor site. Here, I also propose the development of an enzyme-triggered injectable hydrogel encapsulating NONOates and TMZ nanocrystals (NCs) designed for post-resection GBM. The enzymatic crosslinking process involves oxidative coupling of catechol groups of tyramine-modified biomolecules, while TMZ NCs will be fabricated via antisolvent co-sonoprecipitation method. The in-situ hydrogel forms rapidly, adhering stably to the resection site, ensuring a targeted and sustained release of TMZ and enhancing efficacy through the synergistic action of NONOates. The combination of NCs, NONOates and enzyme-triggered gelation provides a robust platform for targeted GBM therapy.
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: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- social sciences sociology demography mortality
- natural sciences biological sciences biochemistry biomolecules
- engineering and technology nanotechnology nano-materials nanocrystals
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Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
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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HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA)
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.
HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships
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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) HORIZON-MSCA-2024-PF-01
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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.
D02 CX56 Dublin
Ireland
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.