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DuoLipo-TNP: Dual-Responsive Liposome Platform for Selective Delivery of Triphosphate Nucleotide Prodrugs in Triple-Negative Breast Cancer

Project description

Smart nanoparticles for precision drug delivery

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer that lacks expression of oestrogen and progesterone receptors, and the HER2 protein. As a result, standard hormone therapies and targeted treatments are ineffective. The TNBC microenvironment is characterised by poor vascularisation and low oxygen levels, making effective drug delivery particularly challenging. With the support of the Marie Skłodowska-Curie Actions programme, the DuoLipo-TNP project aims to develop liposomal nanocarriers that respond to the acidity and low oxygen of the tumour microenvironment, thereby facilitating site-specific drug release. This approach utilises targeting peptides that guide the nanocarriers to tumour blood vessels, enhancing selectivity and minimising systemic toxicity.

Objective

Breast cancer is the most frequently diagnosed cancer in women worldwide and a leading cause of cancer mortality in Europe, with triple-negative breast cancer (TNBC) representing the most aggressive and therapy-resistant subtype. Driven by tumor heterogeneity, poor vascularization, and a hostile microenvironment, TNBC urgently requires new therapeutic strategies, an unmet clinical need directly aligned with the EU Mission on Cancer. DuoLipo-TNP seeks to address these challenges by developing dual-responsive liposomal nanocarriers for the selective delivery of γ-masked triphosphate nucleotide prodrugs (TNPs). The platform combines tumor-penetrating iRGD peptides for αvβ3/αvβ5 integrin-mediated vascular targeting with lipid components responsive to hypoxia and acidic pH, two hallmark features of TNBC. This dual-triggered strategy enables site-specific release of active antimetabolites, bypasses kinase-dependent activation, and minimizes systemic toxicity. The project applies a multidisciplinary approach spanning prodrug synthesis, advanced liposomal formulation and characterization, and comprehensive pharmacological validation in 2D and 3D TNBC models, including patient-derived spheroids. Ultimately, DuoLipo-TNP aims to establish a platform for intratumoral delivery of nucleotide analogues, advancing precision nanomedicine and contributing to the EU Mission on Cancer by improving outcomes in drug-resistant solid tumors.

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HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships

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(opens in new window) HORIZON-MSCA-2025-PF

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Coordinator

CARDIFF UNIVERSITY
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.

€ 260 347,92
Address
RESEARCH SERVICES C/O MAIN BUILDING
CF10 3AT CARDIFF
United Kingdom

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Region
Wales East Wales Cardiff and Vale of Glamorgan
Activity type
Higher or Secondary Education Establishments
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Total cost

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