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Breaching the protective cancer stroma with radiotherapy-responsive liposomes

Objective

Liposomes have been the most successful type of nanomedicine for cancer patients, playing a leading role in improving the tolerability of chemotherapeutics. However, to advance the success of liposomal drug delivery and cancer treatment, new approaches to physically trigger drug release in cancer tissues and increase the permeability of the protective cancer stroma are needed. This project will investigate whether radiocatalytic nanomaterials can be integrated in liposomes for spatiotemporal-controlled drug release, the alleviation of cancer desmoplasia, and improved efficacy of co-encapsulated drugs.

Liposomes will be composed of oxidation-susceptible phospholipids that encapsulate hydrophilic drugs in their aqueous core. Radiation-absorbing nanomaterials will be included in the liposomes to produce high levels of reactive oxygen species when activated by X-rays. This will oxidize the liposomes and facilitate the release of the encapsulated drugs. Simultaneously, the cytotoxicity of the oxidants is expected to reduce the high cell densities in the tumor periphery, enabling the therapeutics to deeply permeate the cancer tissues following their release. This customizable strategy will be developed in the context of pancreatic cancer, a chemoresistant form of cancer with poor survival rates. This project develops a multidisciplinary approach to investigate the physicochemical mechanisms of radiotherapy-induced drug release, adaptive optics microscopy to study tissue permeability in 3D cultures of desmoplastic pancreatic cancer, and multimodal in vivo imaging to uncover the therapeutic potential and mechanisms.

Radiotherapy-controlled drug release from liposomes is a ground-breaking novel concept, and its capacity to increase cancer tissue permeability has never before been demonstrated. When successful, new avenues for controlled liposomal drug delivery will emerge that can significantly advance the standard-of-care for many cancer patients.

Fields of science (EuroSciVoc)

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Keywords

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Programme(s)

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Topic(s)

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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.

HORIZON-ERC - HORIZON ERC Grants

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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) ERC-2022-STG

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Host institution

INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE
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.

€ 1 942 158,00
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.

€ 1 942 158,00

Beneficiaries (1)

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