ModEMUS · Modelling nanoparticle transport in the extracellular matrix: improving drug delivery with ultrasounds
Horizon Europe — Marie Skłodowska-Curie Actions
- Duration
- 2023-08-01 → 2025-08-31
- EU contribution
- €210,911
- Participants
- 2
- Scheme
- HORIZON-TMA-MSCA-PF-EF
Lines connect the coordinator with its partners.
Results in brief
Modelling nanoparticle transport in the extracellular matrix: improving drug delivery with ultrasounds
Cancer remains the second leading cause of death in Europe, with 2.27 million new cases and 1.3 million deaths recorded in 2020. Despite advances in therapy, fewer than 1 % of systemically administered drugs reach solid tumours, limiting treatment effectiveness and increasing side effects. Nanoparticle (NP) drug delivery offers a promising strategy by exploiting tumour vasculature permeability, but achieving uniform NP distribution within tumour tissue remains a major challenge. A key barrier is the extracellular matrix (ECM) — a dense network of collagen fibres and proteoglycans that hinders drug diffusion. Focused ultrasound (FUS), especially when combined with microbubbles, has shown potential to enhance NP penetration by generating mechanical effects such as acoustic radiation force and cavitation. However, the mechanisms driving these improvements are not fully understood, and the outcome depends on multiple interacting factors, including tumour pathology, ECM composition, NP properties, and FUS parameters. This project addresses these challenges by developing a molecular modelling framework to predict NP transport through the ECM under FUS exposure. By correlating molecular-scale interactions with experimental data, the model will identify optimal NP designs and FUS protocols for enhanced delivery. The results are expected to accelerate the development of personalised, NP-based cancer therapies, supporting EU health priorities to reduce cancer mortality and improve patients’ quality of life.
Data: CORDIS, © European Union
Project objective
Cancer is the second most important cause of death in Europe, with an estimated 2.27 million new cases and 1.3 million deaths in 2020. The prerequisite for a successful medicinal therapy is that the drug reaches its target and that toxicity towards healthy tissue is limited, however the systemic injection of drugs leads to less than 1 % of the drugs accumulating in solid tumours. Relying on the permeability of the blood vessel in cancer tumours, the encapsulation of drugs in nanoparticles (NPs) constitutes a promising approach for cancer treatment. However, the homogeneous distribution of NPs in the tumour tissue remains a challenge. To reach all cells in the tumour the NPs must cross the extracellular matrix (ECM), a major component of solid tumours consisting mainly of a network of collagen fibres embedded in a hydrophilic gel of proteoglycans. Together, they limit the diffusion of drugs across the tumour. Focused UltraSound (FUS) exposure has been reported to improve the delivery of NPs to tumour cells. FUS induces acoustic radiation force and cavitation that can lead to microstreaming or shock waves but the underlying mechanism(s) for the improved transport are not well understood. Successful delivery depends on many factors including the pathology, structure and composition of the diseased tissue, the characteristics of the NPs, and the exposure parameters of the FUS, making it a complex problem difficult to solve using an experimental approach. In this project, we will use molecular modelling to identify correlations between the molecular details of NPs and ECM, and FUS exposure parameters with NP transport across the ECM, creating a predictive model for FUS delivery of NPs and drugs to diseased tissue. The model, validated by experimental data, will contribute to the design of personalized medicine for improved NP-based drug delivery.
Original text from CORDIS.
Participants
Links
- View on CORDIS
- DOI: 10.3030/101062456
- https://ec.europa.eu/research/participants/documents/downloadPublic?documentIds=080166e507873719&appId=PPGMS
- https://ec.europa.eu/research/participants/documents/downloadPublic?documentIds=080166e51f5141a0&appId=PPGMS
Data: CORDIS, © European Union