Project description
Modelling nanoparticle transport induced by ultrasound to improve drug delivery
The delivery of drugs encapsulated in nanoparticles (NPs) represents a promising approach in cancer treatment. However, NP delivery to cells in tumours is hindered by the extracellular matrix (ECM), a network of collagen fibres in a gel of proteoglycans. Focused ultrasound (FUS) irradiation and its combination with microbubbles have been shown to improve the delivery of NPs to tumours. Successful delivery depends on factors such as pathology, ECM structure, NP characteristics, and FUS exposure parameters, making it a complex problem that is difficult to tackle using experimental approaches. Funded by the Marie Skłodowska-Curie Actions programme, the ModEMUS project will use molecular modelling to find correlations between those parameters and NP transport across the ECM, improving NP delivery to diseased tissue.
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.
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.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques.
- natural sciencesphysical sciencescondensed matter physicssoft matter physics
- medical and health sciencesclinical medicineoncology
- natural sciencesbiological sciencesbiophysics
- engineering and technologynanotechnologynano-materials
- natural sciencesphysical sciencesacousticsultrasound
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Keywords
Programme(s)
- HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA) Main Programme
Funding Scheme
HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European FellowshipsCoordinator
7491 Trondheim
Norway