Ultrasound-mediated drug delivery to tumors and across the blood-brain barrier
Successful cancer therapy depends on the ability of drugs to reach all cancer cells. This requires prolonged circulation in the bloodstream, efficient extravasation across capillary walls, penetration through the extracellular matrix, cellular uptake, and intracellular transport to the therapeutic target. A major challenge in chemotherapy is the low accumulation of drugs in tumors.
Encapsulating drugs in nanoparticles can modestly improve tumor uptake due to the leaky tumor vasculature and impaired lymphatic drainage. A major advantage using nanoparticles is the reduced toxicity to healthy tissues. However, nanoparticle distribution within tumors remains heterogeneous, with most nanoparticles accumulating near blood vessels, limiting their therapeutic potential. Drug delivery to the brain is even more challenging due to the physical barrier formed by the blood-brain barrier.
Ultrasound focused on the tumor combined with microbubbles circulating in the blood has demonstrated promising potential in both clinical and preclinical (e.g., murine) studies for enhancing drug and nanoparticle delivery to tumors. The primary mechanism involves microbubble oscillations in the ultrasound field, generating microstreaming and shear stress on capillary walls. This process increases vascular permeability and promotes extravasation. Following extravasation, nanoparticles must traverse the dense extracellular matrix to reach cancer cells. The impact of ultrasound on this transport step is less well understood but may involve mechanisms such as acoustic streaming and oscillatory diffusion.
The talk will address the key barriers to effective nanoparticle delivery and discuss the mechanisms by which ultrasound can enhance their transport.
Short bio: Catharina completed her MSc and PhD in Physics at The Norwegian University of Science and Technology (NTH) and the University of Oslo (UiO). She spent ten years at the Norwegian Radium Hospital, working in the Department of Environmental and Occupational Cancer, the Institute of Cancer Research, and the Department of Biophysics. In 1991, she joined the Norwegian University of Science and Technology (NTNU), where she is currently a Professor in the Department of Physics.
Projects: NFR- FRIMEDBIO; NFR-FRIPRO; NFR -Nano; Helse Midt-Norge
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