Ultrasound-mediated delivery of nanoparticles

Delivery of therapeutic agents administered intravenously to solid tumor tissue, in optimal quantities with a limited exposure to normal tissue, is challenging. This challenge can be partially overcome using nanoparticles and microbubbles combined with ultrasound. Hence, the purpose of the experiments is to the study the extravasation, behavior and distribution of nanoparticles when exposed to ultrasound in solid tumor growing in window chambers in mice. The nanoparticles will be imaged in real time using multiphoton microscopy. This imaging method is the only one that provides high enough spatial resolution that can distinguish between nanoparticles inside and outside the blood vessels (extravasation), and their behavior and distribution both with and without ultrasound. We want to use 102 mice and expect a minimum distress for the animals. The experiments are performed under general anesthesia, and the animal will not recover consciousness, but be terminated after the experiments. The duration of the experiments is approximately 18 days.

In order to understand the behavior of nanoparticles in tissue it is not sufficient to only study the interactions between nanoparticles and single cells in vitro. Experiments using animals with intact blood vessels and normal tissue and tumor tissue are indeed needed.