The effect of ultrasound on the extracellular matrix (ECM) for drug delivery in solid tumors

Proper understanding of the impact of various ultrasound exposure parameters on drug delivery is important when designing the optimal ultrasound treatment protocol for improved delivery of nanoparticles (NPs) or drugs in solid tumors. This is because the various effects of ultrasound has on drug delivery maybe optimal at different exposure parameters. The effect of ultrasound on the extracellular matrix (ECM) i.e collagen will be investigated by applying ultrasound and microbubbles to a solid tumor grown in fat pad when microbubble and NPs are circulating.The collagen and NPs will be imaged in real time using multiphoton microscopy imaging the collagen fibers with the second harmonic generated (SHG) signal.This imaging method is the only one that provides high enough spatial resolution that can distinguish the change in the collagen structure, content, and orientation with and without ultrasound. We want to use maximum 100 mice and expect a minimum distress for the animals. The treatments are performed under general anesthesia. The duration of the experiments is approximately 30 days. In order to understand the effect of ultrasound on the the ECM, it is not sufficient to only study the interactions between ultrasound on the collagen network in vitro without having a circulating microbubbles. Experiments using animals with intact blood vessels as well as fully developed ECM both in normal tissue and tumor tissue are indeed needed.