Application of ultrasound and microbubbles to facilitate immunotherapy
Gas microbubbles, coated with a surfactant or polymer shell, are an effective type of contrast agent for diagnostic ultrasound imaging. The gas cores of the microbubbles scatter ultrasound more efficiently and over a wider range of frequencies than blood cells, producing a strong contrast between the vasculature and the surrounding tissue.
It has been shown that microbubbles can also be used for the targeted delivery of drugs by incorporating them into the encapsulating shell of the microbubbles. The microbubbles can then be introduced into the body at their intended site of action or injected intravenously and their passage through the bloodstream can be traced using low-intensity ultrasound imaging.
Once the microbubbles have reached their intended location, the drug can be released by increasing the ultrasound intensity to rupture the microbubbles selectively. It has been shown that the rupture of the microbubbles may also enhance the cellular uptake of the drug.
Delivering proteins to the cell membrane in a controlled fashion has proven extremely challenging in the development of cancer immunotherapies; requiring complex ex vivo procedures. Oxford researchers address this challenge by engineering microbubbles’ with surface membrane proteins incorporated into their lipid shell that can transfer them to a target cellular membrane in a controlled fashion under ultrasound exposure. Importantly the approach has the potential to be applied in vivo as both ultrasound and microbubbles are widely used in ultrasound imaging and have recently been trialled clinically to promote the diffusion of chemotherapy drugs into tumours.
The main advantage of the technology is that it provides a way to deliver proteins onto the cellular membrane, rather than into the cells, a process proven to be extremely difficult until now. Furthermore, it potentially allows for modulation of the immune response in vivo, providing a non-invasive, selective alternative to conventional cancer treatments, such as surgery, radiotherapy and chemotherapy.
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