Microbubbles for Ultrasound-Mediated Cancer Treatment (BubbleCAN)

This project addresses the optimization of a product rendering the delivery of very high local concentrations of drugs to tumors using non-invasive focused ultrasound possible. The product is based on SINTEF owned technology platforms. With traditional chemotherapy typically only 0.001-0.01% of the injected dose reaches the tumor. The remaining drug leads to severe side effect on healthy cells and tissue. Focused ultrasound in combination with tiny gas bubbles applied directly at the tumor has been shown to increase the transport of drugs locally to the tumor by forming small pores in the blood vessels surrounding the tumor. However, commercially available gas bubbles are optimized for ultrasound imaging, being fragile and unstable in blood. There is a clear need for a novel drug delivery system based on stable gas bubbles specifically designed for ultrasound-mediated drug delivery applications. Currently, there are no such products on the market. The main goal of BubbleCAN is to optimize such a product towards commercialization. The uniqueness of the BubbleCAN product is its simplicity and versatility, combining drug-loaded nanoparticles and bubbles in one single construct. The aim of the BubbleCan project is to make long-circulating drug-loaded bubbles to be used in cancer treatment. Nanoparticles loaded with anti-cancer agents will be used to form a shell around gas bubbles. The nanoparticle-stabilized bubbles are injected into the blood stream. When they enter the tumor site, the ultrasound waves applied at the tumor lead to bubble collapse, formation of small pores in the blood vessels, and release of individual nanoparticles. The drug-loaded nanoparticles accumulate in tumor tissue and slowly release the drug. The BubbleCAN product is relevant for tumors that are not effectively treated using existing chemotherapeutic technology, e.g. inoperable solid tumors and gliomas. We have now performed the first proof-of-principle studies in mice. We have shown that we get 250 times higher concentration of a model-drug into tumor tissue when treated with the BubbleCAN technology as compared to model-drug alone. Further, an enhanced therapeutic effect has been demonstrated in mice, where all tumors showed regression into complete remissimion after treatment with the BubbleCAN technology. We have also worked on optimizing the ultrasound parameters, and will use these results in a large study in mice for treatment of prostate cancer with the BubbleCAN technology.

For SINTEF: Prosjektet har vært essensielt for å bygge kompetanse rundt teknologien og dens virkning og muligheter. Vi har vist at teknologien har et stort potensial for behandling av kreft og lært hva slags effekter vi kan forvente ved bruk av denne teknologien. De gode resultatene fra prosjektet har ført til mye publisering. For TTO/kommersialisering: Prosjektet har vært avgjørende for optimalisering av BubbleCAN teknologiplattformen og tatt teknologien flere skritt nærmere en mulig kommersiell utnyttelse. Vi har fått avklart hvilke suksessfaktorer som er kritiske for kommersialisering. For brukere/samfunnet: En ny teknologi for forbedret behandling av kreft med færre bivirkninger har stor samfunnsverdi og samfunnsinteresse. Resultater fra prosjektet kan også brukes mot utvikling av teknologien mot andre sykdommer og gagne nanomedisinfeltet generelt.

This project addresses the optimization of a product rendering the delivery of very high local concentrations of drugs to tumors using non-invasive focused ultrasound (US) possible. The product is a single construct of gas-filled microbubbles (MBs) stabilized by drug-loaded nanoparticles and is relevant for tumors that are not effectively treated using existing chemotherapeutic technology, e.g. inoperable solid tumors and gliomas. The product is based on SINTEF owned technology platforms and has been partly validated in the lab. With traditional chemotherapy typically only 0.001-0.01% of the injected dose reaches the tumor. Focused US in combination with MBs applied directly at the tumor site can facilitate the transport of drugs by locally increasing the vascular permeability. However, commercially available MBs are optimized for US-imaging, having a very thin and fragile shell and short blood circulation time. There is a clear need for novel drug-loaded MBs with a high drug payload, specifically designed for US-mediated drug delivery applications. Currently, there are no such products on the market. The main goal of BubbleCAN is to optimize such a product towards commercialization. The uniqueness of the BubbleCAN product is its simplicity and versatility, and an initial literature and patent search confirms the novelty and high possibility to build a strong IP platform. The success of the project relies on making long-circulating drug-loaded MBs tailor-made for US-mediated delivery of anti-cancer agents, showing superior therapeutic properties compared to existing drug-delivery technology. At the end of the project we anticipate that the technology platform will have reached TRL5 and will be ready for the development of defined prototypes. Customers of BubbleCAN technology are SMEs and big pharma looking for novel delivery techniques for their anti-cancer agents. The ultimate end-users of BubbleCAN products are physicians and their patients suffering from cancer.