TheraSonix · Ultrasonic Imaging and Drug Propulsion Into Tumors Using Genetically Encoded Gas Nanostructures

Ultrasonic Imaging and Drug Propulsion Into Tumors Using Genetically Encoded Gas Nanostructures

One of the important limitations of today's anti-cancer therapies is their inefficient and non-specific delivery—the systemic delivery of treatments like chemotherapy results in significant damage to healthy tissue and severe side effects. At the same time, most drugs have a limited penetration depth of only a few cell layers into the tumor. These drugs are concentrated around the heterogeneous vasculature and produce only a local therapeutic effect. In this project, we proposed a method of overcoming these limitations by using focused ultrasound for selective activation of targeted bio-molecules and tumor homing cells. The resulting vibrations can locally release anti-cancer drugs and deliver them deep into the tumor core. The proposed approach is based on ultrasonic cavitation, a phenomenon in which gas bubbles expand and collapse under the influence of ultrasound waves. This process produces fluid streaming that propels drugs deeper into the tumor mass. The use of ultrasound for drug delivery is attractive due to its availability and affordability. However, the use of this technology is currently limited by the properties of conventional microbubble-based cavitation nuclei: their large size prevents them from penetrating into the tumor, and their short circulation times do not match the pharmacokinetic time constants of many drugs. To overcome these challenges, we will utilize gas vesicles (GVs), a unique class of genetically encoded, gas-filled protein nanostructures, as cavitation nuclei. In nature, GVs are used by buoyant photosynthetic microbes that use them to regulate their flotation. Unlike microbubbles, GVs are physically stable. Their nanoscale dimensions have the potential to enable them to extravasate into tumors and bind to specific cellular targets. Recently our lab was able to express GVs in tumor-homing bacteria and mammalian cells and use their acoustic signature as a deep-tissue reporter of gene expression. We hypothesized that GVs could act as both imaging agents and cavitation nuclei. This therapeutic approach could provide vastly improved efficacy and selectivity and the potential to combine cavitation-enhanced drug delivery with emerging advancements in cell-based therapeutics.

Data: CORDIS, © European Union