Focused Ultrasound Helps Sono-Sensitized Chemotherapy Reach and Treat Deep Tumors


Key Points

  • Researchers in Hong Kong developed an anti-cancer platinum prodrug called cyaninplatin and then showed that focused ultrasound could activate it.
  • The team also conducted preclinical studies to deliver sono-sensitized chemotherapy to deep tumors.

An Ultrasound-Activatable Platinum Prodrug for Sono-Sensitized Chemotherapy

Schematic illustration of the working mechanism of cyaninplatin. Cyaninplatin can execute cancer cell killing and multimodal imaging guided sono-sensitized chemotherapy (SSCT) upon activation by focused ultrasound (FUS). i.v., intravenous.

Source: Gongyuan Liu et al., An ultrasound-activatable platinum prodrug for sono-sensitized chemotherapy.Sci. Adv.9,eadg5964(2023).DOI:10.1126/sciadv.adg5964

To improve the delivery of chemotherapy to deeper tumors, a collaborative group of researchers based at City University of Hong Kong developed an anti-cancer platinum prodrug called cyaninplatin, and then showed that focused ultrasound could activate it within target lesions. Platinum (Pt) prodrugs have recently been used for diagnosing and treating disease, but the understanding of how mechanical forces activate metal-based anticancer agents is lacking.

After developing cyaninplatin, the research team used focused ultrasound to convert it to carboplatin, a common chemotherapy drug, and presented data on potential mechanisms of the required chemical reaction. This precise and spatiotemporally controlled technique activates the cyaninplatin to damage mitochondria, which depletes intracellular reductants and induces bursts of reactive oxygen species, all of which may contribute to cell damage and death.

Importantly, the prodrug also acts as a multi-imaging contrast agent, allowing for real time guidance with high-resolution ultrasound, near-infrared optical imaging, and photoacoustic CT. Interestingly, the sono-activated cyaninplatin also evoked an immune response by recruiting and activating T cells.

For these experiments, the researchers designed a custom, ultrasound-guided focused ultrasound system in their laboratory. The system has integrated components from Sonic Concepts and Verasonics.

The authors concluded that the use of sono-sensitized chemotherapy increased their ability to visualize and treat deep tumors: In Ex vivo and in vivo tests, the technology successfully activated cyaninplatin with a centimeter range of tissue depth. These findings have great potential for clinical translation.

Focused Ultrasound Turns Chemo from Shotgun Blast to Sniper Shot, an article about this research in New Atlas, said “When fighting cancer, chemotherapy is still a bit of a blunt instrument. By combining it with soundwaves, however, researchers have found a way to turn it into more of a scalpel than a club, sparing damage to nearby tissue and the body as a whole.”

See Science Advances (open source)

See New Atlas