Ultrasound Remotely Bursts Heat-Sensitive Capsules, Supplying Drugs Directly to Tumors

An encouraging new cancer drug delivery system has successfully passed initial human safety trials. The treatment carries cancer drugs in heat-activated capsules to tumors in the liver and then uses a focused ultrasound beam to remotely trigger the targeted release of their drug payload.

The first-of-its-kind treatment involves injecting a patient with heat-sensitive, chemotherapy-filled lipid capsules. A beam of focused ultrasound is then directed at the tumor, which in these trials were located in the liver. The ultrasound slightly increases the temperature of the tumor to above 39.5° C (103° F), which is the temperature the lipid capsules are engineered to release their payload. This means the drug is ultimately delivered straight into the tumor in amplified concentrations.

"Reaching therapeutic levels of cancer drugs within a tumor, while avoiding side effects for the rest of the body is a challenge for all cancer drugs, including small molecules, antibodies and viruses," says Constantin Coussios, Director at Oxford Institute of Biomedical Engineering. "Our study is the first to trial this new technique in humans, and finds that it is possible to safely trigger and target the delivery of chemotherapy deep within the body using focused ultrasound."

This trial evaluated the safety of this untried treatment in 10 patients, and outside of the standard general anesthetic and chemotherapy side effects, there were no added risks or consequences found to stem from this new method. Taking tumor biopsies from each patient following the treatment identified a rather large variety of chemotherapy concentrations. On average, the amount of chemotherapy found inside the tumor was around 3.7 times higher, compared to before ultrasound exposure.

Three patients did display minor increases in chemotherapy concentrations, and the researchers hypothesize that this variability is most likely due to ultrasound-induced heating variations from patient to patient. Further research to better target the ultrasound beams is essential, although it is reasonably clear that the treatment certainly increases direct chemotherapy concentrations in targeted tumors.

Dieter Haemmerich Ph.D., D.Sc., from the Medical University of South Carolina, published an external commentary of the research in the journal The Lancet and described this study as an important step in demonstrating an elegant targeted drug delivery approach. Haemmerich also noted this method could be broadly applicable to a variety of solid tumors.

"Although the investigators showed the safety, feasibility, and therapeutic potential of lyso-thermosensitive liposomal doxorubicin (LTLD) in patients with liver cancer, the described focused ultrasound plus LTLD approach might be more widely applicable to other solid tumors because doxorubicin is a wide-spectrum antitumor drug," concludes Haemmerich.

The complete research was published in The Lancet.

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