In a new paper in The Journal of Clinical Investigation, Katherine W. Ferrara, PhD, and her team at UC Davis report their strategy to destroy an entire tumor without thermal destruction of the tumor margin. Her group used focused ultrasound to dramatically increase the concentration of doxorubicin within several types of tumors using mouse models of mammary carcinoma.
Ferrara’s previous research showed that ultrasound-induced mild hyperthermia could enhance the accumulation of doxorubicin-loaded nanoparticles in a tumor, but the accumulation was dependent on the type of tumor. Her group hypothesized that combining thermal ablation and chemotherapy could improve efficacy across multiple types of tumors.
As the focused ultrasound damaged the tumor and induced a local immune response, nanoparticles accumulated in the tumor and the local drug concentration increased 50-fold. The high drug concentrations continued over several weeks, increasing total exposure of the tumor to the drug. The enhanced drug accumulation resulted in improved survival and a consistent cure in their preclinical model of breast cancer, even when only a portion of the tumor was ablated.
They also demonstrated that an effective cure could be achieved with a carefully designed protocol involving heat-activated nanoparticles, which, when gently heated by ultrasound, release their chemotherapeutic payload in the vasculature surrounding the tumor.
Source: UC Davis