A new method that uses sound waves to release chemotherapy in lymph nodes invaded by breast cancer cells could offer a safer option to other, more invasive techniques, according to results from a mouse study.
Researchers at Tohoku University in Japan created small vesicles, or hollow beads, filled with chemotherapeutic agents that burst upon contact with sound waves. The vesicles were injected into the mice’s lymphatic systems, traveling to the affected lymph nodes. When high-intensity ultrasound was applied to the armpit, the vesicles ruptured, releasing the medicines in a targeted manner.
The approach effectively killed breast cancer cells in the lymph nodes without damaging the lymphatic vessels and with minimal systemic toxicity, the researchers said.
The study, “Use of a Lymphatic Drug Delivery System and Sonoporation to Target Malignant Metastatic Breast Cancer Cells Proliferating in the Marginal Sinuses,” was published in the journal Nature.
In the advanced stages of breast cancer, malignant cancer cells can enter the lymphatic vessels and establish metastasis in the lymph nodes. From there, the cells can travel through the lymphatic system and spread the cancer to distant regions of the body.
Treating affected lymph nodes is crucial, but techniques such as surgery, radiation, and chemotherapy can be highly invasive and lead to severe adverse events, which may cause patients to discontinue treatment.
These were injected into a lymph node in the mouse’s pelvic area, and migrated to the lymph nodes under the front limb. A high-intensity ultrasound was then applied, causing the vesicles to burst and release the medicine directly to the site of the cancer.
The type of breast cancer cells used in the experiments were little invasive — meaning they were mostly contained in the breast and did not spread to other regions — and had well-defined borders.
So the team chose to repeat the work using a highly invasive type of breast cancer cells — known as the FM3A murine (mouse) breast cancer cell line — that is difficult to treat in lymphatic tissue.
The researchers devised a control experiment in which empty vesicles were injected in the pelvic lymph nodes of mice to determine whether they reached the breast lymph nodes. Using ultrasound and 3D imaging to follow the vesicles, they found that vesicles successfully traveled to the lymph nodes under the arm and remained in place.
The vesicles were then tested in mice injected with the FM3A cells to mimic breast cancer that had spread to the lymph nodes. Mice were divided into three groups: one group receiving a control saline solution; one given vesicles filled with doxorubicin, a known anticancer agent, but not ultrasound; and one given the chemo-filled vesicles with low- or high-intensity ultrasound under the front limbs.
A bioluminescence technique in which a high signal represented greater tumor volume was used to track tumor growth over time.
In mice treated with saline or doxorubicin-filled vesicles alone, the bioluminescent signal increased over the 10 days of the experiment, indicating that the tumor was growing.
A smaller increase in tumor growth was seen in the group treated with vesicles plus low-intensity sound. However, when given high-intensity sound, the bioluminescence signal did not increase or increased very little over the 10-day period, indicating a suppression of tumor growth.
The lymph nodes were removed and examined under a microscope for cancer cell growth. FM3A cell growth was evident in the mice that had been treated with saline or doxorubicin-filled vesicles alone, while tumor cell growth was not observed in the areas of the lymph nodes in mice treated with high-intensity sound.
“We conclude that lymphatic administration of a drug combined with [ultrasound] could exert a curative effect in [lymph nodes] containing metastatic cells,” the researchers wrote.
“We believe that our technique has the potential to be developed into a new treatment for lymph nodes invaded by metastatic tumour cells,” Tetsuya Kodama, PhD, who led the study, said in a press release.