Scientists develop new therapy for ultrasound-guided microbubbles

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In recent years, breast cancer has become a major killer of women's health. In 2020, breast cancer in women surpassed lung cancer for the first time as one of the most common cancers worldwide. In China, breast cancer is the most common malignant tumor in women. After surgery for early breast cancer, about 30% may eventually develop into advanced breast cancer. Under the current medical technology, advanced breast cancer is difficult to treat, and the overall survival time of patients is short.

Immunotherapy has transformed breast cancer treatment, but not all patients respond to immune checkpoint blockade. To this end, researchers at the University of Texas Southwestern Medical Center developed a microbubble-assisted ultrasound-guided cancer immunotherapy (MUSIC). This therapy can not only effectively deliver therapeutic drugs to cells to generate systemic anti-tumor immunity, but also improve the therapeutic effect of immune checkpoint blockade in breast cancer.

MUSIC uses a combination of ultrasound and microbubbles, injecting tumors in tiny gas-filled bubbles and detonating them using ultrasound, causing mechanical pressure to remove the cancer cells.

Specifically, the microbubbles oscillated when exposed to an ultrasonic field. If these microbubbles bind to cells when the ultrasonic intensity is high enough, the oscillations pull the cell membranes into motion. This creates pores that open the door for microvesicle drugs to enter the cell membrane. That is, instead of killing cancer cells with brute force, the technology uses ultrasound to make small openings in the cell membrane for drugs to enter.

cGAMP is a natural agent capable of triggering an immune response against tumors by activating the cGAS-STING pathway. But delivery methods for cGAMP have been hampered by poor stability and slow entry into cells. The researchers used microbubbles to load cGAMP, which was able to penetrate antigen-presenting cells (APCs) more efficiently and activate the cGAS-STING pathway due to ultrasound-induced cell membrane oscillations. This, in turn, fuels an attack by immune T cells, which then target and destroy the tumor cells.

In experiments with breast cancer in mouse models, the MUSIC strategy showed a 60% complete tumor eradication rate. When combined with anti-PD-1 antibodies, MUSIC significantly improved antitumor responses and also generated antitumor memory in T cells, preventing tumor recurrence. In addition, this combination therapy resulted in an average survival rate that was 76% higher than that of PD-1 blockade alone, compared to treatment alone.

In the future, I hope this technology can bring good news to breast cancer patients.