In Situ Insonation of Alkaline Buffer Containing Liposomes Leads to a Net Improvement of the Therapeutic Outcome in a Triple Negative Breast Cancer Murine Model

Breast cancer is characterized by an acidic micro-environment. Acidic extracellular pH gives cancer cells an evolutionary advantage, hence, neutralization of the extracellular pH has been considered as a potential therapeutic strategy. To address the issue of systemic pH alteration, an approach based on the targeted delivery of the buffering solution to the tumor region is investigated. The method relies on the use of low frequency ultrasound and sono-sensitive liposomes loaded with buffers at alkaline pH (LipHUS). After the i.v. injection of LipHUS, the application of ultrasound (US) at the sites of the pathology induces a local increase of pH that results highly effective in i) inhibiting primary tumor growth, ii) reducing tumor recurrence after surgery, and iii) suppressing metastases' formation. The experiments are carried out on a triple negative breast cancer mouse model. The results obtained demonstrate that localized and triggered release of bicarbonate or PBS buffer from sonosensitive liposomes represents an efficient therapeutic tool for treating triple-negative breast cancer. This approach holds promise for potential clinical translation. A method to deliver an alkaline buffer at the tumor site based on the use of sonosensitive liposomes andlocalized ultrasound application is reported. The increase of tumor extracellular pH induced by this therapeutic protocol strongly hampers the primary tumor growth, the formation of metastases, and the tumor recurrence after surgery in the triple negative breast cancer model.image

Automated summary

Breast cancer with acidic micro-environment can be treated by delivering alkaline buffers to the tumor region using sonosensitive liposomes. The increase of tumor extracellular pH induced by this approach effectively inhibits primary tumor growth, suppresses metastases' formation, and reduces tumor recurrence after surgery in a mouse model of triple negative breast cancer.