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 give 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 tumour region has been 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 induce a local increase of pH that resulted highly effective in i) inhibiting primary tumor growth, ii) reducing tumor recurrence after surgery, and iii) suppressing metastases' formation. The experiments were 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. This article is protected by copyright. All rights reserved.