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

Author:

Patrucco Deyssy1,Cutrin Juan Carlos1,Longo Dario Livio2,Botto Elena2,Cong Li3,Aime Silvio4ORCID,Delli Castelli Daniela1

Affiliation:

1. Department of Molecular Biotechnology and Health Science University of Turin Via Nizza 52 Turin 10126 Italy

2. Istituto di Biostrutture e Bioimmagini (IBB) Consiglio Nazionale delle Ricerche (CNR) Via Tommaso De Amicis, 95 Naples 80145 Italy

3. Key Laboratory of Smart Drug Delivery Ministry of Education School of Pharmacy Fudan University Shanghai 201203 China

4. IRCCS SDN SYNLAB Via Gianturco 113 Naples 80143 Italy

Abstract

AbstractBreast 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.

Funder

National Natural Science Foundation of China

Innovative Research Group Project of the National Natural Science Foundation of China

Publisher

Wiley

Subject

Pharmaceutical Science,Biomedical Engineering,Biomaterials

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