Boosting Cuproptosis in Breast Cancer Therapy via Photodynamic Treatment With a New Liposome.

Breast cancer (BC) is one of the most common cancers in women around the world, and utilizing a combined approach is a crucial strategy. Induction of cuproptosis in tumor cells is a novel antitumor approach, though its standalone efficacy remains unclear. In this study, we prepared a novel liposome loaded with the photosensitizer indocyanine Green (ICG) and the cuproptosis inducer elesclomol-Cu (ES-Cu) to examine the synergistic effects of photodynamic-cuproptosis treatment on BC. The cuproptosis inducer ES-Cu and the photosensitizer ICG were encapsulated in nanoliposomes with a membrane hydration approach and then validated in vitro and in vivo. JC-1, MDA, GSH, and other cuproptosis-related indicators were used to confirm the ability of PDT to enhance ES-Cu-induced cuproptosis in MCF-7 breast cancer cells. For confirming the cytotoxic impact of PDT in conjunction with the cuproptosis inducer, tests for CCK-8 and cell death staining were performed. The drugs were administered to animals via tail vein injection to observe their tumor inhibition effects in vivo. Their safety was assessed by monitoring changes in body weight. The average particle size of liposomes loaded with ES-Cu and ICG was 208.3 ± 1.07 nm, exhibiting a consistent nanospherical morphology. ICG produced cytotoxic reactive oxygen species (ROS) that enhanced ES-Cu-induced cell cupping under NIR laser irradiation. The therapeutic effect of the synergistic treatment combining PDT and cuproptosis was validated in both in vitro and in vivo experiments. This investigation proved that PDT markedly augments the ES-Cu-induced cuproptosis in breast cancer cells, demonstrating a synergistic therapeutic effect. This synergistic effect presents a novel therapy approach for BC with substantial practical application potential.