Background: Despite improved knowledge on cancer prevention, progression, and treatment, the incidence of cancer is still increasing. Patients with highly aggressive triple-negative breast cancer benefit from chemotherapy as the only systemic therapeutic alternative. Here, we performed studies that demonstrate the effects of trastuzumab linked to nanostructures with pH-dependent release on triple-negative models. Methods: We assessed in vitro cell proliferation, migration, invasion, mammospheres, spheroids, and organoid formation of human and murine cell lines. Balb/c mice were used to investigate the in vivo anti-tumoral effects of functionalized nanostructures. Ex vivo samples and cell lines were used to investigate, using immunohistochemistry and Western blot, the modulation of key molecular pathways. Results: Using a human normal cell line and human and murine triple-negative breast cancer cell lines, we found that trastuzumab exhibits anti-tumoral properties on triple-negative breast cancer cell lines only when linked to pH-sensitive micelles. In addition, the data demonstrates that functionalized micelles induce mesenchymal-to-epithelial transitions, impairing the metastasis. Conclusions: Taken together, these results indicate that functionalization of micelles by linking trastuzumab may open the way of treating triple-negative patients with trastuzumab, a treatment which is currently in use for patients with Her2 overexpression. The functionalized micelles may be loaded with various molecules to further improve the anti-tumoral effects.
Keywords: EMT; TNBC; drug delivery system; targeted delivery; trastuzumab.