Bovine serum albumin-bound homologous targeted nanoparticles for breast cancer combinatorial therapy

Breast cancer, the most common lethal cancer among women, is characterized by the uncontrolled growth of abnormal cells in breast tissue. Therefore, synergistic anticancer strategies are essential, particularly for maximizing drug delivery to tumor sites. Herein, bovine serum albumin (BSA)-bound nanoparticles encapsulating the photosensitizer chlorin e6 (Ce6) (BC) with a CuO₂ core (BC/CuO₂ NPs) were developed for cuproptosis-promoted cancer photodynamic therapy (PDT). The cancer cell membrane (CC) was then coated onto the surfaces to produce BC/CuO₂@CC NPs for breast cancer combinatorial therapy. BSA serves dual functions as both a stabilizing scaffold for metal peroxide nanomaterials and a molecular connector for Ce6. The BC/CuO₂@CC NPs group showed the stronger internalization capability than the other groups. BC/CuO₂@CC NPs could effectively induce the greatest degree of apoptosis and death ratio (81.77 %), and lead to cuproptosis by downregulating the expression of DLAT, LIAS, and FDX1 protein in vitro. The intra-tumoral accumulation of BC/CuO₂@CC NPs was 8.3- and 7.7-fold higher than that of Ce6 and BC/CuO₂@CC NPs at 24 h postinjection, respectively. Moreover, synergistic efficacy of cuproptosis and PDT not only inhibited tumor growth but also prevented liver metastases. Thus, our work may be a novel approach for efficient and targeted cancer treatment.