Construction of self-assembled rhein–methotrexate nanoparticles and study of their synergistic anti-breast cancer mechanism

Abstract

The treatment of breast cancer, as a common malignant tumor in women, still faces challenges such as low drug delivery efficiency and significant toxic side effects. Based on the hydrogen bonds and hydrophobic interactions between rhein (Rhe) and methotrexate (MTX), in this study, a carrier-free self-assembled nanomedicine (MR) was designed and prepared. The nanomedicine exhibits a uniform spherical structure, high drug loading capacity and excellent in vitro stability. Cell experiments showed that MR demonstrated significantly enhanced cellular uptake in MCF-7 cells relative to free drugs. Moreover, MR induced mitochondrial structural damage and a decrease in membrane potential, indicating that it can induce cellular dysfunction through the mitochondrial pathway. Further studies found that MR significantly inhibited the proliferation and migration of MCF-7 cells, promoted their apoptosis in a dose-dependent manner, and exhibited anti-tumor activity that was significantly superior to that of MTX or Rhe alone and their physical mixture. In summary, the carrier-free self-assembled nanosystem developed in this research not only provides a robust platform for the effective delivery of hydrophobic natural compounds, but also provides an experimental basis for the development of synergistic chemotherapy strategies for breast cancer.