Objective To prepare hyaluronic acid-modified polyphyllin VII-loaded metal-organic framework material IRMOF-10 targeted nanoparticles (HA@IRMOF-10@PPVII), systematically evaluate their physicochemical properties, safety and in vitro anti-triple negative breast cancer (TNBC) activity. Methods Metal-organic framework material IRMOF-10 was synthesized by triethylamine method. PPVII was encapsulated by the heterotopic encapsulation method, and the surface of the drug-loaded nanoparticles was modified with hyaluronic acid to construct the targeted nanoparticles HA@IRMOF-10@PPVII. The drug loading was determined by HPLC. The morphology, structure and thermal stability of nanoparticles were characterized by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TG) and BET specific surface area method. Its blood safety was evaluated by hemolysis test, and its cell targeting was verified by laser confocal microscopy. CCK-8, DAPI staining, Annexin V/PI double staining, migration assay, clone formation assay, cell uptake, reactive oxygen species (ROS) detection, mitochondrial membrane potential (MMP) detection and other methods were used to verify its inhibitory effect on TNBC 4T1 cells. Results The drug loading capacity of HA@IRMOF-10@PPVII was (39.56% ± 1.78)% (n = 3). HA@IRMOF-10@PPVII had good biosafety, which could significantly reduce the hemolysis risk of PPVII. This nanoparticle can effectively improve the uptake of PPVII in 4T1 cells, and significantly inhibits cell migration and clone formation. Its anti-tumor mechanism is closely related to inducing an increase in intracellular ROS levels, a decrease in MMP triggering apoptosis, and inhibiting the migration and cloning of 4T1 cells. Conclusion The HA@IRMOF-10@PPVII nanoparticles were successfully prepared, which exhibit excellent targeting ability and anti-TNBC activity. They can significantly enhance the efficacy of PPVII, providing experimental evidence for the development of PPVII-based anti-tumor formulations.

polyphyllin VII  /  metal organic framework materials  /  IRMOF-10  /  anti-tumor  /  triple negative breast cancer