Objective A targeted nanoformulation (PEG-PTP/PPVI@IRMOF-1) was constructed by encapsulating the traditional Chinese medicine antitumor active component polyphyllin VI (PPVI) within isoreticular metal-organic framework-1 (IRMOF-1) and coating it with a cell-penetrating peptide. The study aims to characterize the nanoformulation and conduct a preliminary evaluation of its in vitro antitumor efficacy. Methods PEG-PTP/PPVI@IRMOF-1 was fabricated via the “triethylamine precipitation method” and “reaction coating method”; The physicochemical properties of the nanoformulation, including particle size, morphology, thermal stability, and specific surface area, were characterized by particle size and ζ-potential measurement, scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), Brunauer-Emmett-Teller (BET) gas adsorption, and X-ray photoelectron spectroscopy (XPS). Hemolysis assay was used to assess the biosafety of nanomaterials. CCK-8 assay was adopted to evaluate the material safety and detect the effect of nanoparticles on the proliferation of human pancreatic cancer PANC-1 cells. The effect of materials and nanoparticles on the nuclear morphology of PANC-1 cells was observed by fluorescence microscopy; The targeting capability of the nanoparticles ex vivo was assessed by laser scanning confocal microscopy; The effects of nanoparticles on cell proliferation and migration were examined using colony formation and scratch assays, respectively; Flow cytometry was employed to determine the impact of the nanoparticles on the cellular apoptosis rate and intracellular reactive oxygen species (ROS) levels; The effect of nanoparticles on the mitochondrial membrane potential (MMP) of cells was examined by laser confocal microscopy. Results The targeted nanoformulation PEG-PTP/PPVI@IRMOF-1 was successfully fabricated as a dry white powder. The nanoparticles exhibited a quasi-spherical morphology with an average particle size of about (177.47 ± 3.97) nm and a ζ potential of (−7.94 ± 0.14) mV; The drug loading capacity (DLC) of PPVI@IRMOF-1 was (43.02 ± 0.08)%; The nanomaterial showed excellent biocompatibility; Notably, targeted peptide modification can significantly enhance the drug uptake of tumor cells, significantly inhibit cell proliferation, promote the production of ROS and the decrease of MMP in cells, and induce apoptosis of tumor cells. Conclusion The prepared PEG-PTP/PPVI@IRMOF-1 nanoparticles possess uniform morphology, high drug loading capacity, and good biocompatibility. Moreover, the nanoformulation significantly enhances the in vitro antitumor efficacy of PPVI, providing a reference for the development of PPVI-based antitumor formulations.

polyphyllin VI  /  metal-organic framework materials  /  targeted nanoformulation  /  anti-tumor  /  pancreatic cancer