Objective To prepare diosgenin silk fibroin nanoparticles (Doi-SF-NPs) and evaluate their physicochemical properties, tumor targeting and in vivo anti-tumor effects . Methods The main influencing factors of Doi-SF-NPs were investigated by single factor experiments, and Box-Behnken design-response surface methodology (BBD-RSM) was employed to optimize prescription process of Doi-SF-NPs. Doi-SF-NPs was characterized by transmission electron microscopy (TEM) and Fourier transform infrared spectroscopy (FT-IR). Drug release behavior of Doi-SF-NPs in phosphate buffer saline solution with different pH values was investigated. MTT method and Annexin V/PI double staining method were used to investigate the inhibitory and proapoptotic effects of Doi-SF-NPs on PC3 cells, respectively. The nude mouse of prostate cancer was established, compared the concentrations of diosgenin and Doi-SF-NPs in tumor tissues, and then evaluated the tumor targeting ability of Doi-SF-NPs using the relative uptake rate and ratio of peak concentration. The nude mouse model of prostate cancer was divided into model (normal saline) group, positive control (cisplatin, 2.0 mg/kg) group, diosgenin (10 mg/kg) group, low-dose Doi-SF-NPs (5 mg/kg) group and high-dose Doi-SF-NPs (10 mg/kg) group, the in vivo anti-tumor effects of Doi-SF-NPs was compared with diosgenin. Safety evaluation of Doi-SF-NPs was also performed. Results Optimal prescription process of Doi-SF-NPs nanoparticles as follows: The mass ratio of silk fibroin to diosgenin was 11.94:1, the volume ratio of the organic phase to aqueous phase was 5.99:1, and the preparation time was 2.75 h. Average envelopment efficiency, drug loading, particle size and ζ potential were (84.07 ± 0.70)%, (6.41 ± 0.05)%, (164.29 ± 4.43) nm and (−23.01 ± 1.17) mV, respectively. Diosgenin formed Doi-SF-NPs with silk fibroin through hydrogen bonding. The appearance of Doi-SF-NPs was spherical nanoparticles. Doi-SF-NPs existed higher cumulative release in phosphate buffer solution of pH 5.5 and 6.0, which demonstrated that Doi-SF-NPs had obvious pH-sensitivity. MTT method results showed that IC₅₀ of diosgenin and Doi-SF-NPs on PC3 cells were 72.44 and 55.68 μmol/L, respectively. Doi-SF-NPs more effectively induced apoptosis of PC3 cells than that of diosgenin. The relative uptake rate of Doi-SF-NPs in in tumor tissue was 3.23, and the peak concentration ratio was 2.60, which demonstrating that Doi-SF-NPs could significantly increase the accumulation in tumor tissue. Doi-SF-NPs (10 mg/kg) increased the tumor inhibition rate of diosgenin (10 mg/kg) from 29.47% to 66.18%. Doi-SF-NPs did not affect the major organs of tumor-bearing nude mouse, which showed that the safety of Doi-SF-NPs was high. Conclusion Doi-SF-NPs could improve the tumor targeting of diosgenin and significantly enhanced anti-tumor efficacy. Therefore, Doi-SF-NPs had the potential to be developed into an antitumor drug.

diosgenin  /  silk fibroin  /  nanoparticles  /  Box-Behnken design-response surface methodology  /  prostate cancer  /  tumor targeting  /  anti-tumor  /  safety evaluation