Ursolic acid loaded β-cyclodextrin/folic acid/Fe3O4 nanocomplex for drug delivery to tumor cells

The broad effects of ursolic acid (UA) on tumor cells have been demonstrated; however, due to its ineffective targeting properties and low level of water solubility, its clinical use is restricted. In this study, a novel drug carrier composed of β-cyclodextrin, UA, folate, and magnetic Fe3O4 nanoparticles (UA-β-CD-Fe3O4-FA-NPs) was prepared. TEM images showed that the synthesized NPs were spherical with a particle size in the range of 130–170 nm. The loading efficiency of UA in the nanocomplex was 58%, and drug release profiles proved the pH sensitivity of the nanocomplex. In vitro investigations on MCF-7 breast cancer cells indicated an antitumor activity of the nanocomplex (90%) at a concentration of 240 μg/ml after 48 h. In vivo studies were conducted on BALB/c mice-bearing breast cancer, and their survival rates, tumor volume, and weight were assessed. Results showed that the initial tumor size of untreated mice (350 mm3) reached the approximate final size of 450 mm3 in the untreated group, while it decreased to 300 mm3 in the nanocomplex-treated group and 200 mm3 in the group experiencing nanocomplex and the magnetic field treatment. Moreover, quantitative and qualitative drug accumulation tests performed using tumor iron concentration and histopathological images showed iron concentrations of 0.920 ± 0.032 and 0.540 ± 0.021 μg/g in the presence and absence of the magnetic field, respectively. The apoptogenic ability and removal of angiogenesis evaluated by P53 and CD31 antibodies also indicated that folate target and static magnetic field increased local UA concentrations in the tumor. These findings highlight the anticancer potential of this nanocomplex for further investigations.