Apigenin (Ap) is one of the most important natural flavonoids that has potent anticancer activity. This study was designed, for the first time, to load Ap into chitosan to improve its hydrophobicity and then it was coated with albumin-folic acid to increase its stability and bioavailability and to target cancer cells. The newly developed encapsulated Ap (Ap-CH-BSA-FANPs) was characterized and tested in vitro. The zeta potential of −17.0 mV was within the recommended range (−30 mV to +30 mV), indicating that encapsulated apigenin would not quickly settle and would be suspended. The in vitro results proved the great anticancer activity of the encapsulated apigenin on HePG-2 cells compared to pure Ap. The treated HePG-2 cells with Ap-CH-BSA-FANPs demonstrated the induction of apoptosis by increasing p53 gene expression, arresting the cell cycle, increasing caspase-9 levels, and decreasing both the MMP9 gene and Bcl-2 protein expression levels. Moreover, the higher antioxidant activity of the encapsulated apigenin treatment was evident through increasing SOD levels and decreasing the CAT concentration. In conclusion, the Ap-CH-BSA-FANPs were easy to produce with low coast, continued drug release, good loading capacity, high solubility in physiological pH, and were more stable than the formerly Ap-loaded liposomes or PLGA. Moreover, Ap-CH-BSA-FANPs may be a promising chemotherapeutic agent in the treatment of HCC.

New anticancer ruthenium(II/III) complexes [RuCl₂(DMSO)₂(Hapbim)] (1) and [RuCl₃(DMSO) (Hapbim)] (2) (Hapbim = 2-aminophenyl benzimidazole) have been synthesized and characterized, and their chemotherapeutic potential evaluated. The interaction of the compounds with DNA was studied by both UV-Visible and fluorescence spectroscopies, revealing intercalation of both the Hapbim ligand and the Ru complexes. The in vitro cytotoxicity of the compounds was tested on human breast cancer (MCF7), human colorectal cancer (Caco2), and normal human liver cell lines (THLE-2), with compound (2) the most potent against cancer cells. The cytotoxic effect of (2) is shown to correlate with the ability of the Ru(III) complex to induce apoptosis and to cause cell-cycle arrest in the G2/M phase. Notably, both compounds were inactive in the noncancerous cell line. The anticancer effect of (2) has also been studied in an EAC (Ehrlich Ascites Carcinoma) mouse model. Significantly, the activity of the complex was more pronounced in vivo, with removal of the cancer burden at doses that resulted in only low levels of hepatotoxicity and nephrotoxicity. An apoptosis mechanism was determined by the observation of increased Bax and caspase 3 and decreased Bcl2 expression. Furthermore, (2) decreased oxidative stress and increased the levels of antioxidant enzymes, especially SOD, suggesting the enhancement of normal cell repair. Overall, compound (2) shows great potential as a chemotherapeutic candidate, with promising activity and low levels of side effects.