Our previous studies have proven that
carnosic acid (CA) induces apoptosis of
liver cancer cells. However, the poor chemical properties of CA limit its in vivo anti-
cancer effects. In this study, CA was loaded into
liposomes (LP-CA), and LP-CA was further conjugated with
transferrin (Tf-LP-CA) to overcome the shortcomings of poor solubility and absorption at the lesion site. In HepG2 and SMMC-7721 cells, compared with CA and LP-CA, more Tf-LP-CA was absorbed by
liver cancer cells, which induced higher levels of apoptosis and reduced the mitochondrial membrane potential more effectively. In HepG2- and SMMC-7721-xenotransplanted mice, Tf-LP-CA inhibited
tumor growth with no cytotoxicity to the liver, spleen, or kidney. Furthermore, compared with CA and LP-CA, Tf-LP-CA targeted the
tumor site more effectively, enhanced the expressions of cleaved
poly(ADP-ribose) polymerase, and
Caspase-3 and -9, and regulated the expression levels of
B-cell lymphoma 2 (Bcl2) family members in the
tumor tissues. Tf-LP-CA was taken up by
tumor cells and targeted at
tumor tissues, ensuring the precise delivery of CA, which further promoted mitochondria-mediated intrinsic apoptosis in the
liver cancer cells. These results provide evidence for the clinical application of the Tf-LP-based CA drug delivery system for
liver cancer.