Bacterial magnetosomes loaded with doxorubicin and transferrin improve targeted therapy of hepatocellular carcinoma

摘要

High metastatic rate and recurrence of tumor because of tumor circulating cells are seriously hinders for clinical tumor therapy. Herein, we develop a novel, active>-targeting nanotherapeutic by simultaneously loading doxorubicin (DOX) and transferrin (Tf) onto bacterial magnetosomes (Tf-BMs-DOX) and investigate its antitumor efficacy in vitro and in vivo. Drug release profiles indicated that Tf-BMs/BMs loaded with DOX were capable of sustained drug release, suggesting that reduce drugs required frequency of administration and enhance their therapeutic effect. The results of cellular uptake revealed that Tf-BMs-DOX recognized hepatocellular carcinoma HepG2 cells more specifically compared to HL-7702 normal hepatocytes because of high expression of transferrin receptor (TfR) on the surface of HepG2 cells. Tf-BMs-DOX increased tumor cytotoxicity and apoptosis more significantly than free DOX or BMs-DOX by regulating the expression of tumor>-related and apoptosis>-related genes. Following intravenous injection in HepG2 cell>-bearing mice, Tf-BMs-DOX displayed tumor suppression rate of 56.78%, significantly higher than that of the BMs-DOX (41.53%) and free DOX (31.26%) groups. These results suggest that Tf-BMs-DOX have the potential to actively target to tumor sites, as well as the ability to kill circulating tumor cells via intravenous injection. Our findings provide a promising candidate for the clinical treatment of metastatic cancer.