Methotrexate and triformyl cholic acid functionalized magnetic graphene oxide nanocomposite for multi-targeting chemo-photothermal therapy of hepatocellular carcinoma

Abstract

Nano targeted therapy has been widely used in cancer treatment research by surface modification to increase the delivery of smart nanomedicine to specific target tissues, thereby reducing the toxic side effects of drugs on normal tissues. At present, a number of targeting ligands have been used for surface modification of nanomedicine, such as folic acid (FA) and hyaluronic acid (HA). Methotrexate (MTX), as a folic acid analog, has a strong tumor inhibition effect, which is expected to be used as a novel targeting ligand for tumor targeted therapy. However, the study of MTCATX as a nanomedicine carrier targeting ligand is rarely reported. And cholic acid is expected to be as a targeting ligand to liver cancer cells based on the specific binding effect of cholic acid on hepatocyte surface receptors. In addition, synergistic therapy has shown great potential in the treatment of hepatocellular carcinoma. Herein, a novel multi-targeting nano-drug carrier MGO-TCA-MTX (MTM) was constructed by functionalizing the surface of graphene oxide (GO) with Fe₃O₄, methotrexate (MTX) and triformylcholic acid (TCA) for synergistic chemo-phototherapy of hepatocellular carcinoma. The anti-tumor drug doxorubicin (DOX) was loaded onto nano-drug carrier MTM through hydrogen bonding and π–π stacking to form nanocomposite MGO-TCA-MTX@DOX (MTM@DOX) for enhanced chemo-photothermal therapy. The MTM@DOX with multiple tumor-targeting, near-infrared light (NIR) and pH triggered drug release, and high photothermal conversion efficiency exhibited an excellent tumor inhibitory effect on hepatocellular carcinoma in vitro and in vivo.