Bimodal Treatment of Hepatocellular Carcinoma by Targeted Minimally Interventional Photodynamic/Chemotherapy Using Glyco-Covalent-Organic Frameworks-Guided Porphyrin/Sorafenib

Abstract

Very limited treatment options are available to fight hepatocellular carcinoma (HCC),  a serious global health concern  with high morbidity and mortality. The integration of  m ulti ple  therapies into one nanoplatform to exert synergistic therapeutic effects offers advantages over  monotherapies. Here,  we describe the construction of the nanoplatform Sor@GR-COF-366for synergistic chemotherapy and photodynamic therapy (PDT)  for HCC  using a porphyrin-based covalent organic framework (COF-366) coated with N-acetyl-galactosamine (GalNAc) and rhodamine B (RhB), and loaded with the first-line agent, Sorafenib (Sor).  The nanoplatform is targeted towards ASGPR-overexpressed HCC cells and liver tissues by  GalNAc  and observed by real-time imaging of RhB in vitro and in vivo. The nanoplatform  Sor@GR-COF-366 exerts an enhanced synergistic tumor suppression effect  in a subcutaneous HCC mouse model with a  tumor inhibition rate (TGI) of 97% while  significantly prolonging survival at very low toxicity. The potent synergistic therapeutic outcome is confirmed in an  orthotopic  mouse model of HCC with the TGI of 98% with a  minimally invasive interventional PDT (IPDT). Sor@GR-COF-366 is a promising candidate to be combined with chemo-IPDT for the treatment of HCC.

Keywords: Covalent-organic frameworks, chemotherapy, interventional photodynamic therapy, bimodal therapy, hepatocellular carcinoma