WO3-x@Ferrocene-Folic Acid Composites Induce Cancer Cell Death and Activate Immunity via PTT/CDT

Abstract

At present, tumor immune escape is a major problem in the treatment of tumors. The complex network of tumor microenvironments significantly impairs the efficacy of immunotherapy. This paper reports the preparation and immunoantitumor activity of a novel multifunctional defect tungsten trioxide@ferrocene-folic acid composite (WO_3-x@Fe-FA) with a high Fenton reaction rate. Ferrocene is modified on the surface of defective trioxide by the covalent coupling method for the first time, and the reaction rate of Fenton is increased by 10 times. WO_3-x@Fe-FA induces immunogenic cell death (ICD) through the powerful synergistic anti-tumor effect of PTT/CDT and decomposes H₂O₂ to produce oxygen through the Fenton reaction, thus down-regulating the expression of immune checkpoint PD-L1 induced by tumor hypoxia. In vitro and in vivo experiments proved that WO_3-x@Fe-FA reverses the immunosuppressive tumor microenvironment, transforms the immunosuppressive "cold tumor" into the immune "hot tumor", and activates the immune activity of the system. In vitro and in vivo experiments show that WO_3-x@Fe-FA has excellent immunoantitumor activity, and it is expected to be a candidate drug for immunoantitumor therapy.

Keywords: defect tungsten oxides; ferrocene; immunogenic cell death (ICD); self‐oxygenation; tumor microenvironment.