Enzyme-instructed assembly of a cholesterol conjugate promotes pro-inflammatory macrophages and induces apoptosis of cancer cells
The combination of immunotherapy and chemotherapy has shown great potential to treat solid tumors. Although various combination therapy regimens have been demonstrated effective, their implementation in practice always needs separate drugs or modalities, which in turn requires specific and complicated operation procedures. Here, we describe the use of enzyme-instructed self-assembly (EISA) of a phosphotyrosine-cholesterol (PTC) conjugate to combine immune microenvironment modulation and chemotherapy. The enzymatic dephosphorylation of PTC results in the assembly of its derivative inside and outside cells, which leads to a repolarization of macrophage phenotype and direct death of cancer cells. The generation of reactive oxygen species and actin disturbance induced by the assemblies has been verified relative to the macrophage repolarization. We also demonstrate its dual repolarization and inhibition effects in vivo by using an ovarian cancer bearing immunocompetent murine model. EISA of cholesterol conjugates provides an effective yet simple approach for the combination of tumor microenvironment immunomodulation and chemotherapy.