Enhancement of antitumor effect of radiotherapy via combination with Au@SiO2 nanoparticles targeted to tumor-associated macrophages

Abstract

Tumor-associated macrophages (TAMs) exhibit the M2 phenotype and serve as critical tumor-promoting immune cells in the tumor microenvironment. As TAMs are an important target, we examined the effect of gold nanoparticles (AuNPs) with radiotherapy (RT) on M2 TAMs in tumors. We synthesized CD163 antibody-conjugated, silica-coated AuNPs (CD163-GNPs) that were specifically recognized by M2 TAMs. Bone marrow-derived macrophages and Raw 264.7 macrophages were polarized into M1 and M2 phenotypes. The effect of CD163-GNPs combined with RT was evaluated in a CT26 syngeneic mouse model (BALB/c mice). Immunostaining, flow cytometry, microscopic analyses, enzyme-linked immunosorbent assay, quantitative real-time polymerase chain reaction (qRT-PCR), and tumor growth delay assay were performed following irradiation combined with CD163-GNP treatment. We observed selective phagocytosis of CD163-GNPs by Raw 264.7 macrophages following M1/M2 polarization. Immunostaining analyses revealed higher numbers of CD163-GNPs taken up by M2 macrophages than M0 or M1 type. CD163-GNPs combined with RT significantly reduced tumor growth in the CT26 syngeneic mouse model. Macrophages subjected to the combination treatment showed increased expression of M1 markers. The depletion of M2 TAMs in tumors upon combination treatment with CD163-GNPs enhances the efficiency of RT.