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.
Bibliographical noteFunding Information:
This work was supported by the National Research Foundation of Korea (NRF) Grant, funded by the Korean government ( MSIT ) ( NRF-2015R1D1A1A01060710 and 2018R1D1A1A09082999 ) and a faculty research grant from Yonsei University College of Medicine (Grant No. 6-2015-0156 ). This research was also supported by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (Grant No. HI15C1744 ).
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All Science Journal Classification (ASJC) codes
- Chemical Engineering(all)