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

Authors
 Mi Sun Kim  ;  Jae Sang Lee  ;  Jung Eun Kim  ;  Jae-Won Kim  ;  Seoyeon Bok  ;  Ki Chang Keum  ;  Won-Gun Koh  ;  Woong Sub Koom 
Citation
 JOURNAL OF INDUSTRIAL AND ENGINEERING CHEMISTRY, Vol.84 : 349-357, 2020-04 
Journal Title
 JOURNAL OF INDUSTRIAL AND ENGINEERING CHEMISTRY 
ISSN
 1226-086X 
Issue Date
2020-04
Keywords
Tumor-associated macrophage (TAM) ; M2 TAM-targeting gold nanoparticles ; Radiotherapy combined with gold nanoparticles ; Tumor microenvironment
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.
Full Text
https://www.sciencedirect.com/science/article/pii/S1226086X20300265
DOI
10.1016/j.jiec.2020.01.017
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Radiation Oncology (방사선종양학교실) > 1. Journal Papers
Yonsei Authors
Keum, Ki Chang(금기창) ORCID logo https://orcid.org/0000-0003-4123-7998
Koom, Woong Sub(금웅섭) ORCID logo https://orcid.org/0000-0002-9435-7750
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/176160
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