Gold nanoparticle-loaded macrophages enhance radiotherapy via immune remodeling in oral cancer

Gold nanoparticles (GNPs) are promising radiosensitizers owing to their high atomic number, but their therapeutic efficacy is often limited by reticuloendothelial system (RES)-mediated clearance and poor tumor accumulation attributable to elevated interstitial fluid pressure. This study explored mac...

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Main Authors: Hui-Wen Chan, Pei-Wei Sheung, Stella Tzu-Ming Tsao, Chun-Yi Wu, Hui-Yen Chuang
Format: Article
Language:English
Published: Elsevier 2025-08-01
Series:Materials Today Bio
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Online Access:http://www.sciencedirect.com/science/article/pii/S259000642500599X
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author Hui-Wen Chan
Pei-Wei Sheung
Stella Tzu-Ming Tsao
Chun-Yi Wu
Hui-Yen Chuang
author_facet Hui-Wen Chan
Pei-Wei Sheung
Stella Tzu-Ming Tsao
Chun-Yi Wu
Hui-Yen Chuang
author_sort Hui-Wen Chan
collection DOAJ
description Gold nanoparticles (GNPs) are promising radiosensitizers owing to their high atomic number, but their therapeutic efficacy is often limited by reticuloendothelial system (RES)-mediated clearance and poor tumor accumulation attributable to elevated interstitial fluid pressure. This study explored macrophage-mediated GNP delivery to enhance radiotherapy (RT) efficacy in oral cancer by leveraging the tumor-homing ability, immune plasticity, hypoxia tropism, and RES evasiveness of macrophages. Murine oral cancer cells (MCTQ1) and macrophages (RAW 264.7) were used. GNPs were synthesized using the Turkevich method, which were then assessed for radiosensitization using cell viability and colony formation assays. GNPs were radiolabeled with Iodine-131 (131I) using the chloramine-T method, and uptake by RAW 264.7 cells was quantified at various time points to optimize the generation of GNP-loaded macrophages (GNP@Rs). MTCQ1 tumor-bearing mice were divided into control, RT, GNP, RAW, GNP + RT, RAW + RT, and GNP@R + RT groups. Tumor volumes were monitored after GNP or cell administration and/or RT (8 Gy). Flow cytometry was used to analyze the immune cell populations post-treatment. Transwell assays confirmed that GNP loading did not impair macrophage migration, and in vivo fluorescence imaging demonstrated strong tumor tropism of RAW 264.7 cells and GNP@Rs. GNP@Rs maintained their migration ability and exhibited robust tumor accumulation for up to 96 h. Notably, GNP@R + RT treatment significantly enhanced tumor suppression relative to RT alone and increased the infiltration of macrophages, activated dendritic cells, CD4+ and CD8+ T cells, and natural killer cells. Macrophage-mediated GNP delivery successfully improved RT outcomes in oral cancer by increasing radiosensitivity and modulating immune microenvironment.
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spelling doaj-art-7ee76ae9fe7e4d3a8f73b292f5c72d2d2025-08-20T03:32:18ZengElsevierMaterials Today Bio2590-00642025-08-013310202910.1016/j.mtbio.2025.102029Gold nanoparticle-loaded macrophages enhance radiotherapy via immune remodeling in oral cancerHui-Wen Chan0Pei-Wei Sheung1Stella Tzu-Ming Tsao2Chun-Yi Wu3Hui-Yen Chuang4Department of Biomedical Imaging and Radiological Sciences, National Yang Ming Chiao Tung University, Taipei, 112, TaiwanDivision of Radiation Oncology, Department of Radiology, Far Eastern Memorial Hospital, New Taipei City, 220, Taiwan; Faculty of Medicine, School of Medicine, National Yang Ming Chiao Tung, Taipei City, 112, TaiwanDepartment of Biomedical Imaging and Radiological Sciences, National Yang Ming Chiao Tung University, Taipei, 112, TaiwanDepartment of Biomedical Imaging and Radiological Sciences, National Yang Ming Chiao Tung University, Taipei, 112, TaiwanDepartment of Biomedical Imaging and Radiological Sciences, National Yang Ming Chiao Tung University, Taipei, 112, Taiwan; Corresponding author. Department of Biomedical Imaging and Radiological Sciences, National Yang Ming Chiao Tung University, No. 155, Sec. 2, Li-Nong St., Beitou Dist., Taipei, 112, Taiwan.Gold nanoparticles (GNPs) are promising radiosensitizers owing to their high atomic number, but their therapeutic efficacy is often limited by reticuloendothelial system (RES)-mediated clearance and poor tumor accumulation attributable to elevated interstitial fluid pressure. This study explored macrophage-mediated GNP delivery to enhance radiotherapy (RT) efficacy in oral cancer by leveraging the tumor-homing ability, immune plasticity, hypoxia tropism, and RES evasiveness of macrophages. Murine oral cancer cells (MCTQ1) and macrophages (RAW 264.7) were used. GNPs were synthesized using the Turkevich method, which were then assessed for radiosensitization using cell viability and colony formation assays. GNPs were radiolabeled with Iodine-131 (131I) using the chloramine-T method, and uptake by RAW 264.7 cells was quantified at various time points to optimize the generation of GNP-loaded macrophages (GNP@Rs). MTCQ1 tumor-bearing mice were divided into control, RT, GNP, RAW, GNP + RT, RAW + RT, and GNP@R + RT groups. Tumor volumes were monitored after GNP or cell administration and/or RT (8 Gy). Flow cytometry was used to analyze the immune cell populations post-treatment. Transwell assays confirmed that GNP loading did not impair macrophage migration, and in vivo fluorescence imaging demonstrated strong tumor tropism of RAW 264.7 cells and GNP@Rs. GNP@Rs maintained their migration ability and exhibited robust tumor accumulation for up to 96 h. Notably, GNP@R + RT treatment significantly enhanced tumor suppression relative to RT alone and increased the infiltration of macrophages, activated dendritic cells, CD4+ and CD8+ T cells, and natural killer cells. Macrophage-mediated GNP delivery successfully improved RT outcomes in oral cancer by increasing radiosensitivity and modulating immune microenvironment.http://www.sciencedirect.com/science/article/pii/S259000642500599XMacrophage-based deliveryGold nanoparticlesRadiotherapyImmune responseRadiosensitization
spellingShingle Hui-Wen Chan
Pei-Wei Sheung
Stella Tzu-Ming Tsao
Chun-Yi Wu
Hui-Yen Chuang
Gold nanoparticle-loaded macrophages enhance radiotherapy via immune remodeling in oral cancer
Materials Today Bio
Macrophage-based delivery
Gold nanoparticles
Radiotherapy
Immune response
Radiosensitization
title Gold nanoparticle-loaded macrophages enhance radiotherapy via immune remodeling in oral cancer
title_full Gold nanoparticle-loaded macrophages enhance radiotherapy via immune remodeling in oral cancer
title_fullStr Gold nanoparticle-loaded macrophages enhance radiotherapy via immune remodeling in oral cancer
title_full_unstemmed Gold nanoparticle-loaded macrophages enhance radiotherapy via immune remodeling in oral cancer
title_short Gold nanoparticle-loaded macrophages enhance radiotherapy via immune remodeling in oral cancer
title_sort gold nanoparticle loaded macrophages enhance radiotherapy via immune remodeling in oral cancer
topic Macrophage-based delivery
Gold nanoparticles
Radiotherapy
Immune response
Radiosensitization
url http://www.sciencedirect.com/science/article/pii/S259000642500599X
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AT peiweisheung goldnanoparticleloadedmacrophagesenhanceradiotherapyviaimmuneremodelinginoralcancer
AT stellatzumingtsao goldnanoparticleloadedmacrophagesenhanceradiotherapyviaimmuneremodelinginoralcancer
AT chunyiwu goldnanoparticleloadedmacrophagesenhanceradiotherapyviaimmuneremodelinginoralcancer
AT huiyenchuang goldnanoparticleloadedmacrophagesenhanceradiotherapyviaimmuneremodelinginoralcancer