首页|Cetuximab-anchored gold nanorod mediated photothermal ablation of breast cancer cell in spheroid model embedded with tumor associated macrophage
Cetuximab-anchored gold nanorod mediated photothermal ablation of breast cancer cell in spheroid model embedded with tumor associated macrophage
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NSTL
Elsevier
Triple-negative breast cancer constitutes 15 - 20% of all breast cancer and is considered one of the most aggressive forms of breast cancer. Clinical studies have suggested that the high numbers of infiltrating tumor-associated macrophage (TAM) act as a critical contributor behind the aggression of TNBC. Therefore, this study was focused on the preparation of a TNBC spheroid model with M2-like macro-phages (M2-M) since it closely simulated the tumor microenvironment observed in clinical TNBC tumors. High EGFR expression in TNBC highlights the importance of cetuximab (Cmab)-assisted cellular internal-ization into the EGFR overexpressing TNBC cell line. The Cmab-anchored gold nanorod (GNR)-mediated photothermal approach was successfully developed to treat the TAM-infiltrated TNBC spheroid model. MDA-MB-231 spheroids with a diameter of 260 +/- 10 lm were successfully prepared. An increase in the IC50 of doxorubicin in MDA-MB-231 spheroids with M2-M compared to the without M2-M group sug-gested that TAM-mediated development of resistance. The in vitro cytotoxicity assay demonstrated that there was elevated apoptosis expression (PARP and caspase-9), cell cycle arrest (G2/M phase), and cyto-toxic effects following treatment with Cmab-GNR plus NIR irradiation. Moreover, there was no significant difference between the cytotoxic effect of Cmab-GNR plus NIR with M2-M and without M2-M group. Thus, our study highlighted that Cmab-GNR with NIR were able to overcome TAM-acquired resistance in the tumor model, which might be due to the polarization of the protumoral phenotype to the antitu-moral phenotype. (C) 2021 The Korean Society of Industrial and Engineering Chemistry. Published by Elsevier B.V. All rights reserved.