期刊
INTERNATIONAL JOURNAL OF RADIATION BIOLOGY
卷 92, 期 11, 页码 716-723出版社
TAYLOR & FRANCIS LTD
DOI: 10.3109/09553002.2016.1145360
关键词
Gold nanoparticles; Auger electron emitters; EGF; Indium-111; targeted radiotherapy
资金
- Cancer Research UK [11564, 16466] Funding Source: researchfish
Purpose Radiolabeled antibodies and peptides hold promise for molecular radiotherapy but are often limited by a low payload resulting in inadequate delivery of radioactivity to tumour tissue and, therefore, modest therapeutic effect. We developed a facile synthetic method of radiolabeling indium-111 (In-111) to epidermal growth factor (EGF)-gold nanoparticles (In-111-EGF-Au NP) with a high payload.Materials and methods EGF-Au NP were prepared via an interaction between gold and the disulphide bonds of EGF and radiolabeled using (InCl3)-In-111. Targeting efficiency was investigated by quantitating internalized radioactivity and by confocal imaging following exposure of MDA-MB-468 (1.3 x 10(6) EGFR/cell) and MCF-7 (10(4) EGFR/cell) cells to Cy3-EGF-Au NP. Cytotoxicity was evaluated in clonogenic assays.Results The proportion of total administered radioactivity that was internalized by MDA-MB-468 and MCF-7 cells was 15% and 1.3%, respectively (mixing ratio of EGF:Au of 160). This differential uptake in the two cell lines was confirmed using confocal microscopy. In-111-EGF-Au NP were significantly more radiotoxic to MDA-MB-468 than MCF-7 cells with a surviving fraction of 17.1 4.4% versus 89.8 +/- 1.4% (p < 0.001) after exposure for 4h.Conclusions An In-111-labeled EGF-Au nanosystem was developed. It enabled targeted delivery of a high In-111 payload specifically to EGFR-positive cancer cells leading to radiotoxicity that can be exploited for molecularly targeted radiotherapy.
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