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Targeted Tumor Computed Tomography Imaging Using Low‐Generation Dendrimer‐Stabilized Gold Nanoparticles
Author(s) -
Liu Hui,
Xu Yanhong,
Wen Shihui,
Chen Qian,
Zheng Linfeng,
Shen Mingwu,
Zhao Jinglong,
Zhang Guixiang,
Shi Xiangyang
Publication year - 2013
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201204612
Subject(s) - dendrimer , in vivo , materials science , in vitro , biocompatibility , colloidal gold , imaging agent , preclinical imaging , mtt assay , nanomedicine , nanoparticle , biophysics , folate receptor , cancer cell , chemistry , biomedical engineering , nanotechnology , cancer , polymer chemistry , biochemistry , medicine , microbiology and biotechnology , metallurgy , biology
Abstract We report a facile approach to fabricating low‐generation poly(amidoamine) (PAMAM) dendrimer‐stabilized gold nanoparticles (Au DSNPs) functionalized with folic acid (FA) for in vitro and in vivo targeted computed tomography (CT) imaging of cancer cells. In this study, amine‐terminated generation 2 PAMAM dendrimers were employed as stabilizers to form Au DSNPs without additional reducing agents. The formed Au DSNPs with an Au core size of 5.5 nm were covalently modified with the targeting ligand FA, followed by acetylation of the remaining dendrimer terminal amines to endow the particles with targeting specificity and improved biocompatibility. Our characterization data show that the formed FA‐modified Au DSNPs are stable at different pH values (5—8) and temperatures (4–50 °C), as well as in different aqueous media. MTT assay data along with cell morphology observations reveal that the FA‐modified Au DSNPs are noncytotoxic in the particle concentration range of 0–3000 n M . X‐ray attenuation coefficient measurements show that the CT value of FA‐modified Au DSNPs is much higher than that of Omnipaque (a clinically used CT contrast agent) at the same concentration of the radiodense elements (Au or iodine). Importantly, the FA‐modified Au DSNPs are able to specifically target a model cancer cell line (KB cells, a human epithelial carcinoma cell line) over‐expressing FA receptors and they enable targeted CT imaging of the cancer cells in vitro and the xenografted tumor model in vivo after intravenous administration of the particles. With the simple synthesis approach, easy modification, good cytocompatibility, and high X‐ray attenuation coefficient, the FA‐modified low‐generation Au DSNPs could be used as promising contrast agents for targeted CT imaging of different tumors over‐expressing FA receptors.