Folate-modified gold nanoclusters as near-infrared fluorescent probes for tumor imaging and therapy |
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Authors: | Haiyan Chen Shulan Li Bowen Li Xueyan Ren Shengnan Li Didel M Mahounga Sisi Cui Yueqing Gu Samuel Achilefu |
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Affiliation: | Department of Biomedical Engineering, School of Life Science and Technology, State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tongjia Lane, Gulou District, Nanjing 210009, China. guyueqing@hotmail.com. |
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Abstract: | Ultra-small gold nanoclusters (Au NCs) are highly promising materials for tumor imaging and therapy because of their low toxicity, intrinsic fluorescence, and the availability of multifunctional groups for covalent linkage of diverse bioactive molecules. Au NCs stabilized by bovine serum albumin (BSA) were prepared via an improved "green" synthetic routine. To ameliorate the selective affinity of Au NCs for high folate receptor (FR) expressing tumors, folic acid (FA) was immobilized on the surface of Au NCs. Subsequently, a near-infrared (NIR) fluorescent dye MPA was conjugated with Au-FA NCs for in vitro and in vivo fluorescence imaging. Similarly, Doxorubicin (DOX), a widely used clinical anticancer drug, was also conjugated to the folate-modified Au NCs to form a prodrug (Au-FA-DOX). Cellular and in vivo acute toxicity studies demonstrated the low toxicity of the Au-FA-MPA to normal cells and tissues. Additionally, in vitro and in vivo study of the dynamic behavior and targeting ability of Au-FA-MPA to different tumors validated the high selective affinity of Au-FA-MPA to FR positive tumors. With regard to the Au-FA-DOX, high anti-tumor activity was displayed by this pro-drug due to the FR mediated uptake. Herein, all of the results supported the potential of using ligand-modified Au NCs for tumor imaging and targeted therapy. |
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