Targeted tumor CT imaging using folic acid-modified PEGylated dendrimer-entrapped gold nanoparticles

Chen Peng; Jinbao Qin; Benqing Zhou; Qian Chen; Mingwu Shen; Meifang Zhu; Xinwu Lu; Xiangyang Shi

doi:10.1039/C3PY00521F

Targeted tumor CT imaging using folic acid-modified PEGylated dendrimer-entrapped gold nanoparticles†

Chen Peng,‡^a Jinbao Qin,‡^b Benqing Zhou,^c Qian Chen,^a Mingwu Shen,^c Meifang Zhu,^a Xinwu Lu*^b and Xiangyang Shi*^acd

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* Corresponding authors

^a State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, College of Materials Science and Engineering, Donghua University, Shanghai 201620, People's Republic of China

^b Department of Vascular Surgery, Shanghai Ninth People's Hospital Affiliated to Shanghai Jiaotong University, School of Medicine, Shanghai 200011, People's Republic of China
E-mail: luxinwu@yahoo.com.cn

^c College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620, People's Republic of China
E-mail: xshi@dhu.edu.cn

^d CQM-Centro de Química da Madeira, Universidade da Madeira, Campus da Penteada, 9000-390 Funchal, Portugal

Abstract

The development of multifunctional nanoprobes with a targeting capability for efficient molecular imaging of tumors still remains a great challenge. Herein, we report the synthesis and characterization of folic acid (FA)-modified dendrimer-entrapped gold nanoparticles (Au DENPs) via a facile polyethylene glycol (PEG) linking strategy for in vivo targeted tumor computed tomography (CT) imaging applications. In this study, amine-terminated poly(amidoamine) dendrimers of generation 5 (G5.NH₂) sequentially modified by two types of PEG moieties (PEG monomethyl ether with one end of carboxyl group (mPEG-COOH), and FA-modified PEG with one end of carboxyl group (FA-PEG-COOH)) were used as templates to synthesize AuNPs within the dendrimer interiors, followed by acetylation of the remaining dendrimer terminal amines. The formed multifunctional Au DENPs were characterized via different techniques. Cell viability assay, flow cytometric analysis of the cell cycles, and hemolysis assay were used to assess the cytotoxicity and hemocompatibility of the particles. We show that the formed multifunctional Au DENPs are stable at different pH and temperature conditions and in different aqueous media, cytocompatible and hemocompatible in the given Au concentration range, and display much higher X-ray attenuation intensity than Omnipaque (an iodine-based CT contrast agent) under similar concentrations of the active element (Au or iodine). Moreover, the developed Au DENPs enable targeted CT imaging of the model cancer cells with high FA receptor expression in vitro and the corresponding xenografted tumor model in vivo. These findings suggest that the designed Au DENPs may be used as promising contrast agents for targeted CT imaging of tumors.

Polymer Chemistry

Targeted tumor CT imaging using folic acid-modified PEGylated dendrimer-entrapped gold nanoparticles†

Abstract

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Targeted tumor CT imaging using folic acid-modified PEGylated dendrimer-entrapped gold nanoparticles

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