title: PEGylated polyethylenimine-entrapped gold nanoparticles modified with folic acid for targeted tumor CT imaging.
abstract: Development of various cost-effective contrast agents for targeted tumor computed tomography (CT) imaging still remains a great challenge. Herein, we present a facile approach to forming folic acid (FA)-targeted multifunctional gold nanoparticles (AuNPs) using cost-effective branched polyethylenimine (PEI) modified with polyethylene glycol (PEG) as a template for tumor CT imaging applications. In this work, PEI sequentially modified with PEG monomethyl ether, FA-linked PEG, and fluorescein isothiocyanate was used as a template to synthesize AuNPs, followed by transformation of the remaining PEI surface amines to acetamides. The formed FA-targeted PEI-entrapped AuNPs (FA-Au PENPs) were fully characterized. We show that the formed FA-Au PENPs with an Au core size of 2.1 nm are water soluble, colloidally stable, and non-cytotoxic in a given concentration range. Flow cytometry and confocal microscopy data reveal that the FA-Au PENPs are able to target cancer cells overexpressing FA receptors (FAR). Importantly, the developed FA-Au PENPs can be used as a nanoprobe for targeted CT imaging of FAR-expressing cancer cells in vitro and the xenografted tumor model in vivo. With the demonstrated biocompatibility by organ biodistribution and histological studies, the designed FA-Au PENPs may hold great promise to be used as a nanoprobe for CT imaging of different FAR-overexpressing tumors.
authors.affiliation: College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620, People's Republic of China.
authors.forename: Benqing
authors.initials: B
authors.lastname: Zhou
authors.affiliation: Department of Radiology, Shanghai General Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200080, People's Republic of China.
authors.forename: Jia
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Radiology, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai 200072, People's Republic of China.
authors.forename: Chen
authors.initials: C
authors.lastname: Peng
authors.affiliation: College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620, People's Republic of China.
authors.forename: Jianzhi
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Experiment Center, Shanghai General Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200080, People's Republic of China.
authors.forename: Yueqin
authors.initials: Y
authors.lastname: Tang
authors.affiliation: College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620, People's Republic of China.
authors.forename: Xiaoyue
authors.initials: X
authors.lastname: Zhu
authors.affiliation: College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620, People's Republic of China.
authors.forename: Mingwu
authors.initials: M
authors.lastname: Shen
authors.affiliation: Department of Radiology, Shanghai General Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200080, People's Republic of China. Electronic address: guixinagzhang@sina.com.
authors.forename: Guixiang
authors.initials: G
authors.lastname: Zhang
authors.affiliation: College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620, People's Republic of China; Department of Radiology, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai 200072, People's Republic of China; CQM-Centro de Química da Madeira, Universidade da Madeira, Campus da Penteada, 9000-390 Funchal, Portugal. Electronic address: xshi@dhu.edu.cn.
authors.forename: Xiangyang
authors.initials: X
authors.lastname: Shi
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003102:Colloids / Q000737:chemistry; D003287:Contrast Media / Q000737:chemistry; D058973:Folate Receptors, GPI-Anchored / Q000037:antagonists & inhibitors; D005492:Folic Acid / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D006046:Gold / Q000737:chemistry*; D006801:Humans; D053768:Metal Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D018613:Microscopy, Confocal; D046529:Microscopy, Electron, Transmission; D009369:Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism; D011092:Polyethylene Glycols / Q000737:chemistry*; D011094:Polyethyleneimine / Q000737:chemistry*; D012995:Solubility; D014057:Tomography, X-Ray Computed / Q000379:methods*; D014183:Transplantation, Heterologous
chemical_list: D003102:Colloids; D003287:Contrast Media; D058973:Folate Receptors, GPI-Anchored; D011092:Polyethylene Glycols; D006046:Gold; D011094:Polyethyleneimine; D005492:Folic Acid
keywords: CT imaging; Folic acid; Gold nanoparticles; Polyethyleneimine; Tumors