TY - JOUR
T1 - Synthesis and cell-selective antitumor properties of amino acid conjugated tumor-associated carbohydrate antigen-coated gold nanoparticles
AU - Biswas, Souvik
AU - Medina, Scott H.
AU - Barchi, Joseph J.
N1 - Funding Information:
The authors would like to thank the Dr. Kunio Nagashima and Ulrich Baxa of the Electron Microscopy laboratory of Leidos Biomedical Inc. for help with the TEM data, Dr. Anu Puri and Mr. Kshitij Gupta for help with acquiring DLS and zeta potential data and Jared Orwenyo and Lai-Xi Wang of the University of Maryland, Baltimore for help with the carbohydrate analysis of our particles. Funding for this work was supplied by The Intramural Program of the National Cancer Institute, Frederick, MD of the National Institutes of Health.
PY - 2015/3/20
Y1 - 2015/3/20
N2 - The Thomsen Friedenreich antigen (TFag) disaccharide is a tumor-associated carbohydrate antigen (TACA) found primarily on carcinoma cells and rarely expressed in normal tissue. The TFag has been shown to interact with Galectin-3 (Gal-3), one in a family of β-galactoside binding proteins. Galectins have a variety of cellular functions, and Gal-3 has been shown to be the sole galectin with anti-apoptotic activity. We have previously prepared gold nanoparticles (AuNP) coated with the TFag in various presentations as potential anti-adhesive therapeutic tools or antitumor vaccine platforms. Here we describe the synthesis of TFag-glycoamino acid conjugates attached to gold nanoparticles through a combined alkane/PEG linker, where the TFag was attached to either a serine or threonine amino acid. Particles were fully characterized by a host of biophysical techniques, and along with a control particle carrying hydroxyl-terminated linker units, were evaluated in both Gal-3 positive and negative cell lines. We show that the particles bearing the saccharides selectively inhibited tumor cell growth of the Gal-3 positive cells significantly more than the Gal-3 negative cells. In addition, the threonine-attached TF particles were more potent than the serine-attached constructs. These results support the use of AuNP as antitumor therapeutic platforms, targeted against cell lines that express specific lectins that interact with TFag.
AB - The Thomsen Friedenreich antigen (TFag) disaccharide is a tumor-associated carbohydrate antigen (TACA) found primarily on carcinoma cells and rarely expressed in normal tissue. The TFag has been shown to interact with Galectin-3 (Gal-3), one in a family of β-galactoside binding proteins. Galectins have a variety of cellular functions, and Gal-3 has been shown to be the sole galectin with anti-apoptotic activity. We have previously prepared gold nanoparticles (AuNP) coated with the TFag in various presentations as potential anti-adhesive therapeutic tools or antitumor vaccine platforms. Here we describe the synthesis of TFag-glycoamino acid conjugates attached to gold nanoparticles through a combined alkane/PEG linker, where the TFag was attached to either a serine or threonine amino acid. Particles were fully characterized by a host of biophysical techniques, and along with a control particle carrying hydroxyl-terminated linker units, were evaluated in both Gal-3 positive and negative cell lines. We show that the particles bearing the saccharides selectively inhibited tumor cell growth of the Gal-3 positive cells significantly more than the Gal-3 negative cells. In addition, the threonine-attached TF particles were more potent than the serine-attached constructs. These results support the use of AuNP as antitumor therapeutic platforms, targeted against cell lines that express specific lectins that interact with TFag.
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U2 - 10.1016/j.carres.2014.11.002
DO - 10.1016/j.carres.2014.11.002
M3 - Article
C2 - 25556664
AN - SCOPUS:84924175356
SN - 0008-6215
VL - 405
SP - 93
EP - 101
JO - Carbohydrate Research
JF - Carbohydrate Research
ER -
