title: Synthesis and cell-selective antitumor properties of amino acid conjugated tumor-associated carbohydrate antigen-coated gold nanoparticles.
abstract: 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.
authors.affiliation: Chemical Biology Laboratory, The Center for Cancer Research, National Cancer Institute at Frederick, Frederick, MD 21702, United States.
authors.forename: Souvik
authors.initials: S
authors.lastname: Biswas
authors.affiliation: Chemical Biology Laboratory, The Center for Cancer Research, National Cancer Institute at Frederick, Frederick, MD 21702, United States.
authors.forename: Scott H
authors.initials: SH
authors.lastname: Medina
authors.affiliation: Chemical Biology Laboratory, The Center for Cancer Research, National Cancer Institute at Frederick, Frederick, MD 21702, United States. Electronic address: barchij@mail.nih.gov.
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Barchi
mesh_terms: D015295:Antigens, Tumor-Associated, Carbohydrate / Q000737:chemistry*; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D060326:Chemistry Techniques, Synthetic; D006046:Gold / Q000737:chemistry*; D006801:Humans; D053768:Metal Nanoparticles / Q000737:chemistry*; D012694:Serine / Q000737:chemistry* / Q000494:pharmacology*; D013912:Threonine / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D015295:Antigens, Tumor-Associated, Carbohydrate; D000970:Antineoplastic Agents; D013912:Threonine; C016467:Thomsen-Friedenreich antigen; D012694:Serine; D006046:Gold
keywords: Cytotoxicity; Galectin-3; Gold nanoparticles; Thomsen Friedenreich; Tumor-associated carbohydrate antigens