Evaluation of Triazole-Chelated Lanthanides as Chemically Stabile Bioimaging Agents

Europium (Eu), dysprosium (Dy), samarium (Sm), and terbium (Tb) complexes were prepared using the neutral tridentate chelator 2,6-bis(1-benzyl-1,2,3-triazol-4-yl)pyridine and one equivalent of each lanthanide salt. The physicochemical, aerodynamic, and in vitro cellular properties of each lanthanide...

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Veröffentlicht in:Journal of pharmaceutical sciences 2013-08, Vol.102 (8), p.2589-2598
Hauptverfasser: Indapurkar, Amruta, Henriksen, Brian, Tolman, Justin, Fletcher, James
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Henriksen, Brian
Tolman, Justin
Fletcher, James
description Europium (Eu), dysprosium (Dy), samarium (Sm), and terbium (Tb) complexes were prepared using the neutral tridentate chelator 2,6-bis(1-benzyl-1,2,3-triazol-4-yl)pyridine and one equivalent of each lanthanide salt. The physicochemical, aerodynamic, and in vitro cellular properties of each lanthanide metal complex were studied to determine their viability as cell surface fluorescent probes. Each compound was characterized by electrospray ionization mass spectroscopy (ESI-MS), ultraperformance liquid chromatography (UPLC), differential scanning calorimetry (DSC), and thermogravimetic analysis (TGA). Upon excitation at 320nm each complex displayed characteristic lanthanide-based fluorescence emission in the visible wavelength range with stokes shifts greater than 200nm. Each complex was found to be chemically stable when exposed to pH range of 1–11 for 72h and resistant to photobleaching. To simulate pulmonary administration of these fluorophores, the aerodynamic properties of the Eu and Tb complexes were determined using a next generation impactor (NGI). This measurement confirmed that the complexes retain their fluorescence emission properties after nebulization. Cellular cytotoxicity was determined on A-549 lung cancer cell line using methylthiazol tetrazolium (MTT) cytotoxicity assay at 24, 48, and 72h postexposure to the complexes. The complexes showed a dose and time-dependent effect on the percent viability of the cells. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 102:2589-2598, 2013
doi_str_mv 10.1002/jps.23616
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Cellular cytotoxicity was determined on A-549 lung cancer cell line using methylthiazol tetrazolium (MTT) cytotoxicity assay at 24, 48, and 72h postexposure to the complexes. 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subjects Aerodynamic properties
Calorimetry
cell culture
Cell Line, Tumor
Cell surface
Cell Survival - drug effects
Chelating Agents - chemistry
Chelating Agents - toxicity
chelation
Chemical compounds
Coordination Complexes - chemistry
Coordination Complexes - toxicity
Coordination compounds
Cytotoxicity
Differential scanning calorimetry
Dysprosium
Emissions
Europium
Fluorescence
fluorescence spectroscopy
Fluorescent Dyes - chemistry
Fluorescent Dyes - toxicity
Fluorescent indicators
fluorescent probes
Fluorophores
Humans
Ionization
Lanthanides
Lanthanoid Series Elements - chemistry
Lanthanoid Series Elements - toxicity
Liquid chromatography
Lung cancer
Mass spectroscopy
Medical imaging
Photobleaching
Samarium
Solubility
Terbium
thermal analysis
Thermogravimetric analysis
Toxicity
Triazoles - chemistry
Triazoles - toxicity
title Evaluation of Triazole-Chelated Lanthanides as Chemically Stabile Bioimaging Agents
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