21 February 2013 Covalent IR820-PEG diamine conjugates: characterization and in vivo biodistribution
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Abstract
Introduction: IR820 is a near-infrared probe with potential applications in optical imaging and hyperthermia. Its chlorosubstituted cyclohexene makes it amenable to forming conjugates as multifunctional probes. We prepared a novel covalent IR820/PEG-diamine (IRPDcov) nanoconjugate. Methods: IRPDcov was prepared using IR820 and 6kDa PEG-diamine, characterized by SEM, H-NMR, spectrophotometry, and spectrofluorometry; and studied in vitro and in vivo. Mice (n=36) were used to explore the biodistribution of IRPDcov compared to IR820 and indocyanine green (ICG) after i.v. injection of a 0.24 mg/kg dose of dye, with plasma samples collected at 15-30-60 minutes and 24 hours. The plasma concentrations were fit to a biexponential curve following a two compartment model. Organ samples were collected after 24 hours. Results and Discussion: IRPDcov retained the ability to fluoresce for in vivo optical imaging and also to generate heat, and was significantly more stable than IR820 in aqueous solution over a period of 72 hours. IRPDcov and IR820 demonstrated significantly longer (p<0.05) plasma half-lives, elimination half-lives, and area-under-the-curve values compared to ICG. This could pose an advantage in therapeutic probe applications such as hyperthermia or drug delivery. Both IR820 and IRPDcov showed a very strong signal in the liver and lower-intensity signal in the kidneys 24 hours after injection, whereas the predominant signal for ICG was weak and located in the intestines, demonstrating a much more rapid GI elimination. IR820 showed signal in the lungs, which was not present in IRPDcov subjects indicating that IRPDcov may have been able to escape detection by alveolar macrophages.
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Alicia Fernandez-Fernandez, Alicia Fernandez-Fernandez, Romila Manchanda, Romila Manchanda, Denny A. Carvajal, Denny A. Carvajal, Tingjun Lei, Tingjun Lei, Anthony J. McGoron, Anthony J. McGoron, } "Covalent IR820-PEG diamine conjugates: characterization and in vivo biodistribution", Proc. SPIE 8596, Reporters, Markers, Dyes, Nanoparticles, and Molecular Probes for Biomedical Applications V, 859605 (21 February 2013); doi: 10.1117/12.2004869; https://doi.org/10.1117/12.2004869
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