In this study, the imaging methods for evaluating the kinetics of nanoparticles as drug delivery systems in tumor tissues were improved in BxPC3 tumor-bearing mice. First, Förster resonance energy transfer (FRET) live imaging was selected to quantitatively evaluate nanoparticle kinetics in the tumor tissue of mice. Briefly, and 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine iodide (as an acceptor)-and 1,1'-dioctadecyl-3,3,3',3'-tetramethylindodicarbocyanine, 4-chlorobenzenesulfonate salt (as a donor)-coloaded nanoparticles were administered intravenously to the mice, and imaging was performed using a fluorescence in vivo imager. The fluorescence intensities of images were acquired in the FRET, donor, and acceptor channels, and the nanoparticle kinetics in the tumor region was quantified by compensating for bleed-through. Second, in the cleared tumor tissue of mice, the difference in evaluation properties between the two- and three-dimensional visualization of the nanoparticles was examined. In brief, 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI)-loaded nanoparticles were intravenously administered to the mice after fluorescently labeled tomato lectin treatment to visualize tumor vessels. Excised tumor tissue was cleared and observed using laser-scanning confocal microscopy, and three-dimensional images were reconstructed. The three-dimensional minimum distances traveled by DiI from the tumor vessels were calculated using information about the two-dimensional distance and the slicing position using the Pythagoras theorem. These imaging techniques should facilitate the development of drug delivery systems for cancer.
Keywords: Anticancer drug delivery system; BxPC3 tumor-bearing mice; Deep tissue imaging; Near-infrared FRET imaging; Three-dimensional imaging.
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