International Journal of Nanomedicine (Oct 2018)
Biomimetic quantum dot-labeled B16F10 murine melanoma cells as a tool to monitor early steps of lung metastasis by in vivo imaging
Abstract
Víctor Manuel Díaz-García,1–4 Simón Guerrero,1,2,5 Natalia Díaz-Valdivia,1,2 Lorena Lobos-González,2,6,7 Marcelo Kogan,2,5 José Manuel Pérez-Donoso,3 Andrew FG Quest1,21Cellular Communication Laboratory, Center for Studies on Exercise, Metabolism and Cancer (CEMC), Faculty of Medicine, Universidad de Chile, Santiago, Chile; 2Advanced Center for Chronic Diseases (ACCDiS), Faculty of Medicine, Universidad de Chile, Santiago, Chile; 3BioNanotechnology and Microbiology Laboratory, Center for Bioinformatics and Integrative Biology (CBIB), Faculty of life Sciences, Universidad Andres Bello, Santiago, Chile; 4Facultad de Ingeniería y Tecnología, Universidad San Sebastián, Concepción 4080871, Chile; 5Department of Pharmacological and Toxicological Chemistry, Faculty of Chemical and Pharmaceutical Sciences, Universidad de Chile, Santiago, Chile; 6Fundación Ciencia y Vida, Santiago, Chile; 7Centro de Medicina Regenerativa, Facultad de Medicina, Clínica Alemana, Universidad del Desarrollo , Santiago, ChileBackground: Numerous studies have proposed the use of fluorescent semiconductor nanoparticles or quantum dots (QDs) as novel tools to label cells and tumors. However, QD applications are limited by their toxicity in biological systems and little is known about whether QDs affect the capacity of cancer cells to metastasize. Previously, we described the “biomimetic” synthesis of CdTe-QDs (QDs-glutathione [GSH]) with increased biocompatibility and the potential utility in labeling cells.Purpose: In order to determine the feasibility of using QDs-GSH as a tool for tracking tumor cells during early metastasis, we characterized here for the first time, the in vitro and in vivo effects of the incorporation of green or red biomimetic QDs-GSH into B16F10 cells, a syngeneic mouse melanoma line for metastasis assays in C57BL/6 mice.Methods: B16F10 cells were labeled with green or red biomimetic QDs-GSH in the presence or absence of n-acetylcysteine. Then, migration, invasion and proliferation of labeled B16F10 were evaluated in vitro. Finally, the B16F10 cells labeled with red QDs-GSH were used to monitor in vivo lung metastasis at early time points (5 minutes to 24 hours) or after 21 days in C57BL/6 mice.Results: We developed a methodology that allows obtaining QDs-GSH-labeled B16F10 cells (nearly 100% viable labeled cells), which remained viable for at least 5 days and migrated similarly to control cells. However, proliferation, invasion, and the capacity to form metastatic nodules in the lungs were severely attenuated. Fluorescence imaging revealed that distribution/accumulation of QDs-GSH-labeled B16F10 cells could be tracked following injection into C57BL/6 mice (syngeneic preclinical metastasis model) and that these cells preferentially accumulated in the perialveolar area in lungs as early as 5 minutes post-injection.Conclusion: The methodology described here represents a useful alternative for monitoring initial events during tumor cell metastasis.Keywords: cell tracking, biomimetic, invasion, proliferation, migration, cancer
