Biomimetic quantum dot-labeled B16F10 murine melanoma cells as a tool to monitor early steps of lung metastasis by in vivo imaging

Abstract

BackgroundNumerous 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.PurposeIn 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.MethodsB16F10 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.ResultsWe 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.ConclusionThe methodology described here represents a useful alternative for monitoring initial events during tumor cell metastasis.

AT2 Receptor Mediated Activation of the Tyrosine Phosphatase PTP1B Blocks Caveolin-1 Enhanced Migration, Invasion and Metastasis of Cancer Cells

“…CAV1 has been suggested to promote melanoma metastasis by enhancing extravasation [40]. Consistent with the latter findings, we have shown that CAV1 promotes transendothelial migration in vitro [29] and very early events in lung colonization by melanoma cells [41]. Indeed, we observed here that CAV1-enhanced transendothelial migration of melanoma cells is blocked by CGP42112 treatment.…”

Anti-Proliferative, Pro-Apoptotic, Anti-Migrative and Tumor-Inhibitory Effects and Pleiotropic Mechanism of Theaflavin on B16F10 Melanoma Cells

“…The B16F10 cells we applied is the most widely used cell type of melanoma with an elevated metastatic potential that acts as a well-established preclinical model for evaluating the anti-melanoma efficacy of therapeutics. 24 This model has important benefits over xeno-transplantation or genetically modified models since mice possess a normal immune system that opens a useful platform for new therapies and adequate host response. 25 Moreover, B16F10 tumor growth drives pro-inflammatory response and muscle loss that are associated with impaired skeletal muscle strength and decreased locomotion and exploratory activity in B16F10 tumor-bearing mice, promoting cancer cachexia.…”

Bacterial phototoxicity of biomimetic CdTe‐GSH quantum dots

“…Also, the fluorescence sensibility of QDs is two to three times higher than most organic fluorophores commonly used in live imaging (Díaz‐García et al . 2018), a situation that has favoured their use as a fluorescent tool for in vivo assays. The surfaces of QDs can be modified, improving their active targeting, or the addition of diagnostic or therapeutic groups (Akerman et al .…”

“…Our red and green biomimetic fluorescent NPs were used to track metastatic cells in mice with no effect on animal viability (Díaz‐García et al . 2018). QDs‐labelled B16F10 cells remained viable for at least 5 days and migrated similarly to control cells.…”

“…Fluorescence imaging showed that QDs‐labelled B16F10 cells can be tracked following injection into C57BL/6 mice, and these cells preferentially accumulated in the perialveolar area of the lungs (Díaz‐García et al . 2018). Despite all these antecedents regarding the effect of biomimetic CdTe‐GSH QDs in different biological systems, no studies to determine their phototoxic effect have been performed to date.…”