Introduction: One of the main causes of death worldwide is cancer. The capacity of theranostic prodrugs to provide simultaneous diagnosis and therapy has drawn more and more attention in recent years. Here, we present the development of a novel theranostic molecule, called GF, based on the fluorescent dye 5(6)-carboxyfluorescein and the nucleoside anticancer drug gemcitabine.
Material and Methods: By using confocal microscopy to assess the synthesized GF's mode of cell uptake and cellular localization, a clathrin-mediated endocytosis was also revealed. Furthermore, three distinct human cancer lines—A549 (lung cancer), U87 and T98 (glioblastoma) were used to investigate the in vitro cytotoxicity and its pharmacokinetic profile in mice. Lastly, the effectiveness of the treatment in vivo was assessed using zebrafish and xenografted mice.
Results: GF has the ability to effectively enter tumor cells and locate in the lysosomes, which are the site of drug release and anticancer action. In mice, GF demonstrated improved pharmacokinetics as compared to gemcitabine. Higher concentrations of GF had notable anti-proliferative effects; yet, at all tested concentrations in all cell lines, GF was shown to be less cytotoxic than gemcitabine.
Conclusion: These findings suggest that GF, as a prodrug, can be a highly effective cytotoxic agent against glioblastoma. Additionally, as a potential gemcitabine prodrug, GF demonstrated less cytotoxic action than gemcitabine.
