The localization and behavior of fluorescently tagged magnetic nanoparticles in biological systems.

摘要

A novel combination cancer therapy platform incorporating chemotherapy and hyperthermia is proposed. Magnetic nanoparticles are included as a way to achieve the hyperthermia treatment, as well as for use as a platform for targeting, imaging, or other therapeutic moieties. Cobalt ferrite (CoFe 2O4) magnetic nanoparticles (MNPs) were synthesized and tagged with the fluorescent dye rhodamine for tracking in biological systems. The MNP solutions were characterized to determine average diameters of the nanoparticles. Results indicate that sample age, solvent, and concentration can affect the diameters of MNP agglomerates as measured by dynamic light scattering. Older and more concentrated samples, which also tend to be less stable, showed larger MNP sizes than newer and less concentrated samples. Rhodamine-tagged MNPs showed smaller diameters than untagged MNPs at the same concentrations. For MNP in HeLa cell localization studies, the rhodamine-tagged MNPs showed uptake and localization in the cytoplasm of the cells. Partition coefficients, or the ratios of MNP concentrations inside the cells to the extracellular concentration, were shown to increase during the first 6 h of incubation time, with values reaching as high as 3.805, indicating favorable uptake of the MNPs. After 24 h, a smaller ratio of internalized MNPs was seen due to cytotoxic properties of the high concentration of MNPs used in those experiments. Toxicity studies showed that at concentrations below approximately 0.025 mg/mL, both rhodamine-tagged and untagged CoFe2O4 MNPs have little effect on cell viability. MNP localization and toxicity studies were also carried out on a model organism, C. elegans worms, with an indication that rhodamine-tagged CoFe2O4 MNPs were non-toxic to worms over a period of 12 days. Localization of the MNPs within the worms was inconclusive due to indistinguishable autofluorescence of the C. elegans and the rhodamine fluorescence of tagged MNPs. Further work is needed to characterize the CoFe2O4 MNPs for use in the cancer treatment platform.