NMR as Evaluation Strategy for Cellular Uptake of Nanoparticles

Abstract

Advanced nanostructured materials, such as gold nanoparticles, magnetic nanoparticles, and multifunctional materials, are nowadays used in many state-of-the-art biomedical application. However, although the engineering in this field is very advanced, there remain some fundamental problems involving the interaction mechanisms between nanostructures and cells or tissues. Here we show the potential of (1)H NMR in the investigation of the uptake of two different kinds of nanostructures, that is, maghemite and gold nanoparticles, and of a chemotherapy drug (Temozolomide) in glioblastoma tumor cells. The proposed experimental protocol provides a new way to investigate the general problem of cellular uptake for a variety of biocompatible nanostructures and drugs.

Rhamnose‐coated superparamagnetic iron‐oxide nanoparticles: an evaluation of their in vitro cytotoxicity, genotoxicity and carcinogenicity

“…According to the presented results, it is possible to state the uptake of rhamnose-coated nanoparticles by different kinds of tumor cells confirming previously data published (Orlando et al, 2014) and to validate the choice of rhamnose as a biocompatible coating.…”

“…2c in which, at the highest concentrations (50 and 100 μgFe ml -1 ), the total iron content inside the cells was lower than the concentration of iron-oxide nanoparticles incubated at the beginning of the experiment. It means a higher presence of IONPs in the cell medium and a lower phagocytic activity by carbohydrate-binding proteins as hypothesized in the study by Orlando et al (2014) The internalization of IONPs higher in glioblastoma cells than human urinary bladder carcinoma cells confirm the high invasive ability of this astrocytic tumor. Furthermore, the lower internalization by the ECV304 cell line widely, used in in vitro permeation studies (Braun et al, 2000;Barar et al, 2010;Wang et al, 2011), could suggest an important role of the biological barrier in obstructing the passage of rhamnose-coated IONPs to the brain tumor mass.…”

“…S1, respectively, it is possible to give a qualitative trend of nanoparticles internalization in the ECV304 cell line but this technique does not allow the measurement of the effective intracellular concentration of nanoparticles in each condition or in each cell. This limitation was already observed in a previous publication (Orlando et al, 2014), in which was reported a series of Prussian blue images about the interaction between glioblastoma cells lines (T98G and U251) and rhamnose-coated iron-oxide nanoparticles. Following the real evidence of an internalization process of rhamnose-coated iron-oxide nanoparticles by the three lines tested ( Fig.…”

“…Following the real evidence of an internalization process of rhamnose-coated iron-oxide nanoparticles by the three lines tested ( Fig. S1; Orlando et al, 2014) the intracellular iron content assay was carried out. This kind of experiment permits to associate the iron concentrations to specific spectrophotometric values read at a wavelength of 490 nm and successively to quantify these values using a calibration curve.…”

NMR relaxation induced by iron oxide particles: testing theoretical models

“…The size of the particles is an important parameter for biomedical applications: these contrast agents often cluster in cellular culture and in vivo, which leads to the formation of larger 'magnetic entities' [19][20][21][22][23]. Therefore, a relaxation model valid in aqueous solutions with well dispersed particles fails to be a satisfactory approach to predict the behavior of the larger clusters often observed in cells [12,[21][22][23]. The same is true for the diffusion properties of water protons: diffusion can be up to three times slower in cells [24] than in aqueous solutions, which could also change the relaxation regime.…”