Quantification of the internalization patterns of superparamagnetic iron oxide nanoparticles with opposite charge

Abstract

Time-resolved quantitative colocalization analysis is a method based on confocal fluorescence microscopy allowing for a sophisticated characterization of nanomaterials with respect to their intracellular trafficking. This technique was applied to relate the internalization patterns of nanoparticles i.e. superparamagnetic iron oxide nanoparticles with distinct physicochemical characteristics with their uptake mechanism, rate and intracellular fate.The physicochemical characterization of the nanoparticles showed particles of approximately the same size and shape as well as similar magnetic properties, only differing in charge due to different surface coatings. Incubation of the cells with both nanoparticles resulted in strong differences in the internalization rate and in the intracellular localization depending on the charge. Quantitative and qualitative analysis of nanoparticles-organelle colocalization experiments revealed that positively charged particles were found to enter the cells faster using different endocytotic pathways than their negative counterparts. Nevertheless, both nanoparticles species were finally enriched inside lysosomal structures and their efficiency in agarose phantom relaxometry experiments was very similar.This quantitative analysis demonstrates that charge is a key factor influencing the nanoparticle-cell interactions, specially their intracellular accumulation. Despite differences in their physicochemical properties and intracellular distribution, the efficiencies of both nanoparticles as MRI agents were not significantly different.

Fluorescent graphene quantum dots as traceable, pH-sensitive drug delivery systems

“…13 Furthermore, if in vivo applications are envisaged, some tumors are characterized by a slightly more acidic environment than healthy tissue or blood. 11,12 Therefore, using pH as a trigger for the controlled release of anticancer drugs appears highly advantageous but also feasible. [16][17][18][19][20] Dox-RGD-GQDs were dialyzed in PBS (pH 7.4) for 48 hours to remove unloaded Dox.…”

“…6,7 Furthermore, a nanoparticle's surface can be functionalized with targeting molecules such as arginine-glycine-aspartic acid (RGD), folic acid, or antibodies to improve drug delivery to target tumor cells, which additionally will reduce the side effects of drugs reaching healthy cells. 1,[8][9][10] In general, most nanoparticles are internalized via endocytosis and end up in endo/ lysosomal compartments, 11,12 which are rather acidic (pH 4.5-5.5) in nature compared with the extracellular environment (pH 7.4). 13 Furthermore, some tumors are slightly more acidic than healthy tissue or the blood.…”

Temperature-dependent and time-dependent effects of hyperthermia mediated by dextran-coated La0.7Sr0.3MnO3: in vitro studies

“…The observed internalization of Dex-LSMO nanoparticles could be important for delivery of therapeutic drugs directly into the intercellular compartment, 26 cell tracking, and contrast enhancement in magnetic resonance imaging. 25,27 In our continued efforts, we evaluated induction of heat shock proteins (HSPs) in melanoma cells at different time points (ie, 0, 2, 4, 8, 12, 24, 48, and 72 hours) after treatment with hyperthermia at 43°C. 21 RF-induced Dex-LSMO-mediated hyperthermia resulted in enhanced induction of HSPs as compared with incubator hyperthermia (a model mimicking conventional whole body hyperthermia).…”

New findings about iron oxide nanoparticles and their different effects on murine primary brain cells

“…For instance, positively charged particles interact with the negatively charged glycocalyx, increasing effective and avid particle uptake by mechanisms like clathrin-mediated endocytosis. 28,[61][62][63] Furthermore, the respective surface charge can lead to protein adsorption onto nanoparticles in biological media and affect their agglomeration, as well as accumulation by brain cells. 61,[64][65][66] In our experiments, VSOPs, as the smallest and electrostatically stabilized particles, and ferucarbotran, as the largest and sterically stabilized particles, were rapidly accumulated by microglial cells.…”

“…28,[61][62][63] Furthermore, the respective surface charge can lead to protein adsorption onto nanoparticles in biological media and affect their agglomeration, as well as accumulation by brain cells. 61,[64][65][66] In our experiments, VSOPs, as the smallest and electrostatically stabilized particles, and ferucarbotran, as the largest and sterically stabilized particles, were rapidly accumulated by microglial cells. Internalization of ferucarbotran by active phagocytes like microglia has previously been described, demonstrating that ferucarbotran is taken up by macrophages via clathrin receptor-mediated endocytosis and stored in lysosomal vesicles where the low pH facilitates the degradation of the carboxydextran coat.…”