4).77 The higher aspect ratios of rod-shaped particles affected the cell functions, such as cellular uptake and apoptosis, in higher extent than sphere-shaped particles. Figure 4. (A) Quantification of cellular uptake and apoptosis of different shaped PSiO2 by flow cytometry analysis of different prepared PSiO2 nanoparticles: sphere-shaped, NS (100 nm), short rod-shaped, NSR Tofacitinib Citrate order (240 nm) and long rod-shaped, NLR (450 … Cellular uptake and trafficking In order to understand the response of biological cells to nanoparticles, it is crucial to learn about the mechanisms of cellular uptake and intracellular trafficking.10 The cell membrane is a complex system consisting of lipids, proteins, cholesterol and receptors, which presents a net negative surface charge.
16 Hence, the surface potential of the nanocarrier as well as the receptors attached to the cell membrane are the features that define cell uptake and trafficking in animal cells. Moreover, it has been demonstrated that the cell uptake of nanoparticles, besides depending on the dosage and time, also depends on the cell type,80 particle size,81 shape,77 surface charge45 and surface chemistry.82 Concerning the size of the nanoparticles, there are some studies that link the size of different vehicles with cell uptake and from which it can be deduced that depending on the cell line, the size limits for endocytosis of particles may vary.45,83-86 Particles smaller than 200 nm are internalized by cells through endocytic mechanisms, while bigger particles when internalized they are uptaked by either endocytosis or phagocytosis.
Regarding the PSiO2 nanoparticles, several studies have been reported describing the relationship between particle size, surface modifications and targeting moieties, and cellular uptake.23 PSiO2 nanoparticle uptake was found to take place via a clarthrin-mediated endocytosis, but the surface modifications of the particles led to different endocytosis mechanisms, e.g., amine- and guanidinium-functionalized PSiO2 nanoparticles suffered a clarthrin and caveolae-independent endocytosis, while folic acid (FA)-functionalized PSiO2 nanoparticles experienced a FA receptor-mediated endocytosis, which increased particles�� uptake by cancer cells.24,53,87 In addition, it has been demonstrated that FITC-PSiO2 nanoparticle internalization is also cell type-, concentration- and time-dependent.
80,87 Lu et al. further demonstrated the energy dependency of the uptake process by showing the higher particle uptake efficiency of cells at 37��C compared with 4��C, and the effect of some metabolic inhibitors in surpressing the PSiO2 nanoparticle uptake in human pancreatic cells.46 PSiO2 nanoparticle endocytosis Anacetrapib and intracellular trafficking pathways have been followed by confocal fluorescence microscopy.45,80,88 The endocytosis led to the formation of a vesicle which captured the particles and internalized them into the cytosol rendering an endosome.