Human Toxicology and Effects of Nanoparticles - Environmental and Human Health Impacts of Nanotechnology - page 361

cell. For example, charge infl uences the uptake of cationic molecules, which are
strongly attracted to the cell surface due to the non-specifi c electrostatic interac-
tions that occur with the negative charge of the plasma membrane interior (Patel
et al. , 2007). It is worth noting that charged molecules cannot pass through the
plasma membrane simply via diffusion. It is conceivable that this membrane poten-
tial could provide a driving force to drive positively charged particles to move into
the cell. Whether nanoparticles have the ability to move into cells via diffusion is
currently unclear. A study by Geiser et al. (2005) found that TiO 2 particles were
located inside lung cells following inhalation. The EM images used to image the
TiO 2 suggested that plasma membrane was not clearly distinguishable around the
nanoparticles, from which the authors concluded that uptake could be via a non-
endocytic pathway such as diffusion. However, much more evidence is required
before diffusion is widely accepted as a viable uptake route for nanoparticles into
cells.
Facilitated diffusion allows substances to pass from an area of high to low
concentration through selective membrane protein channels; for this process
energy is not directly required, as it is usually driven by a chemical concentration
gradient. The carrier proteins and channels can be opened or closed depending on
the cells needs, such examples include ligand and voltage gated ion channels.
Movement of nanoparticles into the cell via such channels would require the
particles to be as small as the channel pore size, often in the region of 100- 300 Å
(10- 30 nm).
Active transport of substances across the membrane is conducted by proteins and
occurs against a concentration gradient using energy in the form of ATP. Transpor-
ter structure is very specifi c for the molecules to be actively transported, and there-
fore it is unlikely that nanoparticles could use this as a route of entry into the cell.
The most likely route of uptake of nanoparticles (and larger particles) into cells
is via endocytosis . This is a route of cell entry used for larger molecules and par-
ticles. Endocytosis involves incorporating molecules or particles into membrane
bound vesicles derived from the invagination or pinching-off of the plasma mem-
brane (Conner and Schmid, 2003; Watts and Marsh, 1992). Endocytosis is in fact a
collective term that includes phagocytosis, clathrin mediated endocytosis, caveolae
mediated endocytosis as well as clathrin and caveolae independent endocytosis
(Conner and Schmid, 2003). The size of the vesicles formed for each pathway
differs, for example clathrin coated pits are approximately 120 nm in diameter while
caveolae are 50-80 nm and micropinosomes are generally 1- 5 m (Patel et al. ,

2007). Although these ranges are not defi nitive, it is likely that size limits exist to
restrict the cargo dimensions internalised (Patel et al. , 2007 ).

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9.2.5 Interaction of Nanoparticles with Defence Mechanisms

Phagocytosis is, of course, the process of cell uptake used by defensive cells of the
immune system such as macrophages and neutrophils, also known as professional
phagocytes (Conner and Schmid, 2003). These cells take up relatively large materi-
als (greater than 0.5 m) such as bacteria or cell debris (Khalil et al. 2006 ). During

phagocytosis, the cell recognises ligands via cell surface receptors. Receptor binding

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