b2815 Tissue Engineering and Nanotheranostics “9.61x6.69”
232 Tissue Engineering and Nanotheranostics
easily taken up by reticuloendothelial systems. It has been found that
nanomaterials with the size of ca. 50 nm have a maximum uptake
in vitro,^79 while a general range of 10–100 nm has been demonstrated
for in vivo applications.^80 The nanomaterials with less than 10 nm in
size or larger size are cleared via glomerular filtration in the kidneys,^81
the Kupffer cells of the liver and through the spleen,^82 respectively. In
tumor targeting application, the nanomaterials with the size range
between 50 and 150 nm are more appropriate no matter active or
passive targeting, while anything larger than 400 nm is considered too
large.83,84
Effect of shape. The shape of nanomaterials has a significant
impact on the internalization interaction between the particles and
cells.^85 The selected nanomaterials with a suitable shape are conducive
to obtain high effect on the circulation time, in vivo distribution, and
residency time inside the cancer. Moreover, the effect of targeting the
desired cells can be acquired by controlling the shape of nanomateri
als. Also, the shape of nanomaterials can also affect their receptor
mediated endocytosis.^86 Generally, the elongated nanocarriers exhibit
higher efficiency in adhering to the cells rather than the nanospheres.
The rods show higher affinity and efficiency to the endothelial cells in
in vitro experiments. In vivo studies indicated that spheres with the
constant forces acting on them often remain in the center of the
blood vessel as they circulate.^87 Rods easily accumulate at the vessel
walls because of asymmetrical shape susceptible to drag forces and
torques as they circulate. Shape is also an important factor affecting
circulation time and biodistribution of the nanomaterials. According
to the reports, the long circulation time of spheres is shorter than
those of nonspherical nanomaterials.^88
Effect of charge. Negative membrane of cells interacting differ
ently with positively/negatively charged nanomaterials is important in
interpretation of mechanism and designing of suitable nanocarriers.
Due to electrostatic interaction with the negative cell membrane, the
positively charged nanomaterials show higher uptake than negatively
charged ones through endocytosis pathways.89–94 Previous studies
showed that internalization of nanoparticles with negative charge
surface decreases by increasing of surface charge, but the amount of
