4. Conclusions
In general, the research on
nanoparticle cell internalization mechanism is very beneficial to
improve the therapeutic efficiency of nanomaterial drug delivery
systems. Both the nanoparticle and the cell membrane contain diverse
chemical components and complex physical properties. Therefore, the
effect of the properties of nanoparticles and cell membranes on the
interaction is the hot-spot in this field. This article reviews the
research on the factors affecting the internalization mechanism of
nanoparticle in recent years and summarizes the positive and negative
influence of multiple physical and chemical properties of nanoparticles,
which will assist researchers to propose more reasonable nanoparticle
design solutions:
(1) Nanoparticle size. Small size nanoparticles can smoothly penetrate
cell membranes without causing significant cell membrane deformation.
However, it also brings a lower number of surface ligands and a higher
cell membrane bending energy barrier, thus properly increasing the
nanoparticle size can increase the internalization efficiency. Hence,
researchers should balance the relationship between cytotoxicity and
membrane bending energy to determine the optimal size of nanoparticles.
(2) Nanoparticle shape. The asymmetrical shape (rod, ellipse, disc,
etc.) nanoparticles are conducive to the penetration of cell membranes
and have a special endocytosis dynamic:
orientation-wrapping-reorientation. Compared with the isotropic shape
(spherical, etc.) nanoparticles, this exceptional internalization
kinetics results in a longer internalization time, but its conformation
can be optimized to reduce the curvature of the cell membrane due to the
orientation process which can also promote the wrapping of cell
membranes.
(3) Nanoparticle surface properties. Hydrophobic nanoparticles can be
embedded in the middle layer of the cell membrane, while hydrophilic
nanoparticles can only be adsorbed on the surface. Therefore,
researchers should reasonably adjust the ratio and distribution of the
hydrophilic / hydrophobic surface of the nanoparticles. The density,
length, and type of ligands on the nanoparticle surface will also affect
the nanoparticle-cell membrane interaction mechanism, thereby changing
the degree of nanoparticle encapsulation by the cell membrane. Moreover,
since cancer cells usually contain a higher negative charge density, the
charge distribution on the nanoparticle surface will also provide a
greater driving force.
(4) Nanoparticle concentration. A high concentration of nanoparticles
can form aggregates, increasing the size and adjusting the shape of the
aggregates so that the nanoparticles can enter the cell together under
the synergistic effect of the partner nanoparticles. Understanding the
nanoparticle diffusion kinetics can support researchers in understanding
the deep-depth mechanism of concentration effects.
(5) Nanoparticle elastic modulus. The nanoparticles with low elastic
modulus are more difficult to internalize by cells due to additional
deformation energy. However, a suitable elastic modulus can allow
nanoparticles to flexibly modify their shape, thereby enhancing the cell
internalization probability.