interaction, arranged with respect to relevant cell types (in vitro) (Sect. 5.3.1) and
blood (in vivo) (Sect. 5.3.2).
5.3.1 In Vitro Interaction of PEC Particles with Cells
Studies on PEC–cell interaction have different aspects and motivation. Very generally, on the one hand an inert influence of PEC particles on cell growth and
differentiation partly under release of drugs is desired, while on the other hand an
active influence like apoptosis of cancer cells is aimed at. Regardless of the specific
scope, cellular and subcellular binding and endocytosis are key events in the
PEC–cell interaction, as for all other nanoparticle systems [162]. This results in
the internalization of the cell plasma membrane with the formation of vesicles that
can capture PEC particles in the extracellular environment and, after a complicated
fusion scenario, direct them to a given intracellular compartment. According to
Courtoy and coworkers [166], three types of endocytosis can be distinguished:
fluid-phase, adsorptive, and receptor-mediated, whereby the first implies unspecific
uptake directly related to the extracellular concentration and the other two
imply more effective specific binding and accumulation at the cell surface
(via glycosylated aminoglycans and sulfated proteoglycans) followed by
internalization.
Interaction of PEC Particles with Cancer Cells
In an early report by Janes et al. [135], the interaction between DOX-loaded PEC
nanoparticles (consisting of CHT and polyanions) and human melanoma cells was
investigated with reference to the polyanion type and preparation protocol. Evidence was found that DOX-loaded PEC particles consisting of DS maintained the
cytostatic activity with respect to free DOX, whereas DOX precomplexed with
CHT before complexation with the polyanion showed slightly decreased activity
(according to the MTT assay). Furthermore, CLSM studies revealed that DOX
release did not take place in the cell culture medium, but that DOX was taken up
into the melanoma cells by endocytosis while still bound to PEC particles and
finally released intracellularly.
Related studies on the cytotoxicity of a CHT/gelatin hydrogel PEC system were
reported by Mao et al. [167]. Fibroblast cell adhesion, proliferation, and apoptosis
were investigated at CHT and CHT/gelatin membranes having different degrees of
deacetylation. This study confirmed that CHT/gelatin induced fibroblasts to enter
the cell cycle and proliferate and decreased their apoptosis, in contrast to pure CHT
membranes, for which the deacetylation degree modulates the undesired cell
adhesion.
In a recent report by Tsai et al. [168], the cytotoxicity of DOX-loaded chitosan/
chondroitin (CHT/CHO) PEC particles to human oral carcinoma and lung carcinoma cells was studied with methacrylate modification and/or crosslinking as
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M. M€ uller
blood (in vivo) (Sect. 5.3.2).
5.3.1 In Vitro Interaction of PEC Particles with Cells
Studies on PEC–cell interaction have different aspects and motivation. Very generally, on the one hand an inert influence of PEC particles on cell growth and
differentiation partly under release of drugs is desired, while on the other hand an
active influence like apoptosis of cancer cells is aimed at. Regardless of the specific
scope, cellular and subcellular binding and endocytosis are key events in the
PEC–cell interaction, as for all other nanoparticle systems [162]. This results in
the internalization of the cell plasma membrane with the formation of vesicles that
can capture PEC particles in the extracellular environment and, after a complicated
fusion scenario, direct them to a given intracellular compartment. According to
Courtoy and coworkers [166], three types of endocytosis can be distinguished:
fluid-phase, adsorptive, and receptor-mediated, whereby the first implies unspecific
uptake directly related to the extracellular concentration and the other two
imply more effective specific binding and accumulation at the cell surface
(via glycosylated aminoglycans and sulfated proteoglycans) followed by
internalization.
Interaction of PEC Particles with Cancer Cells
In an early report by Janes et al. [135], the interaction between DOX-loaded PEC
nanoparticles (consisting of CHT and polyanions) and human melanoma cells was
investigated with reference to the polyanion type and preparation protocol. Evidence was found that DOX-loaded PEC particles consisting of DS maintained the
cytostatic activity with respect to free DOX, whereas DOX precomplexed with
CHT before complexation with the polyanion showed slightly decreased activity
(according to the MTT assay). Furthermore, CLSM studies revealed that DOX
release did not take place in the cell culture medium, but that DOX was taken up
into the melanoma cells by endocytosis while still bound to PEC particles and
finally released intracellularly.
Related studies on the cytotoxicity of a CHT/gelatin hydrogel PEC system were
reported by Mao et al. [167]. Fibroblast cell adhesion, proliferation, and apoptosis
were investigated at CHT and CHT/gelatin membranes having different degrees of
deacetylation. This study confirmed that CHT/gelatin induced fibroblasts to enter
the cell cycle and proliferate and decreased their apoptosis, in contrast to pure CHT
membranes, for which the deacetylation degree modulates the undesired cell
adhesion.
In a recent report by Tsai et al. [168], the cytotoxicity of DOX-loaded chitosan/
chondroitin (CHT/CHO) PEC particles to human oral carcinoma and lung carcinoma cells was studied with methacrylate modification and/or crosslinking as
246
M. M€ uller