Biomedical Engineering Reference
In-Depth Information
Fig. 14 Maturation and activation of DCs by nanoparticles
nanoparticles mediates the phenotypic maturation of DCs, the DCs were incubated
with
g
-PGA-Phe nanoparticles for 24 or 48 h, and the expression of surface
molecules was measured by fluorescence confocal microscopy (FCM). Upon
exposure of these DCs to the nanoparticles, the expression of co-stimulatory
molecules (maturation markers) was increased in a dose-dependent manner. The
expression levels of co-stimulatory molecules in nanoparticle-pulsed DCs were
similar to those of LPS-pulsed DCs. These results suggest that
g
-PGA-Phe
nanoparticles have great potential as adjuvant for DC maturation [
62
,
102
,
103
].
The mechanisms responsible for DC maturation by
g
-PGA-Phe nanoparticles are
still unclear. However, it is hypothesized that not only the uptake of nanoparticles
but also the characteristics of the polymers forming the nanoparticles are impor-
tant for the induction of DC maturation. The DC uptake of 30 nm-sized
nanoparticles was lower than for 200 nm-sized nanoparticles, but the effect of
DC activation by the nanoparticles was high for the small sizes [
116
,
117
]. Thus,
it is considered that the surface interactions between the nanoparticles and DCs
predominately affect DC maturation. In addition, soluble
g
-PGA-induced innate
immune responses in a Toll-like receptor 4 (TLR4)-dependent manner in DCs
have been reported [
118
,
119
]. TLRs are abundantly expressed on professional
APCs. TLRs play a major role in pathogen recognition, and in the initiation of the
inflammatory and immune responses. The stimulation of TLRs by TLR ligands
induces the surface expression of co-stimulatory molecules, and this phenotypic
modulation is a typical feature of DC maturation. Treatment with high molecular
weight
g
-PGA (2,000 kDa), but not low molecular weight
g
-PGA (10 kDa)
induced a significant upregulation of CD40, CD80, and CD86 expression in
wild-type DCs. The stimulatory capacity of
g
-PGA was not significantly affected
by pretreatment with Polymyxin B (PmB). In contrast, DCs from TLR4-defective
mice did not show an enhanced expression of maturation markers in response to
the 2,000 kDa
g
-PGA treatment. It is suggested that the
g
-PGA-Phe nanoparticles
also induce DC maturation in a TLR4-dependent manner using the same
2,000 kDa
g
-PGA, because
g
-PGA is located near the nanoparticle surface.
