(A) Representative confocal image of PCL nanoparticles uptake by
control (non-activated) microglia LPS stimulated (activated) microglia
in vitro, (B) Semi-quantification based on
integrated fluorescence intensity demonstrated higher 1.7-fold higher uptake of
particles by LPS stimulated microglia than control microglia. Reprinted
(adapted) with permission from Ref [92].
Copyright (2015) American Chemical Society.
(C–F) Distribution of fluorescent-labeled
generation 4 hydroxyl terminated PAMAM dendrimers (D-Cy5) in a rat brain bearing
9L glioblastoma. D-Cy5 was administrated systemically at day 9 after tumor
inoculation. Confocal images of tumor region suggested that D-Cy5 (~4 nm in
size) uniformly distributed across the 6 mm tumor after 24 hr post
administration. (C), and was co-localized with Iba1+ TAM in tumor
but not in the 'resting' microglia in the contralateral hemisphere of the same
rat brain after 4 hr of D-Cy5 administration (D and
E). Imaging analysis showed almost all D-Cy5+ cells were Iba1+
cells, indicating the high efficiency of TAMs taking up dendrimers
(F) [101]. Green: Iba1+
microglia/macrophages; red: D-Cy5; blue: DAPI; bar: 100 μm. Reprinted
from Biomaterials, Vol 52, F Zhang, et al., Uniform brain tumor
distribution and tumor associated macrophage targeting of systemically
administered dendrimers, 507-516, Copyright (2015), with permission from
Elsevier.