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2017 ; 12
(ä): 6383-6398
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Intracellular disposition of chitosan nanoparticles in macrophages: intracellular
uptake, exocytosis, and intercellular transport
#MMPMID28919742
Jiang LQ
; Wang TY
; Webster TJ
; Duan HJ
; Qiu JY
; Zhao ZM
; Yin XX
; Zheng CL
Int J Nanomedicine
2017[]; 12
(ä): 6383-6398
PMID28919742
show ga
Biodegradable nanomaterials have been widely used in numerous medical fields. To
further improve such efforts, this study focused on the intracellular disposition
of chitosan nanoparticles (CsNPs) in macrophages, a primary cell of the
mononuclear phagocyte system (MPS). Such interactions with the MPS determine the
nanoparticle retention time in the body and consequently play a significant role
in their own clinical safety. In this study, various dye-labeled CsNPs (about 250
nm) were prepared, and a murine macrophage cell line (RAW 264.7) was selected as
a model macrophage. The results showed two mechanisms of macrophage incorporation
of CsNPs, ie, a clathrin-mediated endocytosis pathway (the primary) and
phagocytosis. Following internalization, the particles partly dissociated in the
cells, indicating cellular digestion of the nanoparticles. It was proved that,
after intracellular uptake, a large proportion of CsNPs were exocytosed within 24
h; this excretion induced a decrease in fluorescence intensity in cells by 69%,
with the remaining particles possessing difficulty being cleared. Exocytosis
could be inhibited by both wortmannin and vacuolin-1, indicating that CsNP uptake
was mediated by lysosomal and multivesicular body pathways, and after exocytosis,
the reuptake of CsNPs by neighboring cells was verified by further experiments.
This study, thus, elucidated the fate of CsNPs in macrophages as well as
identified cellular disposition mechanisms, providing the basis for how CsNPs are
recognized by the MPS; such information is crucial to numerous medical
applications of CsNPs.
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