Intravital microscopy reveals a novel mechanism of nanoparticles excretion in kidneyстатья
Статья опубликована в высокорейтинговом журнале
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Дата последнего поиска статьи во внешних источниках: 11 ноября 2019 г.
Аннотация:Developing nanocarriers that accumulate in targeted organs and are harmlessly
eliminated still remains a big challenge. Nanoparticles (NP) biodistribution is governed by
their size, composition, surface charge and coverage. The current thinking in
bionanotechnology is that renal clearance is limited by glomerular basement membrane pore
size (≈6 nm), although there is a growing evidence that NP exceeding the threshold can also
be excreted with urine. Here we compare biodistribution of PEGylated 140 nm iron oxide
cubes and clusters with a special focus on renal accumulation and excretion. Atomic emission
spectroscopy, fluorescent microscopy and magnetic resonance imaging revealed rapid and
transient accumulation of magnetic NP in kidney. Using intravital microscopy we tracked in
real time NP translocation from peritubular capillaries to basal compartment of tubular cells
and subsequent excretion to the lumen within 60 min after systemic administration.
Transmission electron microscopy revealed persistence of intact full-sized NP in urine 2
hours post injection. The results suggest that translocation through peritubular endothelium to
tubular epithelial cells is an alternative mechanism of renal clearance enabling excretion of
NP above glomerular cut-off size.