National University of Science and Technology (MISIS), Moscow 119049, Russia.
National University of Science and Technology (MISIS), Moscow 119049, Russia; M.V. Lomonosov Moscow State University, Moscow 119991, Russia.
J Control Release. 2019 Aug 10;307:368-378. doi: 10.1016/j.jconrel.2019.06.026. Epub 2019 Jun 25.
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 h 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.
开发能够在靶向器官中积累且无害消除的纳米载体仍然是一个巨大的挑战。纳米颗粒（NP）的生物分布受其大小、组成、表面电荷和覆盖率的影响。目前的生物纳米技术认为，肾脏清除受到肾小球基底膜孔大小（≈6nm）的限制，尽管越来越多的证据表明，超过阈值的 NP 也可以随尿液排出。在这里，我们比较了聚乙二醇化 140nm 氧化铁立方体和团簇的生物分布，特别关注肾脏的积累和排泄。原子发射光谱、荧光显微镜和磁共振成像显示，磁性 NP 迅速且短暂地在肾脏中积累。我们使用活体显微镜实时跟踪 NP 从肾小管周围毛细血管向管状细胞基底部的易位，并在系统给药后 60 分钟内将其排泄到管腔中。透射电子显微镜显示，在注射后 2 小时的尿液中仍存在完整的全尺寸 NP。这些结果表明，通过肾小管周围内皮向肾小管上皮细胞的易位是一种肾脏清除的替代机制，使超过肾小球截止尺寸的 NP 能够排出体外。
