链接:https://aiche.onlinelibrary.wiley.com/doi/full/10.1002/btm2.10173
作者:黄毅, 蒋凯瑞, 张旭亭, 殷志忠
节选:
为了测试纳米粒子特性对肾脏靶向性的影响,将 Cy7 标记的胶束静脉注射到 6-7 周大的雄性和雌性 C57B/6J 小鼠体内,24 小时后,通过对肾脏、脑、肺、心脏、肝脏、脾脏、肠和膀胱的离体成像评估胶束的积累。将 10 mol% 的 Cy7 包含在胶束中以最大化荧光信号而不猝灭,并合成了摩尔比为 45:45:10 的 DSPE-PEG-甲氧基:DSPE-PEG-肽:DSPE-PEG-Cy7 或摩尔比为 90:10 的 DSPE-PEG-肽:DSPE-PEG-Cy7 的胶束用于体内研究。尽管所有胶束均达到或超过报告的肾脏滤过截止尺寸,但除 90% PEG5000-(KKEEE) 3 K 外,所有胶束在肾脏中的蓄积程度均大于其他器官。19 90 % PEG5000-(KKEEE) 3 K 具有最高的 PEG 分子量和最大的直径 17.2 ± 1.8 nm,主要蓄积在肝脏中(1.6 × 10 9 ± 1.3 × 10 8 p/s/cm 2 /sr),可能通过 MPS 系统识别。然而,这与其在肾脏中的蓄积在统计学上并不显著,这表明它能够同时穿过 GFB 并在肾脏中蓄积。尽管胶束的尺寸略大于肾小球滤过直径的截止值(~10 nm),但已发现 60–100 nm 聚阳离子-siRNA 纳米颗粒和直径超过截止值 8–10 nm 的其他软大分子会在肾脏中蓄积并通过GFB。
译文:
To test the effects of nanoparticle characteristics on renal targeting, Cy7-labeled micelles were intravenously administered into 6–7 week old male and female C57B/6 J mice and after 24 hours, micelle accumulation was assessed via ex vivo imaging of the kidneys, brain, lung, heart, liver, spleen, intestine, and bladder. 10 mol% of Cy7 was included into micelles to maximize the fluorescence signal without quenching and micelles with 45:45:10 molar ratio of DSPE-PEG-methoxy:DSPE-PEG-peptide:DSPE-PEG-Cy7 or 90:10 molar ratio of DSPE-PEG-peptide:DSPE-PEG-Cy7 were synthesized for in vivo studies. despite all micelles being at or above the reported renal filtration cut-off size, all micelles accumulated in the kidneys to a greater extent than all other organs with the exception of 90% PEG5000-(KKEEE)3K .19 90% PEG5000-(KKEEE)3K, which had the highest PEG molecular weight and largest diameter of 17.2 ± 1.8 nm (Table 1), mostly accumulated in the liver (1.6 × 109 ± 1.3 × 108 p/s/cm2/sr) likely via recognition of the MPS system . However, this was not statistically significant with its accumulation in the kidneys, which indicates an ability to simultaneously pass through the GFB and accumulate in the kidneys (Figures S2 and S3). Although the size of micelles was slightly larger than the cut-off diameter of glomerular filtration (~10 nm), kidney accumulation and passage through the GFB has been found for 60–100 nm polycation-siRNA nanoparticles and other soft macromolecules with the diameter beyond the cut-off size of 8–10 nm.
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