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          DSPE-PEG-Cy7 標(biāo)記膠束在體內(nèi)腎臟靶向性及器官分布研究
          發(fā)布時(shí)間:2025-06-24     作者:kx   分享到:


          鏈接:https://aiche.onlinelibrary.wiley.com/doi/full/10.1002/btm2.10173

          作者:黃毅, 蔣凱瑞, 張旭亭, 殷志忠

          節(jié)選:

          為了測(cè)試納米粒子特性對(duì)腎臟靶向性的影響,將 Cy7 標(biāo)記的膠束靜脈注射到 6-7 周大的雄性和雌性 C57B/6J 小鼠體內(nèi),24 小時(shí)后,通過(guò)對(duì)腎臟、腦、肺、心臟、肝臟、脾臟、腸和膀胱的離體成像評(píng)估膠束的積累。將 10 mol% 的 Cy7 包含在膠束中以最大化熒光信號(hào)而不猝滅,并合成了摩爾比為 45:45:10 的 DSPE-PEG-甲氧基:DSPE-PEG-肽:DSPE-PEG-Cy7 或摩爾比為 90:10 的 DSPE-PEG-肽:DSPE-PEG-Cy7 的膠束用于體內(nèi)研究。盡管所有膠束均達(dá)到或超過(guò)報(bào)告的腎臟濾過(guò)截止尺寸,但除 90% PEG5000-(KKEEE) 3 K 外,所有膠束在腎臟中的蓄積程度均大于其他器官。19 90 % PEG5000-(KKEEE) 3 K 具有最高的 PEG 分子量和最大的直徑 17.2 ± 1.8 nm,主要蓄積在肝臟中(1.6 × 10 9 ?± 1.3 × 10 8 ?p/s/cm 2 /sr),可能通過(guò) MPS 系統(tǒng)識(shí)別。然而,這與其在腎臟中的蓄積在統(tǒng)計(jì)學(xué)上并不顯著,這表明它能夠同時(shí)穿過(guò) GFB 并在腎臟中蓄積。盡管膠束的尺寸略大于腎小球?yàn)V過(guò)直徑的截止值(~10 nm),但已發(fā)現(xiàn) 60–100 nm 聚陽(yáng)離子-siRNA 納米顆粒和直徑超過(guò)截止值 8–10 nm 的其他軟大分子會(huì)在腎臟中蓄積并通過(guò)GFB。

          譯文:

          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.

          DSPE-PEG-Cy7

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