文献：BBB pathophysiology–independent delivery of siRNA in traumatic brain injury

文献链接：https://www.science.org/doi/full/10.1126/sciadv.abd6889

摘要：

Sub–100-nm-sized siRNA NPs were prepared with different surface coatings

PLGA-based siRNA NPs with five different surface coatings were engineered to interact with BBB and neural cells by a variety of mechanisms. Polyethylene glycol (PEG) conjugated to 1,2-distearoyl-sn-glycero-3-phosphoethanolamine (DSPE) was incorporated in NPs for “stealth” effect to extend their systemic circulation time (29). In addition to DSPE-PEG, we also included one of the four different surface coatings that have previously shown to augment active penetration of NPs across BBB in other diseases. Specifically, we chose polysorbate 80 (PS 80), poloxamer 188 (Pluronic F-68), DSPE-PEG-glutathione (GSH), and DSPE-PEG-transferrin (Tf). PS 80 and F-68 have been previously shown to promote drug delivery across BBB by binding to endogenous apolipoproteins and interacting with lipoprotein receptors on BBB (30–32). GSH, a BBB shuttle peptide that has reached phase 2 clinical trials, can transport NPs through BBB via GSH transporters (33, 34). Tf has been shown to facilitate brain delivery of NPs by binding to Tf receptors expressed on brain endothelium (35, 36).

用不同的表面涂层制备了小于100 nm的siRNA NP

基于PLGA的siRNA NP具有五种不同的表面涂层，通过多种机制与BBB和神经细胞相互作用。将与1,2-二硬脂酰基-sn-甘油-3-磷酸乙醇胺（DSPE）共轭的聚乙二醇（PEG）掺入NP中，以实现“隐形”效应，延长其体循环时间。

具体来说，我们选择了聚山梨酯80（PS 80）、泊洛沙姆188（Pluronic F-68）、DSPE-PEG谷胱甘肽（GSH）和DSPE-PEG转铁蛋白（Tf）。PS 80和F-68之前已被证明可以通过与内源性载脂蛋白结合并与BBB上的脂蛋白受体相互作用来促进药物通过BBB的递送。

GSH是一种已进入2期临床试验的BBB穿梭肽，可以通过GSH转运蛋白将NP转运通过BBB。Tf已被证明通过与脑内皮上表达的Tf受体结合来促进NP的脑递送。

相关推荐：

DSPE-PEG-SG

DSPE-PEG-SH

DSPE-PEG-Silane

DSPE-PEG-SP2-AA

DSPE-PEG-SS

DSPE-PEG-TCO

DSPE-PEG-Tetrazine

DSPE-PEG-TMS

DSPE-PEG-TPP

DSPE-PEG-Transferrin 

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