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

文獻鏈接：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).

用不同的表面涂層制備了小于100 nm的siRNA NP

基于PLGA的siRNA NP具有五種不同的表面涂層，通過多種機制與BBB和神經細胞相互作用。將與1,2-二硬脂�；�-sn-甘油-3-磷酸乙醇胺（DSPE）共軛的聚乙二醇（PEG）摻入NP中，以實現(xiàn)“隱形”效應，延長其體循環(huán)時間。

具體來說，我們選擇了聚山梨酯80（PS 80）、泊洛沙姆188（Pluronic F-68）、DSPE-PEG谷胱甘肽（GSH）和DSPE-PEG轉鐵蛋白（Tf）。PS 80和F-68之前已被證明可以通過與內源性載脂蛋白結合并與BBB上的脂蛋白受體相互作用來促進藥物通過BBB的遞送。

GSH是一種已進入2期臨床試驗的BBB穿梭肽，可以通過GSH轉運蛋白將NP轉運通過BBB。Tf已被證明通過與腦內皮上表達的Tf受體結合來促進NP的腦遞送。

相關推薦：

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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