文獻：脂質聚乙烯亞胺結合物作為CpG寡脫氧核苷酸生物相容性載體對巨噬細胞的評價

鏈接：https://link.springer.com/article/10.1007/s12257-020-0366-1

作者：楊智媛，崔恩瑞，尤佳妍&穆慧靜

節選：

鑒于CpG寡脫氧核苷酸（CpG）具有強大的免疫刺激作用，開發CpG載體是實現高效癌癥免疫*的先決條件。本研究將1,2-二硬脂酰-sn-甘油-3-磷酸乙醇胺-N-[羥基琥珀酰亞胺（聚乙二醇）] (DSPE-PEG-NHS) 與聚乙烯亞胺 (PEI) 偶聯，開發出一種PEI-PEG-DSPE偶聯物，可作為生物相容性的高效CpG載體。我們開發了五種PEIPEG-DSPE偶聯物，每種偶聯物的PEI分子量不同，DSPEPEG的修飾程度也不同，均表現出顯著較低的細胞毒性。具體而言，與通過天然PEI遞送CpG相比，以摩爾比0.1遞送PEI (25 kDa)-PEG-DSPE和DSPE-PEG-NHS/（PEI的胺基）可導致RAW264.7細胞對CpG的吸收更高，這可能是由于存在疏水性脂質部分。此外，PEI-PEG-DSPE/CpG復合物可誘導RAW264.7細胞顯著分泌細胞因子（TNF-α），其作用與PEI/CpG復合物相當。因此，PEI-PEG-DSPE偶聯物可作為生物相容性的高效載體，將免疫刺激劑CpG遞送至巨噬細胞。

Abstract

Considering the potent immune stimulation by CpG oligodeoxynucleotides (CpGs), the development of CpG carriers is a prerequisite for efficient cancer immunotherapy. In this study, we conjugated 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[hydroxyl succinimidyl (polyethylene glycol)] (DSPE-PEG-NHS) with polyethylenimine (PEI) to develop a PEI-PEG-DSPE conjugate that can serve as a biocompatible and efficient CpG carrier. Five types of PEIPEG-DSPE conjugates were developed, each with different molecular weights of PEI and different degrees of DSPEPEG modification, and all exhibited significantly lower cytotoxicity. In particular, compared to CpG delivery via natural PEI, delivery with PEI (25 kDa)-PEG-DSPE and DSPE-PEG-NHS/(amine groups of PEI) at a molar ratio of 0.1 resulted in a higher uptake of CpGs into RAW264.7 cells, probably because of the presence of a hydrophobic lipid moiety. In addition, PEI-PEG-DSPE/CpG complexes triggered significant cytokine secretion (TNF-α) from RAW264.7 cells, comparable to that triggered by PEI/CpG complexes. Thus, PEI-PEG-DSPE conjugates could serve as biocompatible and efficient carriers of the immune stimulator CpG to the macrophages.

西安齊岳生物提供相關產品：

DSPE-PLGA

cRGD(c[RGDfc])-PEG-DSPE

DSPE-PEG-THRPPMWSPVWP（二硬脂酰基磷脂酰乙醇胺-聚乙二醇-轉鐵蛋白靶向肽)

C18-PEG-COOH

CPP-PEG-DSPE

m-PEG12-DSPE

DSPE-PEG-CCK8

mPEG-DMPE

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