DSPE-PEG-NHS介導(dǎo)的CpG遞送系統(tǒng)設(shè)計(jì)與免疫活性評(píng)價(jià)

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

作者：Jiwon Yang, Eun Seo Choi, Gayeon You & Hyejung Mok 

摘要：

鑒于CpG寡脫氧核苷酸（CpG）具有強(qiáng)大的免疫刺激作用，開發(fā)CpG載體是實(shí)現(xiàn)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(lián)，開發(fā)出一種PEI-PEG-DSPE偶聯(lián)物，可作為生物相容性的高效CpG載體。我們開發(fā)了五種PEIPEG-DSPE偶聯(lián)物，每種偶聯(lián)物的PEI分子量不同，DSPEPEG的修飾程度也不同，均表現(xiàn)出顯著較低的細(xì)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(dǎo)致RAW264.7細(xì)胞對(duì)CpG的吸收更高，這可能是由于存在疏水性脂質(zhì)部分。此外，PEI-PEG-DSPE/CpG復(fù)合物可誘導(dǎo)RAW264.7細(xì)胞顯著分泌細(xì)胞因子（TNF-α），其作用與PEI/CpG復(fù)合物相當(dāng)。因此，PEI-PEG-DSPE偶聯(lián)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(xì)胞。

譯文：

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pg電子官方生物提供相關(guān)產(chǎn)品：

DSPE-PEG-VIP(二硬脂�；�磷脂酰乙醇胺-聚乙二醇-*血管活性腸肽)

DSPE-PEG-GE11(二硬脂�；�磷脂酰乙醇胺-聚乙二醇-*細(xì)胞表皮生長(zhǎng)因子EGFR靶向肽)

DSPE-PEG-PTP(二硬脂酰基磷脂酰乙醇胺-聚乙二醇-胰腺癌靶向肽)

DSPE-PEG-FSHB(二硬脂�；�磷脂酰乙醇胺-聚乙二醇-卵巢癌靶向肽)

DSPE-PEG-R6H4（二硬脂酰基磷脂酰乙醇胺-聚乙二醇-PH響應(yīng)性細(xì)胞穿膜肽)

DSPE-PEG-SEARYL-R8（二硬脂�；�磷脂酰乙醇胺-聚乙二醇-PH響應(yīng)性細(xì)胞穿膜肽)

DSPE-PEG-SEARYL-PF6（二硬脂�；�磷脂酰乙醇胺-聚乙二醇-PH響應(yīng)性細(xì)胞穿膜肽)

DSPE-PEG-TH（二硬脂酰基磷脂酰乙醇胺-聚乙二醇-PH響應(yīng)性細(xì)胞穿膜肽)

DSPE-PEG-OTC（二硬脂�；�磷脂酰乙醇胺-聚乙二醇-生長(zhǎng)抑索受體靶向肽)

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