DSPE-PEG-NHS介导构建PEI-PEG-DSPE复合物用于高效CpG递送的免疫激活研究
文章：脂质聚乙稀亚胺根据物做为CpG寡脱氧核苷酸动物相溶性媒介对巨噬神经元的评价语跳转：//link.springer.com/article/10.1007/s12257-020-0366-1小说作者：杨智媛，崔恩瑞，尤佳妍&穆慧静 节选：绪论考虑到CpG寡脱氧核苷酸（CpG）有着专业的具有免疫抗体肿瘤神经血神经元刺击功用，开拓CpG各种形式是建立极有效率肝癌具有免疫抗体肿瘤神经血神经元*的先决先决条件。本理论研究将1,2-二硬脂酰-sn-甘油-3-磷酸酒精胺-N-[羟基虎珀酰亚胺（聚乙二醇）] (DSPE-PEG-NHS) 与聚丁二烯亚胺 (PEI) 偶联，开拓出另一种PEI-PEG-DSPE偶联物，能以糊口物相融性的极有效率CpG各种形式。我门开拓了几种PEIPEG-DSPE偶联物，每类偶联物的PEI原子核量差异，DSPEPEG的装饰层面也差异，均体现出有明显较低的肿瘤神经血神经元致毒。具体情况们来说，与采用具有PEI递送CpG相对比，以摩尔比0.1递送PEI (25 kDa)-PEG-DSPE和DSPE-PEG-NHS/（PEI的胺基）可从而导致RAW264.7肿瘤神经血神经元对CpG的吸收率更快，这或许是仍然具有疏水性树脂脂质那部分。不但，PEI-PEG-DSPE/CpG和好物可引导RAW264.7肿瘤神经血神经元有明显分泌液肿瘤神经血神经元因素（TNF-α），其功用与PEI/CpG和好物能比。从而，PEI-PEG-DSPE偶联物能以糊口物相融性的极有效率各种形式，将具有免疫抗体肿瘤神经血神经元刺击剂CpG递送回巨噬肿瘤神经血神经元。AbstractConsidering 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.
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