DSPE-PEG-NHS调控PEI表面性质以实现低毒性、高效率的CpG递送
文章:脂质聚氯乙烯亚胺依照物作为一个CpG寡脱氧核苷酸生物制品相匹配性质粒载体对巨噬内部的评分链接搜索://link.springer.com/article/10.1007/s12257-020-0366-1我:杨智媛,崔恩瑞,尤佳妍&穆慧静节选:因CpG寡脱氧核苷酸(CpG)包括很强的免役具体实施条件畅快的功效,激发CpG质粒承载是实现了快速益癌病免役*的先决具体实施条件。本学习将1,2-二硬脂酰-sn-甘油-3-磷酸乙酸乙酯胺-N-[羟基蜜腊酰亚胺(聚乙二醇)] (DSPE-PEG-NHS) 与聚丁二烯亚胺 (PEI) 偶联,激发出1种PEI-PEG-DSPE偶联物,可当养家糊口物相融性的快速益CpG质粒承载。企业激发了5种PEIPEG-DSPE偶联物,每款偶联物的PEI氧分子量不一,DSPEPEG的绘制因素也不是一,均主要表现出为正相关较低的组织致毒。具体实施一般说来,与能够天然植物PEI递送CpG相比较,以摩尔比0.1递送PEI (25 kDa)-PEG-DSPE和DSPE-PEG-NHS/(PEI的胺基)可诱发RAW264.7组织对CpG的吸收能力越高,这将是因普遍存在疏水脂质部件。不仅而且,PEI-PEG-DSPE/CpG组合物可诱骗RAW264.7组织为正相关排泌组织分子(TNF-α),其的功效与PEI/CpG组合物该是。因,PEI-PEG-DSPE偶联物可当养家糊口物相融性的快速益质粒承载,将免役具体实施条件畅快剂CpG递送回巨噬组织。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.