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.

考虑到 CpG 寡脱氧核苷酸 (CpGs) 的有效免疫刺激，CpG 载体的开发是有效癌症免疫治疗的先决条件。在本研究中，我们共轭 1,2-二硬脂酰-sn-glycero-3-phosphoethanolamine-N-[羟基琥珀酰亚胺（聚乙二醇）]（DSPE-PEG-NHS）与聚乙烯亚胺（PEI）开发PEI-PEG-DSPE偶联物，可作为生物相容性和高效的CpG载体。开发了五种类型的 PEIPEG-DSPE 偶联物，每种都具有不同的 PEI 分子量和不同程度的 DSPEPEG 修饰，并且都表现出显着较低的细胞毒性。特别是，与通过天然 PEI 递送 CpG 相比，使用摩尔比为 0.1 的 PEI (25 kDa)-PEG-DSPE 和 DSPE-PEG-NHS/（PEI 的胺基团）递送导致更高的 CpG 摄取到 RAW264 .7 细胞，可能是因为存在疏水性脂质部分。此外，PEI-PEG-DSPE/CpG 复合物触发了 RAW264.7 细胞的显着细胞因子分泌 (TNF-α)，与 PEI/CpG 复合物触发的分泌相当。因此，