The Key Laboratory of Stem Cell Biology, Shanghai Jiao Tong University School of Medicine (SJTUSM) & Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS), Shanghai, PR China.
Biomaterials. 2012 Sep;33(27):6520-32. doi: 10.1016/j.biomaterials.2012.05.044. Epub 2012 Jun 12.
Cytoxicity is an essential concern for polyethyleneimine 25 kDa (PEI 25 kDa), a widely reported, highly effective transfection agent used in gene delivery. In our recent experiments, Small molecular weight cross-linked poly(ethylene imine) by biscarbamate linkage (PEI-Bu) (Mn: 3278, Mw: 4289) can reduce target cell apoptosis induced by polycationic transfection, and has almost the same DNA condensation capability as PEI 25 kDa. PEI-Bu showed significantly higher activity and lower cytotoxicity than PEI 25 kDa in transfecting the anti-inflammatory cytokine interleukin-1 receptor antagonist (IL-1Ra) gene to rat synoviocytes, an optimal target for arthritis treatment. The expression of IL-1Ra in synoviocytes then suppresses the expression of metalloproteases 13 (MMP13) gene, which is responsible for cartilage destruction regulated by IL-1β in arthritis. In conclusion, PEI-Bu is a promising tool for delivering IL-1Ra gene to synoviocytes for arthritis therapy.
细胞毒性是聚乙烯亚胺 25kDa（PEI 25kDa）的一个重要关注点，PEI 25kDa 是一种广泛报道的、高效的转染试剂，用于基因传递。在我们最近的实验中，小分子交联的聚（亚乙基亚胺）通过双碳酸酯键（PEI-Bu）（Mn：3278，Mw：4289）可以减少由聚阳离子转染引起的靶细胞凋亡，并且具有与 PEI 25kDa 几乎相同的 DNA 凝聚能力。PEI-Bu 在转染抗炎细胞因子白细胞介素-1 受体拮抗剂（IL-1Ra）基因到大鼠滑膜细胞中时，表现出比 PEI 25kDa 更高的活性和更低的细胞毒性，滑膜细胞是关节炎治疗的最佳靶标。滑膜细胞中 IL-1Ra 的表达继而抑制金属蛋白酶 13（MMP13）基因的表达，MMP13 基因负责由 IL-1β 调节的关节炎中的软骨破坏。总之，PEI-Bu 是一种有前途的工具，可将 IL-1Ra 基因递送到滑膜细胞中用于关节炎治疗。
