Department of Biomedical Engineering, Duke University, Durham, NC 27708, USA.
Cancer Gene Ther. 2011 Jan;18(1):26-33. doi: 10.1038/cgt.2010.51. Epub 2010 Sep 17.
Pulsed electric fields can enhance interstitial transport of plasmid DNA (pDNA) in solid tumors. However, the extent of enhancement is still limited. To this end, the effects of cellular resistance to electric field-mediated gene delivery were investigated. The investigation used two tumor cell lines (4T1 (a murine mammary carcinoma) and B16.F10 (a metastatic subline of B16 murine melanoma)) either in suspensions or implanted in two in vivo models (dorsal skin-fold chamber (DSC) and hind leg). The volume fraction of cells was altered by pretreatment with a hyperosmotic mannitol solution (1 M). It was observed that the pretreatment reduced the volumes of 4T1 and B16.F10 cells, suspended in an agarose gel, by 50 and 46%, respectively, over a 20-min period, but did not cause significant changes ex vivo in volumes of hind-leg tumor tissues grown from the same cells in mice. The mannitol pretreatment in vivo improved electric field-mediated gene delivery in the hind-leg tumor models, in terms of reporter gene expression, but resulted in minimal enhancement in pDNA electrophoresis over a few microns distance in the DSC tumor models. These data demonstrated that hyperosmotic mannitol solution could effectively improve electric field-mediated gene delivery around individual cells in vivo by increasing the extracellular space.
脉冲电场可以增强实体瘤中质粒 DNA（pDNA）的间质转运。然而，增强的程度仍然有限。为此，研究了细胞对电场介导基因传递的抗性的影响。该研究使用两种肿瘤细胞系（4T1（一种鼠乳腺肿瘤）和 B16.F10（B16 鼠黑色素瘤的转移亚系）），无论是在悬浮液中还是在两种体内模型（背部皮肤褶皱室（DSC）和后腿）中植入。通过用高渗甘露醇溶液（1M）预处理来改变细胞的体积分数。观察到，在 20 分钟的时间内，甘露醇预处理分别将悬浮在琼脂糖凝胶中的 4T1 和 B16.F10 细胞的体积减少了 50%和 46%，但不会导致从小鼠中相同细胞生长的后腿肿瘤组织的体积在离体时发生显著变化。甘露醇在体内的预处理改善了后腿肿瘤模型中的电场介导基因传递，表现在报告基因表达方面，但在 DSC 肿瘤模型中，仅在几微米的距离内对 pDNA 电泳有微小的增强。这些数据表明，高渗甘露醇溶液可以通过增加细胞外空间，有效地提高体内单个细胞周围电场介导的基因传递。
