Coll J L, Chollet P, Brambilla E, Desplanques D, Behr J P, Favrot M
Lung Cancer Research Group, Institut Albert Bonniot, Université Joseph Fourier, Grenoble, France.
Hum Gene Ther. 1999 Jul 1;10(10):1659-66. doi: 10.1089/10430349950017662.
Synthetic gene delivery vectors have shown promise in several organs, including brain and lung. Tumor cell targeting, however, is still hindered by their low efficacy. A linear polyethylenimine (L-PEI, Exgen 500) was found to be effective in vivo. Our first attempts to use L-PEI for intratumoral gene delivery were not successful, presumably because of poor diffusion of the complexes within the tumor mass after injection with a syringe. Here we show that L-PEI-mediated transfection can be strongly enhanced when the complexes are delivered slowly into a solid tumor mass, using a micropump. Furthermore, L-PE/DNA complexes actively transfect pseudocystic tumor cells when injected into the cyst cavity. In both cases L-PEI induced a significant and long-lasting (> or =15 days) expression of the reporter gene. Finally, even though systemic delivery of L-PEI/DNA complexes leads to high levels of expression in the lung, this method is not adapted for transfection of subcutaneous tumors implanted in the thigh nor for transfection of lung metastases. Altogether, these results show that L-PEI has promising features for transfection of tumor cells, provided that the mode of delivery is adapted.
合成基因递送载体已在包括脑和肺在内的多个器官中显示出应用前景。然而，其低效率仍然阻碍了肿瘤细胞靶向。发现线性聚乙烯亚胺（L-PEI，Exgen 500）在体内有效。我们首次尝试使用L-PEI进行瘤内基因递送未成功，可能是因为用注射器注射后复合物在肿瘤块内扩散不佳。在此我们表明，当使用微泵将复合物缓慢递送至实体肿瘤块中时，L-PEI介导的转染可得到显著增强。此外，将L-PEI/DNA复合物注入囊腔时可有效转染假性囊性肿瘤细胞。在这两种情况下，L-PEI均诱导报告基因显著且持久（≥15天）表达。最后，尽管全身递送L-PEI/DNA复合物可导致肺中高水平表达，但该方法不适用于转染大腿皮下植入的肿瘤或肺转移瘤。总之，这些结果表明，只要递送方式合适，L-PEI在肿瘤细胞转染方面具有良好特性。
