Yoshikawa Naoki, Fumoto Shintaro, Yoshikawa Keiko, Hu Die, Okami Kazuya, Kato Riku, Nakashima Mikiro, Miyamoto Hirotaka, Nishida Koyo
Department of Pharmacy, University of Miyazaki Hospital, 5200 Kihara, Kiyotake-cho, Miyazaki 889-1692, Japan.
Graduate School of Biomedical Sciences, Nagasaki University, 1-7-1 Sakamoto, Nagasaki-shi, Nagasaki 852-8501, Japan.
Pharmaceutics. 2020 Apr 10;12(4):341. doi: 10.3390/pharmaceutics12040341.
Understanding the in vivo fate of lipoplex, which is composed of cationic liposomes and DNA, is an important issue toward gene therapy. In disease conditions, the fate of lipoplex might change compared with the normal condition. Here, we examined the contribution of interaction with serum components to in vivo transfection using lipoplex in hepatitis mice. Prior to administration, lipoplex was incubated with serum or albumin. In the liver, the interaction with albumin enhanced gene expression in hepatitis mice, while in the lung, the interaction with serum or albumin enhanced it. In normal mice, the interaction with albumin did not enhance hepatic and pulmonary gene expression. Furthermore, hepatic and pulmonary gene expression levels of albumin-interacted lipoplex were correlated with serum transaminases in hepatitis mice. The albumin interaction increased the hepatic accumulation of lipoplex and serum tumor necrosis factor-α level. We suggest that the interaction with albumin enhanced the inflammation level after the administration of lipoplex in hepatitis mice. Consequently, the enhancement of the inflammation level might enhance the gene expression level. Information obtained in the current study will be valuable toward future clinical application of the lipoplex.
了解由阳离子脂质体和DNA组成的脂质体复合物在体内的命运,是基因治疗的一个重要问题。在疾病状态下,脂质体复合物的命运可能与正常状态相比有所变化。在此,我们研究了在肝炎小鼠中使用脂质体复合物时,与血清成分的相互作用对体内转染的影响。在给药前,将脂质体复合物与血清或白蛋白孵育。在肝脏中,与白蛋白的相互作用增强了肝炎小鼠的基因表达,而在肺中,与血清或白蛋白的相互作用增强了基因表达。在正常小鼠中,与白蛋白的相互作用并未增强肝脏和肺部的基因表达。此外,在肝炎小鼠中,与白蛋白相互作用的脂质体复合物的肝脏和肺部基因表达水平与血清转氨酶相关。白蛋白相互作用增加了脂质体复合物在肝脏中的积累以及血清肿瘤坏死因子-α水平。我们认为,在肝炎小鼠中,与白蛋白的相互作用在脂质体复合物给药后增强了炎症水平。因此,炎症水平的提高可能会增强基因表达水平。本研究中获得的信息对于脂质体复合物未来的临床应用将具有重要价值。