Negishi Yoichi, Tsunoda Yuka, Endo-Takahashi Yoko, Oda Yusuke, Suzuki Ryo, Maruyama Kazuo, Yamamoto Matsuo, Aramaki Yukihiko
Department of Drug and Gene Delivery Systems, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan.
J Drug Deliv. 2011;2011:203986. doi: 10.1155/2011/203986. Epub 2011 Apr 28.
Recently, we have developed novel polyethylene glycol modified liposomes (bubble liposomes; BL) entrapping an ultrasound (US) imaging gas, which can work as a gene delivery tool with US exposure. In this study, we investigated the usefulness of US-mediated gene transfer systems with BL into synoviocytes in vitro and joint synovium in vivo. Highly efficient gene transfer could be achieved in the cultured primary synoviocytes transfected with the combination of BL and US exposure, compared to treatment with plasmid DNA (pDNA) alone, pDNA plus BL, or pDNA plus US. When BL was injected into the knee joints of mice, and US exposure was applied transcutaneously to the injection site, highly efficient gene expression could be observed in the knee joint transfected with the combination of BL and US exposure, compared to treatment with pDNA alone, pDNA plus BL, or pDNA plus US. The localized and prolonged gene expression was also shown by an in vivo luciferase imaging system. Thus, this local gene delivery system into joint synovium using the combination of BL and US exposure may be an effective means for gene therapy in joint disorders.
最近，我们开发了一种新型聚乙二醇修饰脂质体（气泡脂质体；BL），其包裹着超声（US）成像气体，在超声照射下可作为基因递送工具。在本研究中，我们研究了利用BL介导的基因转移系统在体外对滑膜细胞以及在体内对关节滑膜进行基因转移的有效性。与单独使用质粒DNA（pDNA）、pDNA加BL或pDNA加US处理相比，在经BL和US照射联合处理的原代培养滑膜细胞中可实现高效基因转移。当将BL注射到小鼠膝关节中，并经皮对注射部位进行US照射时，与单独使用pDNA、pDNA加BL或pDNA加US处理相比，在经BL和US照射联合处理的膝关节中可观察到高效的基因表达。体内荧光素酶成像系统也显示了基因的局部和持续表达。因此，这种利用BL和US照射联合的向关节滑膜局部递送基因的系统可能是治疗关节疾病的一种有效基因治疗手段。
