Ultrasound-Mediated Gene Delivery Systems by AG73-Modified Bubble Liposomes
Ultrasound-Mediated Gene Delivery Systems by AG73-Modified Bubble Liposomes
复制标题
DOI：
10.1002/bip.22246
复制
发表时间：
2013-07-01
期刊：
影响因子：
2.9
通讯作者：
Aramaki, Yukihiko
中科院分区：
文献类型：
--
作者：
Negishi, Yoichi;Tsunoda, Yuka;Aramaki, Yukihiko
将靶向基因递送至肿瘤中的新生血管被认为是一种有前途的癌症治疗策略。我们之前报道过“气泡脂质体”（BL）是超声（US）成像气体封装脂质体，适用于超声成像和基因递送。当 BL 暴露于 US 时，气泡被破坏，通过空化产生喷射流，并导致细胞外质粒 DNA (pDNA) 或其他核酸瞬间喷射到细胞质中。我们开发了 AG73 肽修饰的气泡脂质体 (AG73-BL) 作为靶向超声造影剂，其设计用于附着于新生血管肿瘤血管并允许对血管生成进行超声特异性检测 (Negishi 等人, Biomaterials 2013, 34, 501-507)。在本研究中，为了评估 AG73-BL 作为新生血管基因传递工具的有效性，我们检查了 AG73-BL 在美国暴露于原代人内皮细胞 (HUVEC) 中的基因转染效率。与没有肽或乱序肽的 BL 修饰相比，如果将附着在 HUVEC 上的 AG73-BL 暴露于 US，转染效率会显着提高。此外，转染AG73-BL后细胞活力大于80%。这些结果表明，在US暴露破坏AG73-BL后，US暴露可以有效地诱导空化作用，以对抗AG73-BL与HUVEC细胞表面的结合，并且可以增强随后的基因递送到细胞中。因此，AG73-BL 可用于基因递送以及新生血管的超声成像。 (C) 2013 年 Wiley 期刊公司。
Targeted gene delivery to neovascular vessels in tumors is considered a promising strategy for cancer therapy. We previously reported that "Bubble liposomes" (BLs), which are ultrasound (US) imaging gas-encapsulating liposomes, were suitable for US imaging and gene delivery. When BLs are exposed to US, the bubble is destroyed, creating a jet stream by cavitation, and resulting in the instantaneous ejection of extracellular plasmid DNA (pDNA) or other nucleic acids into the cytosol. We developed AG73 peptide-modified Bubble liposomes (AG73-BL) as a targeted US contrast agent, which was designed to attach to neovascular tumor vessels and to allow specific US detection of angiogenesis (Negishi et al., Biomaterials 2013, 34, 501-507). In this study, to evaluate the effectiveness of AG73-BL as a gene delivery tool for neovascular vessels, we examined the gene transfection efficiency of AG73-BLwith US exposure in primary human endothelial cells (HUVEC). The transfection efficiency was significantly enhanced if the AG73-BL attached to the HUVEC was exposed to US compared to the BL-modified with no peptide or scrambled peptide. In addition, the cell viability was greater than 80% after transfection with AG73-BL. These results suggested that after the destruction of the AG73-BLwith US exposure, a cavitation could be effectively induced by the US exposure against AG73-BL binding to the cell surface of the HUVEC, and the subsequent gene delivery into cells could be enhanced. Thus, AG73-BL may be useful for gene delivery as well as for US imaging of neovascular vessels. (C) 2013 Wiley Periodicals, Inc.