Department of Pharmaceutics, School of Pharmaceutical Sciences, Shandong University, 44 West Wenhua Road, Jinan 250012, Shandong, PR China.
J Colloid Interface Sci. 2011 Feb 15;354(2):528-35. doi: 10.1016/j.jcis.2010.10.062. Epub 2010 Nov 3.
The leading principle of non-viral delivery systems for gene therapy is to mediate high levels of gene expression with low cytotoxicity. Nowadays, biodegradable nanoparticles formulated with poly(lactic acid)-poly(ethylene glycol) (PLA-PEG) were wildly developed. However, the relative lower gene transfection efficiency and higher cytotoxicity still remained critical problems. To address these limitations, PLA-PEG nanoparticles have been composited with other components in their formulation. Here, a novel cationic lipid, 6-lauroxyhexyl lysinate (LHLN), was fabricated onto PLA-PEG nanoparticles as a charge modifier to improve the transfection efficiency and cytotoxicity. The obtained cationic LHLN modified PLA-PEG nanoparticles (LHLN-PLA-PEG NPs) could condense pDNA thoroughly via electrostatic force, leading to the formation of the LHLN-PLA-PEG NPs/pDNA complexes (NPs/DNA complexes). The nanoparticles obtained have been characterized in relation to their physicochemical and biological properties, and the results are extremely promising in terms of low cell toxicity and high transfection efficiency. These results indicated that the novel cationic LHLN modified PLA-PEG nanoparticles could enhance gene transfection in vitro and hold the potential to be a promising non-viral nanodevice.
基因治疗的非病毒传递系统的首要原则是用低细胞毒性实现高水平的基因表达。如今，用聚乳酸-聚乙二醇（PLA-PEG）制成的可生物降解纳米粒得到了广泛的开发。然而，相对较低的基因转染效率和较高的细胞毒性仍然是关键问题。为了解决这些局限性，PLA-PEG 纳米粒在其配方中与其他成分复合。在这里，一种新型的阳离子脂质，6-月桂酰氧基己基赖氨酸（LHLN），被制备到 PLA-PEG 纳米粒上作为电荷修饰物，以提高转染效率和细胞毒性。所得的阳离子 LHLN 修饰的 PLA-PEG 纳米粒（LHLN-PLA-PEG NPs）可以通过静电力彻底浓缩 pDNA，形成 LHLN-PLA-PEG NPs/pDNA 复合物（NPs/DNA 复合物）。已对所得纳米粒进行了与理化性质和生物性质有关的特性研究，结果在低细胞毒性和高转染效率方面极具前景。这些结果表明，新型阳离子 LHLN 修饰的 PLA-PEG 纳米粒可以增强体外基因转染，有潜力成为一种有前途的非病毒纳米器件。
