Wang Bing, Zhang Ji, Liu Yan-Hong, Zhang Wei, Xiao Ya-Ping, Zhao Rui-Mo, Yu Xiao-Qi
Key Laboratory of Green Chemistry and Technology (Ministry of Education), College of Chemistry, Sichuan University, Chengdu 610064, P. R. China.
J Mater Chem B. 2018 May 14;6(18):2860-2868. doi: 10.1039/c8tb00392k. Epub 2018 Apr 24.
In the past few decades, although various reduction-responsive nanocarriers have been designed and explored for gene delivery, it is difficult to directly detect or monitor the reduction capability of these carriers, especially under intracellular conditions. Taking advantage of the generated fluorescence signal in the reduction process of the naphthalimide-sulfonamide (NS) group, we developed a novel liposomal nanocarrier, FNSL, which showed reduction-sensitive property and self-reporting character. As a new reduction-responsive site in a gene delivery system, the NS group in FNSL is capable of responding to glutathione (GSH) and simultaneously emitting green fluorescence at 500 nm in both extra- and intracellular circumstances. Hence, it will be very convenient to assess the reducibility of this carrier and monitor the stimuli-responsive gene release via fluorescence signal. FNSL has high affinity for DNA and can condense it into nanoparticles with a proper nano-size and zeta potential. Compared with the non-reducible FNAL, FNSL showed enhanced gene release capability, higher transfection efficiency (TE), and lower cytotoxicity. Furthermore, treatment of FNSL-mediated transfection with slightly exogenous GSH greatly improved the TE of FNSL in HepG2 cells, and its TE was even higher than that of Lipofectamine 2000. These results demonstrate that FNSL possesses great potential for efficient and low-toxicity gene delivery, and this study on a bioreducible liposome with self-reporting ability would be a guide for further research on the development of biodegradable gene carriers.
在过去几十年中，尽管已经设计并探索了各种还原响应型纳米载体用于基因递送，但很难直接检测或监测这些载体的还原能力，尤其是在细胞内条件下。利用萘二甲酰亚胺 - 磺酰胺（NS）基团还原过程中产生的荧光信号，我们开发了一种新型脂质体纳米载体FNSL，它具有还原敏感性和自报告特性。作为基因递送系统中的一个新的还原响应位点，FNSL中的NS基团能够对谷胱甘肽（GSH）作出反应，并在细胞外和细胞内环境中同时在500 nm处发出绿色荧光。因此，通过荧光信号评估该载体的还原性并监测刺激响应型基因释放将非常方便。FNSL对DNA具有高亲和力，并且可以将其浓缩成具有合适纳米尺寸和zeta电位的纳米颗粒。与不可还原的FNAL相比，FNSL表现出增强的基因释放能力、更高的转染效率（TE）和更低的细胞毒性。此外，用少量外源性GSH处理FNSL介导的转染大大提高了FNSL在HepG2细胞中的TE，其TE甚至高于Lipofectamine 2000。这些结果表明FNSL在高效低毒基因递送方面具有巨大潜力，并且这项关于具有自报告能力的生物可还原脂质体的研究将为可生物降解基因载体的进一步开发研究提供指导。
