Chemical Pharmaceutical Research Center, Tasly Academy, Tasly Holding Group Co., Ltd, Tianjin 300410, P. R. China.
J Mater Chem B. 2021 Sep 14;9(34):6895-6901. doi: 10.1039/d1tb00984b. Epub 2021 Aug 16.
Since the nanotoxicity of gene delivery carriers has raised world-wide concerns, it is important to trace their intracellular performance, for example via uptake visualization. Here, we develop a novel ultrathin graphitic carbon nitride (g-CN) composite nanosystem for label-free Raman-traceable small interfering RNA (siRNA) delivery. Through low molecular weight polyethylenimine (PEI) modifications, these nanosystems can obtain siRNA loading capabilities. The lateral size of the PEI-g-CN composite is around 100-150 nm with a thickness of nearly 0.6 nm. The designed label-free delivery system could avoid possible obstacles associated with artificial labels and it shows cytotoxicity toward cancer cells and good biocompatibility in normal human cells. The label-free PEI-g-CN gene nanocarrier can be directly traced via Raman microscopy, which makes it suitable for intracellular visualization. Intracellular uptake of the self-fluorescent g-CN nanosheets can also be traced via fluorescence imaging. The PEI modified g-CN ultrathin nanosheets possess gene delivery capacity together with unique dual-traceable Raman and fluorescence features. Raman traces not only have higher specificity than fluorescence ones but they can also avoid background noises. Thus, they may replace widely implemented fluorescence tracing. This work could provide a label-free traceable platform for investigating the intracellular performances of gene delivery nanosystems.
由于基因传递载体的纳米毒性引起了全世界的关注,因此追踪其细胞内性能非常重要,例如通过摄取可视化。在这里,我们开发了一种新型超薄石墨相氮化碳(g-CN)复合纳米系统,用于无标记拉曼可追踪的小干扰 RNA(siRNA)传递。通过低分子量聚乙烯亚胺(PEI)修饰,这些纳米系统可以获得 siRNA 负载能力。PEI-g-CN 复合材料的横向尺寸约为 100-150nm,厚度接近 0.6nm。设计的无标记传递系统可以避免与人工标记相关的可能障碍,并且对癌细胞表现出细胞毒性,在正常人类细胞中具有良好的生物相容性。无标记的 PEI-g-CN 基因纳米载体可以通过 Raman 显微镜直接追踪,这使其适用于细胞内可视化。自荧光 g-CN 纳米片的细胞内摄取也可以通过荧光成像进行追踪。经过 PEI 修饰的 g-CN 超薄纳米片具有基因传递能力以及独特的双重可追踪拉曼和荧光特性。与荧光相比,拉曼痕迹不仅具有更高的特异性,而且可以避免背景噪音。因此,它们可能取代广泛应用的荧光追踪。这项工作为研究基因传递纳米系统的细胞内性能提供了一个无标记可追踪的平台。