Xie XiangYang, Yang YanFang, Yang Yang, Mei XingGuo
a Beijing Institute of Pharmacology and Toxicology , Beijing , China .
b Wuhan General Hospital of Guangzhou Military Command , Wuhan , China , and.
J Drug Target. 2015;23(9):789-99. doi: 10.3109/1061186X.2015.1009077. Epub 2015 Feb 13.
Light is an ideal general triggered signal, which occurs as a result of its non-invasive nature, desirable controllability and high spatial resolution. However, due to its low penetrability and ability to harm tissues, the use of ultraviolet (UV) light for triggered nanocarrier release in in vivo applications has been limited. Compared with UV light, near-infrared (NIR) light deeply penetrates tissues and is less damaging to cells. In this study, we have devised and tested a strategy for site-specific delivery of small interfering RNA (siRNA) into cancer cells by using liposomes bearing a photolabile-caged peptide (PCP). The positive charges of the lysine residues on the cell-penetrating peptide (CPP) were temporarily caged by the NIR two-photon excitation-responsive protective groups (PG), thereby forming a PCP. Once illuminated by NIR light at tumor tissues, these PGs were cleaved; the positively charged CPP regained its activity and facilitated rapid intracellular delivery of the liposomes into cancer cells. The PCP was connected with 1,2-distearoyl-sn-glycero-3-phosphoethanolamine via a polyethylene glycol (PEG) spacer to prepare the modified liposomes (PCP-LP). Subsequent research demonstrated that the application of the PCP modifications may provide an approach for the selectively targeted delivery of siRNA.
光作为一种通用的触发信号具有诸多优势，因其具有非侵入性、良好的可控性和高空间分辨率。然而，由于其穿透性低且可能对组织造成损伤，紫外线（UV）光在体内应用中用于触发纳米载体释放受到限制。与紫外线相比，近红外（NIR）光能够深入穿透组织且对细胞损伤较小。在本研究中，我们设计并测试了一种策略，即通过使用带有光不稳定笼状肽（PCP）的脂质体将小干扰RNA（siRNA）位点特异性递送至癌细胞。细胞穿透肽（CPP）上赖氨酸残基的正电荷被近红外双光子激发响应保护基团（PG）暂时笼蔽，从而形成PCP。一旦在肿瘤组织处用近红外光照射，这些PG就会被裂解；带正电荷的CPP恢复其活性，并促进脂质体快速向癌细胞内递送。PCP通过聚乙二醇（PEG）间隔物与1,2-二硬脂酰-sn-甘油-3-磷酸乙醇胺相连，以制备修饰脂质体（PCP-LP）。后续研究表明，PCP修饰的应用可能为siRNA的选择性靶向递送提供一种方法。
