Endo/lysosomal escape and gene release are two critical bottlenecks in gene delivery. Herein, a novel photo-controllable metal-organic frameworks (MOFs) nanoswitch is rationally designed for enhancing small interfering RNA (siRNA) delivery. One single laser triggers the “off-to-on” switching of MOFs nanocomplexes, inducing significant siRNA release accompanied by rapid MOFs dissociation into protonatable 2-methylimidazalo and osmotic rupturing Zn²⁺ ions, which cooperatively contribute to remarkable endo/lysosomal rupture (∼ 90%). The simultaneous endo/lysosomal rupture and release enable a high spatio-temporal control on RNA interference for effective cancer therapy. Notably, the “off-to-on” switching also activates fluorescence recovery for real-time monitoring siRNA delivery. The nanoswitch could easily be extended to deliver other therapeutic agents (e.g., DNA, protein, anticancer drug) for overcoming endo/lysosomal entrapment.

中文翻译：

---

金属有机框架纳米开关：朝着光可控的内/溶酶体破裂和释放，以增强癌症RNA的干扰

内吞/溶酶体逃逸和基因释放是基因传递中的两个关键瓶颈。本文中，合理地设计了新颖的光可控金属-有机框架（MOF）纳米开关，以增强小干扰RNA（siRNA）的传递。单个激光触发MOF纳米复合物的“从开到关”切换，诱导大量siRNA释放，伴随MOF迅速分解成质子化的2-甲基咪唑并渗透破坏Zn ²⁺离子，共同导致显着的内/溶酶体破裂（约90％）。同时的内/溶酶体破裂和释放使得能够对RNA干扰进行高度的时空控制，以进行有效的癌症治疗。值得注意的是，“ on-to-on”开关还可以激活荧光恢复，以实时监测siRNA的传递。纳米开关可以容易地扩展以递送其他治疗剂（例如，DNA，蛋白质，抗癌药）以克服内吞/溶酶体的包裹。