Super-assembled silica nanoprobes for intracellular Zn(II) sensing and reperfusion injury treatment through MOF crystallization.

The production of excess free zinc ions (Zn) in cells has been identified as an important cause of cell injury or apoptosis after ischemia reperfusion. Thus, developing a nanosystem with multiple therapeutic functions to significantly eliminate multiple cell injury factors is of great interest. Here, a super-assembled nanosystem consisting of a polyethylene glycol (PEG) surface-modified mesoporous silica nanoparticle (MSN) encapsulating 2-methylimidazole (2MI) and a Zn probe (PZn) was fabricated. The 2MI-P@MSN nanoassemblies showed a "turn-on" fluorescence signal at 476 nm toward zinc ions due to the presence of PZn. Besides, zeolitic imidazolate framework-8 (ZIF-8) could be assembled on the site intracellularly after 2MI chelating with free zinc ions. The experimental results revealed that 2MI-P@MSN exhibited excellent biocompatibility and non-cytotoxicity, and was able to provide satisfactory protection to OGD/R-treated cells based on zinc ion adsorption and the antioxidant effect of ZIF-8, which could effectively improve the survival rate of reperfusion injury cells from 52% to 73%. Notably, selective and quantitative sensing of Zn was successfully carried out in the cells. This strategy highlights the potential of the detection, absorption and assembly of excess zinc ions simultaneously for cell therapy, which provides a promising therapeutic method for ischemic stroke, oxidative damage and diseases associated with zinc ion accumulation.