We demonstrate a MnO2-based nanoreactor to achieve continuous oxygen generation and efficient conversion from glucose to singlet oxygen for combined photodynamic-starvation therapy.

Covalent organic frameworks (COFs) have emerged as promising materials for biomedical applications, but their functions remain to be explored and the potential toxicity concerns should be resolved. Herein, it is presented that carbonization significantly enhances the fluorescence quenching efficiency and aqueous stability of nanoscale COFs. The probes prepared by physisorbing dye-labeled nucleic acid recognition sequences onto the carbonized COF nanoparticles (termed C-COF) were employed for cell imaging, which could effectively light up biomarkers (survivin and TK1 mRNA) in living cells. The C-COF has enhanced photothermal conversion capacity, indicating that the probes are also promising candidates for photothermal therapy. The potential toxicity concern from the aromatic rigid building units of COFs was detoured by carbonization. Overall, carbonization is a promising strategy for developing biocompatible and multifunctional COF-derived nanoprobes for biomedical applications. This work may inspire more versatile COF-derived nanoprobes for bioanalysis and nanomedicine.

A cancer cell membrane-camouflaged nanoreactor was developed for enhanced radiotherapy against cancer metastasis.

Goals: Chemotherapy, the most conventional modality for cancer therapy, usually brings serious side effects because of the low cancer-therapeutic specificity and bioavailability. It is of great significance for cancer treatment to develop new effective strategies to regulate biochemical reactions in organelles, enhance the specificity of chemotherapeutic drugs and reduce their side effects. Methods: We report herein a zeolitic imidazole framework-90 (ZIF-90) based nanoplatform, which was used to initiate a series of mitochondrial cascade reactions using ATP as a molecular switch for cancer therapy. The thioketal linked camptothecin (camptothecin prodrug, TK-CPT) and 2-Methoxyestradiol (2-ME) were encapsulated into the pores of ZIF-90 nanoparticles using a simple one-pot method, and the nanoplatform was finally coated with a layer of homologous cell membrane. Results: Mitochondrial ATP can efficiently degrade ZIF-90 and then release the loaded 2-ME and CPT prodrugs. 2-ME can inhibit the activity of superoxide dismutase (SOD), which induces the up-regulation of reactive oxygen species (ROS) in situ. The thioketal linkers in CPT prodrug can respond to ROS, thereby achieving subsequent release of parent CPT drug. This cascade of reactions can lead to prolonged high oxidative stress and cause continuous cancer cell apoptosis, due to the increased ROS level and the liberation of CPT. Conclusion:We constructed an ATP-triggered strategy using nanoscale ZIF-90 to initiate mitochondrial cascade reactions for cancer therapy. The ZIF-90 based nanoplatform exhibited low cytotoxicity, good mitochondria-targeting ability, and excellent therapeutic effect. In vivo experiments demonstrated that the growth of tumor can be efficiently inhibited in a mouse model. This ATP-triggered strategy to induce mitochondrial biochemical reactions offers more possibilities for developing organelle-targeted therapeutic platforms.

As the most popular nucleic acid probe, molecular beacons (MBs) can selectively light up endogenous RNA targets without specific treatment. However, the poor cell permeability and unsatisfied intracellular stability of MBs significantly restricted their detection performance. Herein, we report the encapsulation of MB within a dual-layered metal–organic framework nanostructure UiO66-ZIF8 for enhanced cell imaging. UiO66-NH2 nanoparticles were synthesized as the template for MB loading, and the ZIF-8 shell was further coated on the surface of UiO66-MB to ensure its stability and lysosomal escape effect. Taking multidrug-resistant (MDR1) mRNA as a model target, MBs loaded within UiO66-ZIF8 showed an improved lysosomal escape effect compared with MB absorbed on UiO66-NH2. Therefore, efficient and accurate intracellular MDR1 mRNA imaging was realized with UiO66-MB-ZIF8. This work presented a new method for the rational regulation of the intracellular fate of MOF-based nanoprobes and will facilitate the further development of hierarchical MOF nanoprobes for analytical applications.