Glutathione-Responsive Heterogeneous Metal-Organic Framework Hybrids for Photodynamic-Gene Synergetic Cell Apoptosis

Chemistry. 2022 Mar 20. doi: 10.1002/chem.202200305. Online ahead of print.ABSTRACTIntracellular excessive glutathione (GSH) consumes the cytotoxic 1 O 2 significantly, restricting the development and efficacy of 1 O 2 -mediated photodynamic therapy (PDT). To face with this challenge, herein a heterogeneous metal-organic framework (MOF) nanohybrid was sequentially fabricated with porous coordination network-typed MOF as the core and photosensitizer, and Cu II -centered zeolitic imidazolate framework-67 as shell encapsulating cyanine 3-labelled siRNA. Upon internalized by cells and activated by GSH, the outer shell dissociated and released dye-labelled siRNA for GSH imaging and subsequent gene silencing in a controllable way. Meanwhile, the photosensitizing core was synchronously unlocked for the GSH-depleted intensified PDT along with the dissociation. The heterogeneous nanosystem achieved efficiently imaging-guided photodynamic-gene theranostics with the cell apoptosis of 81.3%, which was 2.2 folded than that without PDT. Overall, the core-shell heterogeneous MOF hybrids exerted effective photodynamic-gene synergetic therapeutic efficacy by surmounting GSH-associated resistance, and paved a new way for designing intracellular stimulus-activated theranostic strategies.PMID:35307887 | DOI:10.1002/chem.202200305
Source: Chemistry - Category: Chemistry Authors: Source Type: research