Functional Zeolitic Imidazolate Framework for Robust l-Deoxyribozyme-Based Therapy

Programmable chiral biocatalysis represents a promising therapeutic strategy for its high stereospecific control over various biotransformations (e.g., chiral A beta isomerization) of living entities yet is rarely explored. With an extraordinary resistance to nuclease digestion, the non-natural left-handed deoxyribozyme (l-DNAzyme) therapy is constrained by inefficient delivery/release and insufficient cofactors supply. Herein, an efficient adenosine triphosphate (ATP)-stimulated disassembly of l-histidine (l-His)-integrated ZIF-8 (l-His-ZIF-8) is reported for sustaining the l-DNAzyme-amplified photodynamic therapy. This self-sufficient l-therapeutic platform can intelligently release the l-DNAzyme probe and simultaneously supply l-His DNAzyme cofactors via endogenous ATP. Then, the intrinsic microRNA-21 catalyzes the generation of robust l-DNAzyme via the catalytic hybridization reaction for activating the photosensitizer with multiplied guaranteed therapeutic operation. This l-therapeutic strategy opens up great prospects for more precise diagnosis and customized gene silencing-based therapy.

Automated summary

Programmable chiral biocatalysis is a promising therapeutic strategy for precise control over biotransformation processes. This study reports an efficient ATP-stimulated disassembly method to sustain l-DNAzyme-amplified photodynamic therapy. The self-sufficient l-therapeutic platform can intelligently release l-DNAzyme probe and supply l-His DNAzyme cofactors via endogenous ATP.