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Dual-Cascade Activated DNAzyme Nanoreactor within a Zn-Based MOF for Mitochondrial Gene Regulation
Xiuyan Wan1, Yukun Tao1, Yingli Ge1
1College of Chemistry, Chemical Engineering and Materials Science, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Institute of Molecular and Nano Science, Shandong Normal University, Jinan 250014, P. R. China.
This study introduces a novel nanoreactor for hepatocellular carcinoma (HCC) gene therapy. The ZIF-90 nanoreactor precisely targets cancer cell mitochondria, delivering DNAzyme for effective gene silencing and tumor suppression.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Cancer Therapy
Background:
- Hepatocellular carcinoma (HCC) gene therapy requires precise targeting.
- Metal-organic frameworks (MOFs) and DNAzymes offer potential for targeted gene delivery.
- Organelle-specific targeting is crucial for effective cancer treatment.
Purpose of the Study:
- To develop a dual-cascade DNAzyme nanoreactor for HCC therapy.
- To achieve precise targeting of HCC cells and their mitochondria.
- To enable organelle-level gene silencing via mRNA cleavage.
Main Methods:
- Construction of a ZIF-90 based nanoreactor.
- Functionalization with lignin, N-acetylgalactosamine, and triphenylphosphonium ligands for cascade targeting.
- Encapsulation of an EGR-1-targeting DNAzyme and Zn2+ cofactors.
- Stimuli-responsive disassembly in the mitochondrial microenvironment.
Main Results:
- The nanoreactor demonstrated programmed disassembly and release of DNAzyme and Zn2+.
- Efficient mitochondrial localization and selective mRNA cleavage were observed.
- In vivo studies showed significant tumor suppression with low toxicity.
Conclusions:
- ZIF-90 nanoreactors offer a promising platform for organelle-specific gene therapy in HCC.
- This approach enables precise gene silencing at the mitochondrial level.
- The combination of MOFs and DNAzymes presents a new strategy for cancer intervention.
