ArticleACS nano2024
Autonomous Feedback-Driven Engineered DNAzyme-Coated Trojan Horse-like Nanocapsules for On-Demand CRISPR/Cas9 Delivery.
Article in ACS nano, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed.
- PANDA: AND logic-gated RNA sensing enabled by a photo-activated RCA-Argonaute cascade.Chemical science · 2026Article
- DNAzyme-Based Nanostructures for Dynamic Cell Regulation and Sensing.ChemistryOpen · 2026Review
- Advances in DNAzyme Selection, Molecular Engineering and Biomedical Applications.International journal of molecular sciences · 2026Review
- Spatiotemporally delivery of Cas9 ribonucleoprotein/DNAzyme logic systems using near-infrared upconversion nanomachine for precise immunotherapy.Acta pharmaceutica Sinica. B · 2025Article
- Non-Invasive Delivery of CRISPR/Cas9 Ribonucleoproteins (Cas9 RNPs) into Cells via Nanoparticles for Membrane Transport.Pharmaceutics · 2025Review
- Smart Nanoarchitectures for Precision RNA Delivery: Harnessing Endogenous and Exogenous Stimuli in Cancer Treatment.Theranostics · 2025Review
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Authors and funding
11 authors.
Funding
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Abstract
Manipulating the expression of cellular genes through efficient CRISPR/Cas9 delivery is rapidly evolving into a desirable tumor therapeutics. The exposure of CRISPR/Cas9 to a complex external environment poses challenges for conventional delivery carriers in achieving responsive and accurate release. Here, we report a Trojan horse-like nanocapsule for the on-demand delivery of CRISPR/Cas9 in a microRNA-responsive manner, enabling precise tumor therapy. The nanocapsule comprises a nanoassembled, engineered DNAzyme shell encasing a Cas9/sgRNA complex core. The DNAzyme, functioning as a catalytic unit, undergoes a conformational change in the presence of tumor-associated microRNA, followed by activating a positive feedback-driven autonomous catabolic cycle of the nanocapsule shell. This catabolic cycle is accomplished through chain reactions of DNAzyme "cleavage-hybridization-cleavage", which ensures sensitivity in microRNA recognition and effective release of Cas9/sgRNA. Utilizing this Trojan horse-like nanocapsule, as low as 1.7 pM microRNA-21 can trigger the on-demand release of Cas9/sgRNA, enabling the specific editing of the protumorigenic microRNA coding gene. The resulting upregulation of tumor suppressor genes induces apoptosis in tumor cells, leading to significant inhibition of tumor growth by up to 75.94%. The Trojan horse-like nanocapsule, with superior programmability and biocompatibility, is anticipated to serve as a promising carrier for tailoring responsive gene editing systems, achieving enhanced antitumor specificity and efficacy.
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