Multifunctional DNA nanoprobe for tumor-targeted synergistic therapy by integrating chemodynamic therapy with gene...

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Molecular Biology

Background:

• Tumor complexity necessitates multi-mode synergistic therapies for improved efficacy.
• Multifunctional probes are essential for realizing synergistic therapeutic strategies.
• DNA nanotechnology offers a versatile platform for designing advanced therapeutic agents.

Purpose of the Study:

• To design and develop a multifunctional DNA tetrahedron nanoprobe for synergistic cancer therapy.
• To integrate chemodynamic therapy (CDT) and gene silencing into a single nanoplatform.
• To evaluate the targeted antitumor efficacy and specificity of the developed nanoprobe.

Main Methods:

• Fabrication of a DNA tetrahedron nanoprobe integrating silver nanoclusters (as CDT reagent) and antagomir-21 (as gene silencing agent).
• Incorporation of an aptamer for targeted recognition and delivery into cancer cells.
• In vitro evaluation of the nanoprobe's ability to silence miRNA-21 and generate hydroxyl radicals (˙OH) in cancer cells.
• Assessment of the cytotoxic effects on HeLa cancer cells and normal cells.

Main Results:

• The DNA tetrahedron nanoprobe (D-sgc8-DTNS-AgNCs-Anta-21) successfully entered cancer cells and performed dual functions.
• Effective silencing of endogenous miRNA-21 and generation of toxic ˙OH via reaction with H₂O₂ were observed.
• Concentration-dependent apoptosis was induced in HeLa cancer cells.
• Normal cells exhibited minimal impact, demonstrating high specificity and biocompatibility.

Conclusions:

• The multifunctional DNA tetrahedron nanoprobe provides a promising strategy for synergistic antitumor therapy.
• DNA nanotechnology enables the assembly of complex probes with diverse functionalities for targeted cancer treatment.
• The developed platform highlights the potential of combining CDT and gene silencing for enhanced therapeutic outcomes with reduced side effects.