Aptamer-DNAzyme Metal-Nucleic Acid Frameworks Show Promise for Targeted Gastric Cancer Therapy

Recent research demonstrates that aptamer-DNAzyme-based metal-nucleic acid frameworks (MNFs) represent a significant advancement in targeted gastric cancer therapy, offering improved stability, synthesis efficiency, and tumor specificity compared to earlier nanomaterial approaches.

Aptamer-DNAzyme MNFs are engineered by integrating long oligonucleotide sequences with metal ions, resulting in frameworks that are more stable and easier to synthesize under mild conditions. The use of longer DNA sequences enhances folding and entanglement, which not only stabilizes the MNFs but also allows for efficient drug loading and targeted delivery. The incorporation of aptamer tails provides precise recognition of cancer biomarkers (e.g., HER2), enabling selective targeting of gastric cancer cells. DNAzyme components within the framework facilitate gene regulation, such as silencing oncogenic mRNA or microRNA, leading to energy depletion and cancer cell death.

These MNFs can be synthesized at room temperature and do not require additional carriers, simplifying their delivery. In preclinical models, aptamer-DNAzyme MNFs loaded with therapeutic proteins or imaging agents demonstrated effective targeting and cytotoxicity against HER2-positive gastric cancer cells, as well as dual gene regulation for enhanced anti-tumor effects. This approach addresses previous limitations of instability, harsh synthesis conditions, and lack of tumor specificity.

Aptamer-DNAzyme-based metal-nucleic acid frameworks offer a promising, targeted, and efficient strategy for gastric cancer therapy, overcoming key barriers of previous nanomaterial systems and showing strong preclinical efficacy. Further research is needed to confirm safety and effectiveness in clinical settings.

Reference：

https://pubmed.ncbi.nlm.nih.gov/38693181/