A Layered-Responsive DNA Tetrahedral Nanomachine for Precise Cancer Cell Imaging and Selective cGAS-STING Signaling...

Area of Science:

• Biotechnology
• Nanotechnology
• Molecular Biology

Background:

• Accurate cancer cell imaging and selective immune pathway activation are critical challenges.
• DNA nanomachines offer potential for targeted recognition and multi-stimulus responses.

Purpose of the Study:

• To develop a dual tetrahedral DNA nanomachine (DTDN) for cancer cell imaging and cGAS-STING pathway activation.
• To achieve precise targeting and controlled immune response using a DNA nanomachine.

Main Methods:

• AS1411 aptamer modification for cancer cell targeting and internalization.
• Cascaded AND logic gate with reconfigurable DNA modules for sequential activation.
• Hybridization chain reaction (HCR) for amplified fluorescence signal generation.
• Utilized apurinic/apyrimidinic endonuclease 1 (APE1) and miR-21 as triggers.

Main Results:

• DTDN achieved selective cancer cell targeting and internalization.
• Sequential activation released functional hairpins and initiated HCR, generating fluorescent dsDNA.
• Generated dsDNA activated the cGAS-STING pathway, enabling cancer cell imaging and immune signaling.
• Dual-locked cascade strategy demonstrated high specificity and anti-interference capabilities.

Conclusions:

• The developed DTDN is a programmable, safe, and reliable nucleic acid nanoplatform.
• This platform enables precise cancer diagnosis through amplified fluorescence imaging.
• It facilitates cGAS-STING pathway-based regulatory therapy for cancer treatment.