Biological Logic-Gated DNA Self-Assembly Strategy for Precision Tumor Imaging and Selective Activation of the...

Area of Science:

• Biotechnology
• Immunology
• Nanomedicine

Background:

• The cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway is a key target for cancer immunotherapy.
• Conventional synthetic nucleic acids can cause off-target effects and systemic inflammation, hindering clinical use.

Purpose of the Study:

• To develop a programmable DNA nanosystem for tumor-restricted cGAS-STING activation.
• To create an intelligent immunotherapy platform integrating immune modulation and diagnostic feedback.

Main Methods:

• Designed a programmable DNA nanosystem (MP-DNA) with AND-gate logic responding to apurinic/apyrimidinic endonuclease 1 (APE1) and microRNA-10b.
• Utilized hybridization chain reaction (HCR) to generate immunostimulatory double-stranded DNA (dsDNA) polymers.
• Incorporated MnO2 nanosponges (MnO2 NSs) for drug delivery and synergistic STING activation.

Main Results:

• MP-DNA achieved tumor-specific cGAS-STING activation based on dual biomarker detection.
• Generated dsDNA polymers acted as immunostimulants and fluorescent reporters for real-time imaging.
• Localized immune activation increased lymphocyte infiltration into tumors, and Mn2+ release enhanced STING activation.

Conclusions:

• The developed MP-DNA nanosystem offers a programmable and intelligent platform for cancer immunotherapy.
• This approach enables precise immune modulation and diagnostic feedback, improving antitumor efficacy while minimizing toxicity.
• The study provides a framework for designing advanced nucleic acid therapeutics for cancer treatment.