Ce6-DNAzyme-Loaded Metal-Organic Framework Theranostic Agents for Boosting miRNA Imaging-Guided Photodynamic Therapy...

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Oncology

Background:

• Breast cancer is a leading cause of mortality, necessitating advanced theranostic strategies.
• MicroRNA-21 (miR-21) imaging-guided photodynamic therapy (PDT) shows promise but faces challenges in detection sensitivity and therapeutic efficiency.
• Current limitations include low miR-21 abundance due to poor imaging and inefficient PDT.

Purpose of the Study:

• To develop novel theranostic nanoparticles (CDZP NPs) for enhanced breast cancer diagnosis and treatment.
• To integrate dual-cycling signal amplification for sensitive miR-21 detection.
• To improve PDT efficiency by inhibiting reactive oxygen species (ROS) scavenging via GPX4-DNAzyme-mediated gene editing.

Main Methods:

• Synthesized dodecahedral ZIF-8 based nanoparticles encapsulating a dual-cycling miR-21 imaging system and Ce6-DNAzyme therapeutic system.
• Utilized a one-pot synthesis method for creating Ce6-DNAzyme@ZIF-8@PEG nanoparticles (CDZP NPs).
• Evaluated nanoparticle characteristics including biocompatibility, acid-responsive release, and loading capacity. Assessed *in vivo* tumor targeting and therapeutic efficacy in mice.

Main Results:

• CDZP NPs demonstrated excellent biocompatibility, acid-responsive release, and high loading capacity.
• The dual-cycling signal amplification system achieved a low miR-21 detection limit of 3.4 pM.
• Intravenous injection of CDZP NPs effectively targeted tumors, achieving a 72.3% tumor inhibition rate by reducing ROS scavenging and enhancing PDT.

Conclusions:

• The developed CDZP NPs offer a promising theranostic strategy for breast cancer.
• Dual-cycling signal amplification significantly improves miR-21 detection sensitivity.
• GPX4-DNAzyme-mediated inhibition of ROS scavenging enhances PDT efficiency, paving the way for precision breast cancer theranostics.