Gold Nanoparticle-Based Fluorescent Theranostics for Real-Time Image-Guided Assessment of DNA Damage and Repair

Area of Science:

• Nanomedicine
• Molecular Imaging
• Cancer Theranostics

Background:

• Current chemotherapeutic dosing relies on toxicity tolerance.
• Molecular imaging can quantify DNA damage for improved treatment efficacy.
• Apurinic/apyrimidinic (AP)-sites are crucial in DNA repair pathways targeted by chemotherapy.

Purpose of the Study:

• To develop a theranostic tool for real-time monitoring of chemotherapy efficacy.
• To utilize methoxyamine-modified cyanine-7 (Cy7MX) loaded gold nanoparticles (AuNPs) for targeted delivery and imaging of AP-sites.
• To establish a foundation for quantitative assessment of cytotoxic chemotherapies.

Main Methods:

• Conjugation of Cy7MX probe to polyethylene glycol-coated gold nanoparticles (AuNPs).
• Optimization of Cy7MX-AuNP properties using optical spectroscopy.
• In vitro testing of delivery, binding affinity, and release kinetics in DLD1 colon cancer cells.
• In vivo biodistribution and imaging studies in a xenografted mouse model.

Main Results:

• Optimized Cy7MX-AuNPs demonstrated selective and stable intravenous delivery to tumors.
• A 10:1 ratio of Cy7MX-AuNPs showed strong AP site-specific binding.
• High cumulative release (97% in 12 min) of Cy7MX from AuNPs was observed.
• Targeted delivery and accumulation in tumors were confirmed in vivo.

Conclusions:

• Cy7MX-loaded AuNPs represent a promising theranostic platform for cancer treatment.
• This approach enables real-time, quantitative monitoring of chemotherapy efficacy.
• The developed molecular imaging strategy can guide personalized cancer therapy.