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

• Published in: International journal of molecular sciences Vol. 20; no. 3; p. 471
• Main Authors: Srinivasan, Shriya S, Seenivasan, Rajesh, Condie, Allison, Gerson, Stanton L, Wang, Yanming, Burda, Clemens
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 22-01-2019; MDPI
• Subjects: AP-targeted delivery; Base excision repair; Biomarkers; Blood; Cell Line, Tumor; Cell proliferation; chemotheranostic; Chemotherapy; Cy7MX-loaded gold nanoparticles; Cytotoxic agents; Cytotoxicity; Damage tolerance; Deoxyribonucleic acid; DNA; DNA damage; DNA Damage - physiology; DNA repair; DNA Repair - physiology; DNA repair mechanism; Drug dosages; Fluorescence; Gold; Gold - chemistry; Humans; Metal Nanoparticles - chemistry; molecular probe; Molecular Structure; Nanoparticles; Necrosis; Polyethylene glycol; Precision medicine; real-time imaging; Repair; Schedules; Theranostic Nanomedicine - methods; Tumor cells; Tumors; Cy7MX-loaded gold nanoparticles; AP-targeted delivery; real-time imaging; DNA repair mechanism; chemotheranostic; molecular probe
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms20030471

Chemotherapeutic dosing, is largely based on the tolerance levels of toxicity today. Molecular imaging strategies can be leveraged to quantify DNA cytotoxicity and thereby serve as a theranostic tool to improve the efficacy of treatments. Methoxyamine-modified cyanine-7 (Cy7MX) is a molecular probe which binds to apurinic/apyrimidinic (AP)-sites, inhibiting DNA-repair mechanisms implicated by cytotoxic chemotherapies. Herein, we loaded (Cy7MX) onto polyethylene glycol-coated gold nanoparticles (AuNP) to selectively and stably deliver the molecular probe intravenously to tumors. We optimized the properties of Cy7MX-loaded AuNPs using optical spectroscopy and tested the delivery mechanism and binding affinity using the DLD1 colon cancer cell line in vitro. A 10:1 ratio of Cy7MX-AuNPs demonstrated a strong AP site-specific binding and the cumulative release profile demonstrated 97% release within 12 min from a polar to a nonpolar environment. We further demonstrated targeted delivery using imaging and biodistribution studies in vivo in an xenografted mouse model. This work lays a foundation for the development of real-time molecular imaging techniques that are poised to yield quantitative measures of the efficacy and temporal profile of cytotoxic chemotherapies.