DNA-Functionalized Gold Nanorods for Perioperative Optical Imaging and Photothermal Therapy of Triple-Negative Breast Cancer

Targeted imaging and therapy for triple-negative breast cancer (TNBC) in the perioperative period are imperative for better disease management and improved life expectancy. Still, they are not available in clinical settings, and only a few nanoparticle-based theranostic agents potentially offer these capabilities. Herein, we develop an innovative class of biocompatible triple-modality nanoprobes (TMNPs) that offer optical imaging using optoacoustic, fluorescence, and surface-enhanced Raman scattering (SERS), as well as photothermal therapy (PTT) with near-infrared (NIR) light. The TMNPs are fabricated by immobilizing positively charged NIR fluorophores on negatively charged DNA-coated gold nanorods (AuNRs), followed by silica encapsulation. The DNA-based design allows the screening of commercially available positively charged NIR fluorophores for the optimum fluorescence emission and SERS. After design optimization, we functionalize TMNPs with folate groups to target folate receptorl (FOLR1)-overexpressing TNBC in vitro and in vivo. Our results reveal that TMNPs preferentially accumulate in FOLR1 positive tumors in TNBC patient-derived xenograft mouse models and show excellent imaging capabilities with all three imaging modalities. Selective exposure of the tumor to a NIR laser shows efficient thermal tissue ablation without causing systemic toxicity. Collectively, TMNPs hold great promise for real-time multiplexed imaging of cancer biomarkers and therapeutic capability.