DNA-functionalized Gold Nanorods for Targeted Triple-modal Optical Imaging and Photothermal Therapy of Triple-negative Breast Cancer

Abstract

Targeted imaging and therapy for triple-negative breast cancer (TNBC) in the perioperative period are believed to be imperative for better disease management and improved life expectancy. Still, they are not yet 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 (AuNR), then silica encapsulation. The DNA-based design allows the screening of commercially available positively charged NIR fluorophores for the optimum fluorescence and SERS signals. After the design optimization, we functionalize TMNPs with folate groups to target folate receptor1 (FOLR1)-overexpressing TNBC in vitro and in vivo. Our results reveal that TMNPs preferentially accumulate in the 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 with NIR laser further shows efficient thermal tissue ablation without causing systemic toxicity. Collectively, TMNP holds great promise for real-time multiplexed imaging of cancer biomarkers and therapeutic capability.

CXC Chemokine Receptor Type 4 Antagonistic Gold Nanorods Induce Specific Immune Responses and Long-Term Immune Memory to Combat Triple-Negative Breast Cancer

“…4 Silica-encapsulated DNA-modified AuNRs were employed to PTT of TNBC by targeting folate receptor 1, showing great promise for real-time multiplexed imaging and therapeutic capability. 5 However, there always exist minimal residual lesions in a deeper location with PTT alone, which can cause recurrence and metastasis of the cancers. 6 This problem has attracted great endeavors by combining photothermal agents with immunity inhibitors or immune adjuvants.…”

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

“…Moritz Kircher, unfortunately passed away during the preparation of the manuscript. An older version of this manuscript is available in a pre-print server …”