DNA-Functionalized Gold Nanorods for Perioperative 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 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 receptor1 (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.

The Emerging Role of Raman Spectroscopy as an Omics Approach for Metabolic Profiling and Biomarker Detection toward Precision Medicine

“…In a more ambitious approach, Pal et al combined photoacoustic, fluorescence, and SERS with DNAfunctionalized gold nanorods with folate moieties to target breast cancer tumors, withIR-780 serving as a multimodal reporter for all three imaging modalities and as a PTT agent (Figure 10d). 242 This highly multifunctional system allowed depth-resolved preoperative imaging with PAI, intraoperative imaging with fluorescence, and postoperative tumor imaging with Raman for comprehensive information gathering. This work is an excellent example that shows that the successful implementation of multimodal nanoprobes is governed by the choice of the nanoparticle for signal enhancement, the choice of imaging modalities that complement each other, and the selection of a reporter that can achieve multiple functionalities.…”

“…(d) DNA-functionalized gold nanorods with folate moieties enable multimodal diagnostics in vivo in murine breast tumors, including photoacoustic imaging for depth-resolved preoperative imaging, fluorescence, and bioluminescence for intraoperative imaging, and Raman spectroscopy for ex vivo postoperative imaging. Adapted with permission from ref . Copyright 2022 American Chemical Society.…”

“…The nanoshells were delivered in vivo subcutaneously and lymphatic trafficking was monitored with PAI with a 680 nm laser wavelength followed by multiplexed biomarker identification in the lymph nodes with a portable Raman. In a more ambitious approach, Pal et al combined photoacoustic, fluorescence, and SERS with DNA-functionalized gold nanorods with folate moieties to target breast cancer tumors, withIR-780 serving as a multimodal reporter for all three imaging modalities and as a PTT agent (Figure d) . This highly multifunctional system allowed depth-resolved preoperative imaging with PAI, intraoperative imaging with fluorescence, and postoperative tumor imaging with Raman for comprehensive information gathering.…”

Losartan-IR820-Loaded Polydopamine Nanoparticles for CO2-Generating Ultrasound Imaging-Guided Photothermal/Photodynamic Therapies of Triple-Negative Breast Cancer

“…Triple-negative breast cancer (TNBC) is an aggressive breast cancer with a low prognosis and high heterogeneity. , Although TNBC is sensitive to chemotherapeutic drugs, the therapeutic effect of adjuvant chemotherapy is decreased because TNBC possesses high interstitial fluid pressure and easy reduction of nicotinamide adenine dinucleotide. , Theranostic nanoparticles (NPs) that integrate therapeutic and imaging functionalities have attracted great attention because they can enhance the intratumoral accumulation of chemotherapeutic drugs, minimize the toxicity of small-molecule drugs toward major organs, and provide high resolution in the bioimaging diagnosis of tumors. − Among them, the theranostic NPs with phototherapy functionality are beneficial to enhance therapeutic effects during the treatment of TNBC in response to minimal invasiveness and low systemic toxicity. − …”

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

“…For examples, the anti-EGFR antibody-conjugated gold nanorods (AuNRs) were applied to NIR-mediated PTT by targeting the epidermal growth factor receptor, showing significant efficacy on the therapy in TNBC . 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 . However, there always exist minimal residual lesions in a deeper location with PTT alone, which can cause recurrence and metastasis of the cancers .…”