Many Birds, One Stone: A Smart Nanodevice for Ratiometric Dual-Spectrum Assay of Intracellular MicroRNA and Multimodal Synergetic Cancer Therapy

Abstract

The development of a theragnostic platform integrating precise diagnosis and effective treatment is significant but still extremely challenging. Herein, an integrated smart nanodevice composed of Au@Cu2–x S@polydopamine nanoparticles (ACSPs) and fuel DNA-conjugated tetrahedral DNA nanostructures (fTDNs) was constructed, in which the ACSP nanoprobe played multiple key roles in antitumor therapy as well as in situ monitoring of microRNAs (miRNAs) in cancer cells. Regarding the analysis, the ACSP probe contained two optical properties: excellent surface-enhanced Raman scattering (SERS) enhancement and high fluorescence (FL) quenching performance. Employing the ACSPs as the high-efficiency detection substrate combined with the fTDN-assisted DNA walking nanomachines as the superior amplification strategy, a SERS-FL dual-spectrum biosensor was constructed, which achieved an ultralow background signal and excellent sensitivity with detection limits of 0.11 pM and 4.95 aM by FL and SERS, respectively. Moreover, the rapid FL imaging and precise SERS quantitative detection for miRNA in cancer cells were also achieved by dual-signal ratio strategy, improving the accuracy of diagnosis. Regarding the therapeutic application, due to the high reactive oxygen species generation ability and excellent photothermal conversion efficiency, the ACSPs can also act as an all-in-one nanoagent for multimodal collaborative tumor therapy. Significantly, both in vivo and in vitro experiments confirmed its high biological safety and strong anticancer effect, indicating its promising theragnostic applications.

Signal Transduction Strategies for Analyte Detection Using DNA‐Based Nanostructures

“…[78,79] Equally important will be the incorporation of amplification elements to enable the detection of low-abundance targets. Recent developments in signal amplification using DNA nanostructures include strategies such as enzyme-based amplification, [5] hybridization chain reaction, [13,23] hairpin DNA cascade amplification, [80] DNA walking amplification, [56] and entropy-driven tetrahedral DNA amplification. [66,72] In addition, the creation of integrated systems that detect analytes in a minimal number of steps is highly desirable.…”

Emerging Nanotheranostics for 5-Fluorouracil in Cancer Therapy: A Systematic Review on Efficacy, Safety, and Diagnostic Capability

“…Plasmonic gold NTA-mediated photothermal therapy has also been tested in combination with chemotherapy and immunotherapy to achieve synergistic tumor inhibition in the 4T1 tumor model ( Zhang et al, 2020 ; Chen et al, 2021 ). On the other hand, plasmonic NTA also possesses the ability to utilize light energy to generate reactive oxygen species (photodynamic therapy) for the destruction of tumors ( He et al, 2021b ; Chen et al, 2021 ; Shanmugam et al, 2021 ). In addition, plasmonic NTA enables real-time visualization of the tumor and precise tracking of NTA in the tumors via photoacoustic imaging to facilitate image-guided treatment ( He et al, 2021a ; Shan et al, 2021 ; Shanmugam et al, 2021 ; Zhu et al, 2022 ).…”

SERS Tags for Biomedical Detection and Bioimaging

“…Owing to their enzyme-free and isothermal DNA reaction characteristics, strategies of catalytic hairpin assembly (CHA) amplification and hybridization chain reaction (HCR) have also been integrated with SERS tags for miRNAs detection 97 - 100 . The process of CHA amplification is as follows: miRNA target first triggers the hybridization of hairpin structured H1 and H2.…”

“…Furthermore, SERS-guided multimodal therapeutic strategies have also been presented by other groups 97 , 198 , 199 . For instance, Lee's group reported a hybrid graphene oxide/gold nanoparticle-based cancer-specific nuclei acid conjugate (Au@GO NP-NACs) for multimodal imaging and combined therapeutics of cancer cells.…”

“…This C-GERTs nanoprobe can effectively control the spread of disseminated tumors in mice and could serve as a safe and powerful tool for the treatment of advanced ovarian cancers. Very recently, He et al demonstrated an integrated smart nanodevice, composed of Au@Cu 2-x S@polydopamine nanoparticles (ACSPs) and fuel DNA-conjugated tetrahedral DNA nanostructures (fTDNs), as one stone for many birds ( Figure 11 C) 97 . Regarding the analysis, the ACSP probe contained two optical properties: SERS enhancement and fluorescence quenching performance.…”