Target-Triggered Nanomaterial Self-Assembly Induced Electromagnetic Hot-Spot Generation for SERS–Fluorescence Dual-Mode In Situ Monitoring MiRNA-Guided Phototherapy

Abstract

A multifunctional theranostic nanosystem that integrates dynamic monitoring and therapeutic functions is necessary for precision tumor medicine. Herein, an entropy-driven self-assembly nanomachine is developed that overcomes the mechanism differences of different diagnostic modes and is applied to miRNA surface-enhanced Raman scattering (SERS)−fluorescence dual-mode dynamic monitoring and synergy phototherapy. It is worth noting that the activated dual-mode theranostic nanosystem (DTN) is capable of tumor in situ fluorescence imaging and SERS absolute quantification of the target. After being internalized into tumor cells, the DTN nanosystem is activated by the DNA cascade chain displacement of the target miR-21, resulting in the secondary release of fluorophores and the assembly of core−satellite structures (CS structures). The coupling of localized surface plasmon resonances (LSPRs) in the CS structure results in the formation of numerous enhanced electric fields (hot spot) in the nanogap of the CS structure. Then the DTN nanosystem greatly improves the sensitivity and repeatability of Raman detection by converting trace targets into numerous adenines residing in the electromagnetic hot spot of the CS structure. Meanwhile, the CS structure and the loaded photosensitizer are used for synergy phototherapy under the guidance of fluorescence imaging. This proposed strategy is confirmed by in vivo and in vitro results, and it provides new ideas for tumor SERS−fluorescence dual-mode diagnosis and effective tumor therapy.

Intracellular miRNA-Triggered Surface-Enhanced Raman Scattering Imaging and Dual Gene-Silencing Therapy of Cancer Cell

“…13,14 How to effectively trigger the assembly of nanoparticle with rich hotspots in live cells by endogenous miRNAs so as to achieve highly sensitive SERS imaging is significantly important but is still a big challenge. 15 Currently, the main approaches adopted to intracellularly assemble nanoparticles are the direct formation of a "nanoparticle-miRNA-nanoparticle" sandwichstructured complex 16,17 or the uncontrollable formation of aggregates due to the change of surface charges on the nanoparticles after the interaction with the miRNAs. 18 The former has a limited number of hot spots due to the extremely low abundance of intercellular miRNAs and the formation of simple sandwich structures, 19,20 while the latter is susceptible to an inhomogeneous SERS signal and even false results due to the uncontrollable and nonspecific aggregation caused by the complex intracellular environment.…”

“…In contrast to the fluorescence imaging which is easily suffering from photobleaching and the interference of biological background, SERS can offer a unique “signature” spectrum profile of molecule with good photostability and can ultrasensitively and specifically detect biomolecules from complex biological environments . SERS is derived from the localized electromagnetic field enhancement around plasmonic nanomaterials, and extremely enhanced Raman signal can be obtained from the nanogaps (i.e., SERS hot spots) between the neighboring plasmonic nanoparticles (NPs). , How to effectively trigger the assembly of nanoparticle with rich hotspots in live cells by endogenous miRNAs so as to achieve highly sensitive SERS imaging is significantly important but is still a big challenge . Currently, the main approaches adopted to intracellularly assemble nanoparticles are the direct formation of a “nanoparticle-miRNA-nanoparticle” sandwich-structured complex , or the uncontrollable formation of aggregates due to the change of surface charges on the nanoparticles after the interaction with the miRNAs .…”

Quantitative and Noninvasive Detection of SAH-Related MiRNA in Cerebrospinal Fluids In Vivo Using SERS Sensors Based on Acupuncture-Based Technology

“…Thus, the concentration of target miR-21-5p can be quantified by the SERS signal intensity relying on the Raman reporter on hpDNA2. Additionally, we applied acupuncture-based technology to verify the nondestructive nature of this detection strategy for cells and achieved long-term in vivo monitoring of miR-21-5p in rat models, which is different from other studies and advantageous. − The results of our search for SERS and miR-21 are listed in Table S1. Therefore, this task proposed a novel strategy by combining hpDNA-conjugated GNSs SERS probes with acupuncture-based technology for noninvasive and quantitative monitoring of miR-21-5p in single cells and rat models, which can offer a promising role in the diagnosis and prognostic judgment of SAH as well as in other relevant clinical applications such as disease diagnosis and monitoring technology.…”

Au Nanoparticles on Superhydrophobic Scaffolds for Large-Area Surface-Enhanced Raman Scattering Substrates

“…Surface-enhanced Raman scattering (SERS) spectroscopy emerged as an extremely powerful analytical technique for obtaining non-invasive, label-free chemical data regarding multiple (bio-)­chemical analytes, owing to its high sensitivity and molecular selectivity, − in addition to unequivocal detection without quenching issues. − Label-free SERS, in particular, enables the identification of the specific spectral fingerprints of probe analytes mounted on a plasmonic substrate (i.e., noble metal nanostructures), wherein SERS exploits the excitations of localized modes of the surface plasmon polaritons of the nanostructured plasmonic substrate. − Thus, field enhancement with the aid of “hot spots” is critical in Raman scattering, transforming SERS spectroscopy to an extremely effective analytical tool owing to its almost single-molecule sensitivity. , SERS detection is thus applied in various fields, such as chemical analysis, medical diagnostics, food safety, , and environmental monitoring. , Additionally, high-throughput screening assay using SERS exhibits the advantages of rapid optical throughput and high quality, while requiring a small amount of the sample . Therefore, the varied possibilities of this versatile, ultrasensitive platform inspired the development of a wide variety of novel plasmonic substrates for use in SERS.…”