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Dual-mode signal output platforms have demonstrated considerable promise due to their improved anti-interference capability and inherent signal self-correction. Nevertheless, traditional discrete-distributed signal probes often encounter significant drawbacks, including limited mass transfer efficiency, diminished signal strength, and instability in intricate biochemical environments. In response to these challenges, a scalable and hyper-compacted 3D DNA nanoplatform resembling "periodic focusing heliostat" has been developed for synergistically enhanced fluorescence (FL) and surface-enhanced Raman spectroscopy (SERS) biosensing of miRNA in cancer cells. Our approach utilized a distinctive assembly strategy integrating gold nanostars (GNS) as fundamental "heliostat units" linked by palindromic DNA sequences to facilitate each other hand-in-hand cascade alignment and condensed into large scale nanostructures. This configuration was further augmented by the incorporation of gold nanoparticles (GNP) via strong Au-S bonds, resulting in a sturdy framework for improved signal transduction. The initiation of this assembly process was mediated by the hybridization of dsDNA to miRNA-21, which served as a primer for polymerization and nicking reactions, thus generating a multifunctional T2 probe. This probe is intricately designed with three distinct parts: a 3'-palindromic end for structural integrity, a central region for capturing SERS-active probes (Cy3-P2), and a 5'-segment for attaching fluorescence reporters. Upon integration T2 into the GNS-based heliostat unit, it promotes palindromic arm-induced aggregation and plasma exciton coupling between plasma nanoparticles and signal transduction tags. This clustered arrangement creates a high-density "hot spot" array that maximizes the local electromagnetic fields necessary for enhanced SERS and FL response. This superstructure supports enhanced aggregation-induced signal amplification for both SERS and FL, offering exceptional sensitivity with LOD as low as 0.0306 pM and 0.409 pM. The efficacy of this method was demonstrated in the evaluation of miRNA-21 in various cancer cell lines., Competing Interests: Declaration of competing interest The authors declared that they have no conflicts of interest to this work., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Poly(ADP-ribose) polymerase-1 (PARP-1), as an original tumor marker, has aroused wide attention in recent years. However, only a few researches have been done for PARP-1 activity detection because PARP-1 is lack of optical or electrochemical property. In this work, a label-free and high-sensitive photoelectrochemical (PEC) biosensor for PARP-1 activity detection based on poly[9,9-bis(6'-N,N,N-trimethylammonium)hexyl]fluorenylene phenylene (PFP) has been designed. To the best of our knowledge, it is the first time that PEC has been used to monitor PARP-1 activity. PARP-1 were activated under the function of activated dsDNA, as a result, branched polymers of ADP-ribose (PAR) with plentiful negative charge were formed in the presence of nicotinamide adenine dinucleotide (NAD + ). Subsequently, positively charged PFP with good photoelectrochemical properties, were absorbed on PAR via electrostatic interaction. High photocurrent was produced under light induction, which was depended on the PARP-1 activity. The biosensor has a wide linear range from 0.01 to 2 U with a detection limit of 0.007 U. The strategy has been applied in breast and ovarian cancer cells to detection PARP-1 activity with approving results, which signifies that it is a promising tool for clinical diagnosis., (Copyright © 2019. Published by Elsevier B.V.)

The cellular enzyme poly ADP (ADP: adenosine diphosphate)-ribose polymerase-1 (PARP-1) plays key roles in DNA repair. Its activity is closely related to various cancer developments. Detection of PARP-1 activity is significant, however, it is relatively difficult since it lacks superiority property that can be used to detect conveniently. PARP-1 lead to the synthesis of hyperbranched poly (ADP-ribose) polymers (PAR) using nicotinamide adenine dinucleotide (NAD + ) as substrate during DNA damage repairing. In this paper, we found that hyper-branched PAR increased the steric hindrance and reduced the flux of probe ions effectively in anodic aluminum oxide (AAO) nanochannels. To the best of our knowledge, few papers have been reported that hyper-branched polymer has the similar effects in nanochannels as G-quadruplex DNA. Thus, a novel and simple strategy for PARP-1 detection has been proposed due to its great impacts on the diffusion flux of ferricyanide in AAO. It is also proved that electrostatic repulsion is another important factor to influence the current. The method is label-free, simple and sensitive. Quantitative detection of PARP-1 activity was achieved with the detection limit of 0.006 U, which is lower or comparable to the most reported methods. The method has good accuracy and reproducibility. The strategy has been used to detect PARP-1 activity in real breast cancer cells and to evaluate PARP-1 inhibitors with satisfactory results, indicating that it is a potential powerful tool for clinical diagnosis and drug development in the future., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Telomerase has become one of the most typical tumor marker because it is closely related to cancers. In this paper, a simple label-free electrochemical detection of telomerase activity by using methylene blue (MB) as a G-quadruplex binding probe was proposed, avoiding commonly used complex label procedures, nano-probe synthesis, complicated electrode modification, probe immobilization or signal amplification. In the presence of telomerase substrate (TS) primer, the binding of MB on primer was weak. When repeats of (TTAGGG) were extended on the TS primer under the action of telomerase, they formed multiple G-quadruplexes with the help of K + . As a result, a large amount of MB bounded to multiple G-quadruplexes because they have more strong interaction with G-quadruplexes than TS primer. As a result, the diffusion current of MB decreased sharply, which was strongly dependent on the telomerase activity. The DPV current change has a linear correlation with the logarithm of HeLa cell number in the range of 10-10,000 cells, with the detection limit of 3 cells. The high sensitivity was due to the formed multiple G-quadruplexes. Using indium tin oxide (ITO) as working electrode without modification ensured the good reproducibility of the method. The method was also simple, rapid, and has been successfully applied in the telomerase activity detection in urine with good selectivity and reproducibility, which is significant for cancer diagnosis, anticancer drugs screening, and cancer therapy evaluation., (Copyright © 2016 Elsevier B.V. All rights reserved.)