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Chemiluminescence resonance energy transfer (CRET)-based assays have shown great potential in biosensing due to their negligible background autofluorescence, yet are still limited by their low sensitivity and short half-life luminescence. Herein, a multistage CRET-based DNA circuit was constructed with amplified luminescence signals for accurate miRNA detection and fixed reactive oxygen species (ROS) signals for cell imaging. The DNA circuit is designed through an ingenious programmable catalytic hairpin assembly (CHA), hybridization chain reaction (HCR), and the use of DNAzyme to realize target-triggered precise regulation of distance between the donor and acceptor for CRET-mediated excitation of photosensitizers. In detail, the analyte catalyzes the hybridization of CHA reactants, which leads to the assembly of multiple HCR-mediated DNAzyme nanowires. Subsequently, DNAzymes catalyze the oxidation of luminol by H2O2, and the adjacent photosensitizer chlorin e6 (Ce6) anchored on the DNA nanostructure is stimulated by the CRET process, resulting in the amplified long-wavelength luminescence and the generation of single oxygen signals through further energy transfer to oxygen. The biomarker miRNA can be detected with great sensitivity by integrating the recognition module into a universal platform. Furthermore, the DNA circuit enables CRET-mediated intracellular miRNA imaging, by detecting singlet oxygen signals through a ROS probe. The significant amplification effect is attributed to the robust multiple recognition of the target and the guaranteed transduction of the CRET signal through programmable engineering of DNA nanostructures. The CRET-based DNA circuit achieves amplified long-wavelength luminescence for accurate miRNA detection with low background and ROS-mediated signal fixation for cell imaging, making it a promising candidate for early diagnosis and theranostics. [ABSTRACT FROM AUTHOR]

Herein, we developed a reliable and portable biosensor (TDR-PGM nanomachine) for the sensitive detection of microRNA by integrating an efficient toehold-mediated strand displacement reaction module (TDR) and a personal glucose meter (PGM). The system provides a versatile methodology for microRNA detection in real samples and holds broad prospects in point-of-care diagnosis. [ABSTRACT FROM AUTHOR]

A versatile approach for the fine control of DNA-based hierarchical assembly via dual stimuli and two assembly strategies is developed. Moreover, with a reasonable design of functional thrombin aptamer structures on the formed DNA nanoassembly, it can achieve precise regulation of thrombin activity. [ABSTRACT FROM AUTHOR]

The autocatalytic HCR-DNAzyme platform was constructed as a versatile amplification platform for intracellular microRNA imaging by integrating hybridization chain reaction (HCR) circuit with DNAzyme biocatalysis. The HCR-assembled multifunctional DNAzyme nanowires produce new HCR triggers and numerous transducer DNAzyme amplifier, and thus shows great promise in earlier cancer diagnosis. [ABSTRACT FROM AUTHOR]

Benefiting from the simple DNAzyme and a duplex-specific nuclease, a series of microRNA-stimulated DNAzyme logic gates were rationally assembled for the highly accurate detection of multiple low-abundant microRNA biomarkers that correspond to the specific aberrant microRNA expression patterns of cancer tissues, thus showing a great potential in early diagnosis. [ABSTRACT FROM AUTHOR]

A facile cross-catalytic circuit is engineered for intracellular microRNA (miRNA) imaging by facilely integrating a catalytic hairpin assembly (CHA) amplifier and DNAzyme biocatalyst through an ingenious feedback loop. These two indispensable catalytic reactions play vital roles in executing high-performance signal amplification, as demonstrated experimentally and theoretically. [ABSTRACT FROM AUTHOR]

Construction of stimuli-responsive multifunctional nanoparticles is critical for nanotherapeutic delivery. Though metal–organic frameworks (MOFs) have been emerged as promising delivery vehicles, the therapeutic efficacy of MOFs in cancer treatment is limited by the lack of a general approach for the preparation of stimuli-responsive multifunctional MOFs. We show that the combination of a versatile coating material polydopamine with MOFs enables facile integration of different functional therapeutics, obtaining stimuli-responsive multifunctional MOFs with extensive photothermal efficiency and outstanding capability to abrogate tumors by chemo-photothermal therapy. Exemplary MOFs including ZIF-8, UiO-66, and MIL-101 were utilized to prepare stimuli-responsive multifunctional MOFs to illustrate the generality of the strategy. This approach enables targeted drug delivery and stimuli-responsive release of multi-therapeutics and allows combination therapy with excellent in vitro and in vivo antitumor activity. Taking into account the diversity of MOFs and different functional molecules, this work provides flexible access to programmable MOF nanoparticles for specific biological applications. [ABSTRACT FROM AUTHOR]

An autonomous nonenzymatic DNA machine has been successfully engineered based on a two-layered cascaded hybridization chain reaction (C-HCR) circuit, in which the tandem outputs of the upstream HCR-1 unit activate the downstream HCR-2 unit to induce successive repeated hybridizations, generating branched DNA structures and enabling sensitive and selective detection of uracil-DNA glycosylase and its inhibitors. [ABSTRACT FROM AUTHOR]

The photonic- and redox-triggered cyclic uptake and release of organic substrates in functionalized mesoporous SiO2 nanoparticles (NPs) is demonstrated. The mesoporous SiO2 NPs are functionalized with nitrospiropyran photoisomerizable units. Rhodamine B is encapsulated in the channels of the SiO2 NPs and trapped by the hydrophobic nitrospiropyran capping units. Photoisomerization of the capping units to the protonated nitromerocyanine groups opens the channels and releases the encapsulated dye. Similarly, modification of the SiO2 channels by chloronaphthoquinone units traps eosin Y in the channels, by means of donor–acceptor interactions. The reduction of the quinone units to the chloronaphth hydroquinone donor groups opens the channels and releases the encapsulated substrate. The novelty of the study rests on the demonstration of the reversible and cyclic photostimulated or redox-activated uptake and release of substrates from the mesoporous SiO2 NPs. [ABSTRACT FROM AUTHOR]

Glucose assay is highly important in clinical diagnostics of diabetes. Herein, we engineered the surface of carbon dots by complexation with functional ligand and constructed fluorescent biosensors for the detection of hydrogen peroxide and glucose. In this study, benzenediboronic acid is conjugated to the surface of citric acid-derived carbon dots through formation of boronate complexes with the nanoparticles. The oxidation of benzenediboronic acid with hydrogen peroxide effectively quenches fluorescence of carbon dots through electron transfer process. The sensing performance of the system according to different engineered surfaces of carbon dots was studied by using carbon dots derived from various precursors and different benzenediboronic acid analogues. As a simple mix-and-detect strategy, this system is facilely applied for glucose sensing as hydrogen peroxide is the product catalyzed by glucose oxidase. The benzenediboronic acid-conjugated carbon dots derived from citric acid act as excellent optical probes for sensitive analysis of glucose with detection limit of 0.4 μM. This sensing system shows great selectivity toward interferent species such as analogues of glucose, and can be used to determine glucose in human serum. Engineering the surface of carbon dots by complexation with ligand of interest provides a feasible way to facilitate the development of biological applications., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Biomolecular self-assembly has spurred substantial research efforts for the development of low-cost point-of-care diagnostics. Herein, we introduce an isothermal enzyme-free concatenated hybridization chain reaction (C-HCR), in which the output of the upstream hybridization chain reaction (HCR-1) layer acts as an intermediate input to activate the downstream hybridization chain reaction (HCR-2) layer. The initiator motivates HCR-1 through the autonomous cross-opening of two functional DNA hairpins, yielding polymeric dsDNA nanowires composed of numerous tandem triggers T as output of the primary sensing event. The reconstituted amplicon T then initiates HCR-2 and transduces the analyte recognition into an amplified readout, originating from the synergistic effect between HCR-1 and HCR-2 layers. Native gel electrophoresis, atom force microscopy (AFM) and fluorescence spectra revealed that C-HCR mediated the formation of frond-like branched dsDNA nanowires and the generation of an amplified FRET signal. As a versatile and robust amplification strategy, the unpreceded C-HCR can discriminate DNA analyte from its mutants with high accuracy and specificity. By incorporating an auxiliary sensing module, the integrated C-HCR amplifier was further adapted for highly sensitive and selective detection of microRNA (miRNA), as a result of the hierarchical and sequential hybridization chain reactions, in human serum and even living cells through an easy-to-integrate "plug-and-play" procedure. In addition, the C-HCR amplifier was successfully implemented for intracellular miRNA imaging by acquiring an accurate and precise signal localization inside living cells, which was especially suitable for the ex situ and in situ amplified detection of trace amounts of analyte. The C-HCR amplification provides a comprehensive and smart toolbox for highly sensitive detection of various biomarkers and thus should hold great promise in clinical diagnosis and assessment. The infinite layer of multilayered C-HCR is anticipated to further strengthen the amplification capacity and reliability (anti-invasion performance) of intracellular imaging approach, which is of great significance for its bioanalytical applications.

The pH-controlled release of substrates from mesoporous SiO 2 nanoparticles, MP-SiO 2 NPs, is demonstrated by capping the pores with the Mg 2+ - or UO 2 2+ -dependent DNAzyme sequences and unlocking of the pores with Mg 2+ ions or UO 2 2+ ions at appropriate pH values. While the Mg 2+ -dependent DNAzyme reveals high activity at pH = 7.2, moderate activity at pH = 6.0, and it lacks activity at pH = 5.2, the UO 2 2+ -dependent DNAzyme reveals high activity at pH = 5.2, moderate activity at pH = 6.0, and it is catalytically inactive at pH = 7.2. Accordingly, the MP-SiO 2 NPs were loaded with methylene blue, MB + , or thionine, Th + , and locked in the pores by the Mg 2+ - and UO 2 2+ -dependent DNAzyme sequences, respectively. The pH-programmed release of MB + or Th + from the loaded NPs proceeds, in the presence of Mg 2+ ions or UO 2 2+ ions, at pH = 7.2 and pH = 5.2, using the Mg 2+ - and UO 2 2+ -dependent DNAzyme as catalysts that cleave the protecting caps and unlock the pores, respectively. At pH = 6.0 the MB + - and Th + -loaded NPs are concomitantly unlocked by the two DNAzymes. The unlocking processes are selective and other metal ions do not stimulate the release processes.

The photonic- and redox-triggered cyclic uptake and release of organic substrates in functionalized mesoporous SiO 2 nanoparticles (NPs) is demonstrated. The mesoporous SiO 2 NPs are functionalized with nitrospiropyran photoisomerizable units. Rhodamine B is encapsulated in the channels of the SiO 2 NPs and trapped by the hydrophobic nitrospiropyran capping units. Photoisomerization of the capping units to the protonated nitromerocyanine groups opens the channels and releases the encapsulated dye. Similarly, modification of the SiO 2 channels by chloronaphthoquinone units traps eosin Y in the channels, by means of donor-acceptor interactions. The reduction of the quinone units to the chloronaphth hydroquinone donor groups opens the channels and releases the encapsulated substrate. The novelty of the study rests on the demonstration of the reversible and cyclic photostimulated or redox-activated uptake and release of substrates from the mesoporous SiO 2 NPs.