On-Site Multiply Stimulated Self-Confinement of an Integrated DNA Cascade Circuit for Highly Reliable Intracellular Imaging of miRNA and In Situ Interrogation of the Relevant Regulatory Pathway.

Artificial DNA circuits represent a versatile yet promising toolbox for in situ monitoring and concomitant regulation of diverse biological events within live cells. Nonetheless, their performance is significantly impeded by the diffusion-dominated slow reaction kinetics and the uncontrollable off-target activation. Herein, a self-localized cascade (SLC) circuit is reported for the robust and efficient microRNA (miRNA) analysis in living cells.

Dual-Signal Cascaded Nucleic Acid Amplification Circuit-Loaded Metal-Organic Frameworks for Accurate and Robust Imaging of Intracellular MicroRNA.

Cascaded signal amplification technologies play an important role in the sensitive detection of lowly expressed biomarkers of interests yet are constrained by severe background interference and low cellular accessibility. Herein, we constructed a metal-organic framework-encapsulating dual-signal cascaded nucleic acid sensor for precise intracellular miRNA imaging. ZIF-8 nanoparticles load and deliver FAM-labeled upstream catalytic hairpin assembly (CHA) and Cy5-modified downstream hybridization chain reaction (HCR) hairpin reactants to tumor cells, enabling visualization of the target-initiated signal amplification process for double-insurance detection of analytes.

Chemiluminescence resonance energy transfer-based multistage nucleic acid amplification circuits for MiRNA detection with low background.

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.

An Intelligent Laser-Free Photodynamic Therapy Based on Endogenous miRNA-Amplified CRET Nanoplatform.

Laser-free photodynamic therapy (PDT) is a promising noninvasive therapeutic modality for deep-seated tumor, yet is constrained by low efficiency due to the limited stimulation strategies. Herein, a novel miRNA-responsive laser-free PDT was developed through metal-organic frameworks (MOFs)-mediated chemiluminescence resonance energy transfer (CRET) nanoplatform. The photosensitizer chlorin e6 (Ce6)-loaded MOFs were functionalized with hairpin nucleic acids for sensitive responsiveness of tumor biomarker miRNA through catalytic hairpin assembly (CHA), which enabled the amplified assembly of horseradish peroxidase (HRP)-mimicking hemin/G-quadruplex DNAzyme on MOFs.

Acid-improved DNAzyme-based chemiluminescence miRNA assay coupled with enzyme-free concatenated DNA circuit.

DNAzyme-based chemiluminescence assay exhibits excellent performance in bioanalysis but their operation in acid conditions remains challengeable. Herein, we constructed an acid-improved DNAzyme-based isothermal enzyme-free concatenated DNA circuit with significantly reduced background and simultaneously improved signal-to-noise ratio for miRNA detection. The chemiluminescence miRNA assay is composed of catalyzed hairpin assembly (CHA), hybridization chain reaction (HCR), and hemin/G-quadruplex DNAzyme units.

Intelligent Tumor Microenvironment-Activated Multifunctional Nanoplatform Coupled with Turn-on and Always-on Fluorescence Probes for Imaging-Guided Cancer Treatment.

Intrinsic tumor microenvironment (TME)-related therapeutic resistance and nontumor-specific imaging have limited the application of imaging-guided cancer therapy. Herein, a TME-responsive MnO-based nanoplatform coupled with turn-on and always-on fluorescence probes was designed through a facile biomineralization method for imaging-guided photodynamic/chemodynamic/photothermal therapy (PDT/CDT/PTT). After the tumor-targeting delivery of the AuNCs@MnO-ICG@AS1411 (AMIT) nanoplatform via aptamer AS1411, the TME-responsive dissociation of MnO generated sufficient O and Mn with the consumption of GSH for improving PDT efficacy and Fenton-like reaction-mediated CDT.