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Synthetic biochemical circuits (e.g., DNA circuits) remain at the forefront of intracellular biosensing tasks yet are hindered by the undesired off‐site activation and the accompanying signal leakage. Herein, the study attempts to overcome this limitation by developing a simple‐yet‐powerful endogenous glutathione (GSH)‐regulating tactic that permits robust and distinguishable on‐site microRNA (miRNA) imaging under disturbed redox homeostasis. Specifically, a hierarchically activated catalytic DNA (HAD) circuit is fabricated by grafting the disulfide linkage within entropy‐driven DNA circuitry (EDC) reactants. It is exemplified that this HAD system promises the spatiotemporally selective microRNA‐21 (miR‐21) imaging in living cells and the robust differentiation of tumor cells from normal cells. The correlationship between GSH and miRNA is extensively explored in live cells, and can substantially expand the toolbox of DNA circuits for profiling intracellular biochemical processes. [ABSTRACT FROM AUTHOR]

Non‐invasive cell regulation represents a promising approach for on‐site cell modulation, but is confronted with inaccuracy or poor cell selectivity. Herein, by virtue of the interfacial‐activated concatenate DNA circuit, an activated recombination‐to‐modulation (ARM) machinery is developed to achieve accurate membrane imaging and effective cell modulation. Bioorthogonal signal transduction through the catalytic hairpin assembly circuit can continuously regenerate triggers for activating the subsequent circuit, with no activator consumption and occupation. The ARM strategy utilizes the amplified hybridization chain reaction to sensitively rearrange membrane receptors for blocking the related signaling pathways and indirectly modulating cell behaviors. Based on these two membrane receptor inputs, the controllably‐activated ARM strategy enables the identification of target cells among similar interfering cells with high accuracy and sensitivity. This machinery has demonstrated good performance in the efficient inhibition of tumor metastasis via the disruption of HGF/c‐Met‐signaling pathway. The modular‐designed ARM machinery provides a general platform for non‐invasive and specific cell modulation, suggesting a broad opportunity for advanced exploration of cellular metabolism behaviors. [ABSTRACT FROM AUTHOR]

The K+-induced formation of G-quadruplexes provides a versatile motif to lock or unlock substrates trapped in the pores of mesoporous SiO2 nanoparticles, MP-SiO2 NPs. In one system, the substrate is locked in the MP-SiO2 NPs by K+-ion-stabilized G-quadruplex units, and the pores are unlocked by the elimination of K+ ions using Kryptofix [2.2.2] (KP) or 18-crown-6-ether (CE) from the G-quadruplexes. In the second system, the substrate is locked in the pores by means of K+-stabilized aptameric G-quadruplex/thrombin units. Unlocking of the pores is triggered by the dissociation of the aptamer/thrombin complexes through the KP- or CE-mediated elimination of the stabilizing K+ ions. In the third system, duplex DNA units lock the pores of MP-SiO2 NPs, and the release of the entrapped substrate is stimulated by the K+-ion-induced dissociation of the duplex caps through the formation of the K+-stabilized G-quadruplexes. The latter system is further implemented to release the anti-cancer drug, doxorubicin, in the presence of K+ ions, from the MP-SiO2 NPs. Preliminary intracellular experiments reveal that doxorubicin-loaded MP-SiO2 NPs lead to effective death of breast cancer cells. [ABSTRACT FROM AUTHOR]

On page 5662, I. Willner and team show how K+‐ion‐stabilized G‐quadruplexes act as locks for the entrapment of substrates in mesoporous silica nanoparticles. The pores are unlocked by the Kryptofi × [2.2.2] (KP) through the removal of the K+ ions. Also, programmed duplex structures lock the anticancer drug doxorubicin in mesoporous silica nanoparticles. The pores are unlocked by the separation of the duplex through the formation of a G‐quadruplex. [ABSTRACT FROM AUTHOR]