A nanoflare, a conjugate of Au nanoparticles (NPs) and fluorescent nucleic acids, is believed to be a powerful nanoplatform for diagnosis and therapy. However, it highly suffers from the nonspecific detachment of nucleic acids from the AuNP surface because of the poor stability of Au−S linkages, thereby leading to the false-positive signal and serious side effects. To address these challenges, we report the use of covalent amide linkage and functional Au@graphene (AuG) NP to fabricate a covalent conjugate system of DNA and AuG NP, label-rcDNA-AuG. Covalent coating of abundant amino groups (−NH 2 ) onto the graphitic shell of AuG NP efficiently facilitates the coupling with carboxyl-labeled capture DNA sequences through simple, but strong, amide bonds. Importantly, such an amidebonded nanoflare possesses excellent stability and anti-interference capability against the biological agents (nuclease, DNA, glutathione (GSH), etc.). By accurately monitoring the intracellular miR-21 levels, this covalent nanoflare is able to identify the positive cancer cells even in a mix of cancer and normal cells. Moreover, it allows for efficient photodynamic therapy of the targeted cancer cells with minimized side effects on normal cells. This work provides a facile approach to develop a superstable nanosystem showing promising potential in clinical diagnostics and therapy.

Accurate identification of cancer cells is an essential prerequisite for cancer diagnosis and subsequent effective curative interventions. The logic-gate-assisted cancer imaging system that allows a comparison of expression levels between biomarkers, rather than just reading biomarkers as inputs, returns a more comprehensive logical output, improving its accuracy for cell identification. To fulfill this key criterion, we develop a compute-and-release logic-gated double-amplified DNA cascade circuit. This novel system, CAR-CHA-HCR, consists of a compute-and-release (CAR) logic gate, a double-amplified DNA cascade circuit (termed CHA-HCR), and a MnO 2 nanocarrier. CAR-CHA-HCR, a novel adaptive logic system, is designed to logically output the fluorescence signals after computing the expression levels of intracellular miR-21 and miR-892b. Only when miR-21 is present and its expression level is above the threshold C miR-21 > C miR-892b , the CAR-CHA-HCR circuit performs a compute-andrelease operation on free miR-21, thereby outputting enhanced fluorescence signals to accurately image positive cells. It is capable of comparing the relative concentrations of two biomarkers while sensing them, thus allowing accurate identification of positive cancer cells, even in mixed cell populations. Such an intelligent system provides an avenue for highly accurate cancer imaging and is potentially envisioned to perform more complex tasks in biomedical studies.

Quantifying the miRNAs levels in living cells, while essential for the study of fundamental biology and medical diagnostics, has barely been achieved due to insufficient probe delivery and unquantifiable signals. We report a cell-anchored and self-calibrated DNA nanoplatform, a cholesterol-headed DNA nanowire, that is capable of efficiently delivering into various cells and simultaneously detecting two target miRNAs. One miRNA target can be utilized as an endogenous control against cell-to-cell variations. Moreover, the PC-linkers inserted in the nanostructures allow us to precisely regulate the probe structure and fluorescence signaling at the desired time and location in vivo. As a second control, the maximum fluorescence can be elicited by UV light, which further facilitates the normalization of the absolute fluorescence signal. With two introduced internal controls, the maximum fluorescence and endogenous control gene, this approach displays excellent stability and selfcalibration performance, effectively shielding the influences of operating conditions and cell-to-cell variations,

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