In light of the worthy design flexibility and the good signal amplification capacity, the recently developed DNA motor (especially the DNA walker)-based fluorescent biosensors can offer an admirable choice for realizing bioimaging. However, this attractive biosensing strategy not only has the disadvantage of uncontrollable initiation but also usually demands the supplement of exogenous driving forces. To handle the above obstacles, some rewarding solutions are proposed here. First, on the surface of an 808 nm near-infrared light-excited low-heat upconversion nanoparticle, a special ultraviolet upconversion luminescence-initiated threedimensional (3D) walking behavior is performed by embedding a photocleavage linker into the sensing elements, and such lightcontrolled target recognition can perfectly overcome the pre-triggering of the biosensor during the biological delivery to significantly boost the sensing precision. After that, a peculiar self-driven walking pattern is constructed by employing MnO 2 nanosheets as an additional nanovector to physically absorb the sensing frame, for which the reduction of the widespread glutathione in the biological medium can bring about sufficient self-supplied Mn 2+ to guarantee the walking efficiency. By selecting an underlying next-generation broad-spectrum cancer biomarker (survivin messenger RNA) as the model target, we obtain that the newly formed autonomous 3D DNA motor shows a commendable sensitivity (where the limit of detection is down to 0.51 pM) and even an outstanding specificity for distinguishing single-base mismatching. Beyond this sound assay performance, our sensing approach is capable of working as a powerful imaging platform for accurately operating in various living specimens such as cells and bodies, showing a favorable diagnostic ability for cancer care.

Although DNA nanotechnology is a promising option for fluorescent biosensors to perform bioimaging, the uncontrollable target identification during biological delivery and the spatially free molecular collision of nucleic acids may cause unsatisfactory imaging precision and sensitivity, respectively. Aiming at solving these challenges, we herein integrate some productive notions. On the one hand, the target recognition component is inserted with a photocleavage bond and a core–shell structured upconversion nanoparticle with a low thermal effect is further employed to act as the ultraviolet light generation source, under which a precise near-infrared photocontrolled sensing is achieved through a simple external 808 nm light irradiation. On the other hand, the collision of all of the hairpin nucleic acid reactants is confined by a DNA linker to form a six-branched DNA nanowheel, after which their local reaction concentrations are vastly enhanced (∼27.48 times) to induce a special nucleic acid confinement effect to guarantee highly sensitive detection. By selecting a lung cancer-associated short noncoding microRNA sequence (miRNA-155) as a model low-abundance analyte, it is demonstrated that the newly established fluorescent nanosensor not only presents good in vitro assay performance but also exhibits a high-performance bioimaging competence in live biosystems including cells and mouse body, propelling the progress of DNA nanotechnology in the biosensing field.

As a result of inaccurate biosensing and difficult synergetic loading, it is challenging to further impel DNA amplifiers to perform therapeutic application. Herein, we introduce some innovative solutions. First, a smart light-driven biosensing concept based on embedding nucleic acid modules with a simple photocleavagelinker is proposed. In this system, the target identification component is exposed on irradiation with ultraviolet light, thus avoiding an always-on biosensing response during biological delivery. Further, in addition to providing controlled spatiotemporal behavior and precise biosensing information, a metal−organic framework is used for the synergetic loading of doxorubicin in the internal pores, whereafter a rigid DNA tetrahedron-sustained exonuclease III-powered biosensing system is attached to prevent drug leakage and enhance resistance to enzymatic degradation. By selecting a next-generation breast cancer correlative noncoding microRNA biomarker (miRNA-21) as a model low-abundance analyte, a highly sensitive in vitro detection ability even allowing to distinguish single-base mismatching is demonstrated. Moreover, the all-in-one DNA amplifier shows excellent bioimaging competence and good chemotherapy efficacy in live biosystems. These findings will drive research into the use of DNA amplifiers in diagnosis and therapy integrated fields.

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