Self-Powered Engineering of Cell Membrane Receptors to On-Demand Regulate Cellular Behaviors.

On-demand engineering of cell membrane receptors to nongenetically intervene in cellular behaviors is still a challenge. Herein, a membraneless enzyme biofuel cell-based self-powered biosensor (EBFC-SPB) was developed for autonomously and precisely releasing Zn2+ to initiate DNAzyme-based reprogramming of cell membrane receptors, which further mediates signal transduction to regulate cellular behaviors. The critical component of EBFC-SPB is a hydrogel film on a biocathode which is prepared using a Fe3+-cross-linked alginate hydrogel film loaded with Zn2+ ions. In the working mode in the presence of glucose/O2, the hydrogel is decomposed due to the reduction of Fe3+ to Fe2+, accompanied by rapid release of Zn2+ to specifically activate a Zn2+-responsive DNAzyme nanodevice on the cell surface, leading to the dimerization of homologous or nonhomologous receptors to promote or inhibit cell proliferation and migration. This EBFC-SPB platform provides a powerful "sensing-actuating-treating" tool for chemically regulating cellular behaviors, which holds great promise in precision biomedicine.

Pyroelectric-Effect-Assisted Near-Infrared-Driven Photoelectrochemical Biosensor Based on Exponential DNA Amplifier for MicroRNA Detection.

Although near-infrared responsive photoelectrochemical (PEC) biosensors have less damage to biological components compared to UV-visible light, they still reveal an inferior response due to the rapid recombination of photogenerated electron-hole. In this study, a near-infrared-driven PEC biosensor is fabricated for microRNA (miRNA) detection via integrating photoelectricity and pyroelectricity. Upon the introduction of target miRNA-21, the exponential DNA amplifier is triggered based on enzyme-assisted strand displacement amplification (SDA), releasing multiple Ag2S reporter probes to hybridize with capture probes immobilized on a CdS-2-mercaptobenzimidazole (2MBI)-modified photoelectrode. As a result, under the stimulation of NIR, the photoelectric conversion of Ag2S NPs generates the photocurrents. In addition, due to the strong hole acceptor ability of MBI, the pyroelectric effect of CdS-2MBI nanocomposites is enhanced, which generates highly pyroelectro-induced charge separation efficiency and induces the pyroelectric current benefited from the spontaneous polarization of CdS-2MBI caused by the temperature variation under the function of Ag2S nanoheaters. Impressively, this PEC biosensor has achieved the sensitive and selective determination of miRNA-21 with a detection limit as low as 54 fM. Overall, this NIR-driven PEC biosensor based on pyroelectric and photoelectric effects opens up a new horizon for bioanalysis and early disease diagnosis.

Hierarchical Porous Metal-Organic Framework as Biocatalytic Microreactor for Enzymatic Biofuel Cell-Based Self-Powered Biosensing of MicroRNA Integrated with Cascade Signal Amplification.

Enzymatic biofuel cells have become powerful tools in biosensing, which however generally suffer from the limited loading efficiency as well as low catalytic activity and poor stability of bioenzymes. Herein, the hierarchical porous metal-organic frameworks (MOFs) are synthesized using tannic acid (TA) for structural etching, which realizes co-encapsulation of glucose dehydrogenase (GDH) and nicotinamide adenine dinucleotide (NAD+ ) cofactor in zeolitic imidazolate framework (ZIF-L) and are further used as the biocatalytic microreactors to modify bioanode. In this work, the TA-controlled etching can not only expand the pore size of microreactors, but also achieve the reorientation of enzymes in their lower surface energy form, therefore enhancing the biocatalysis of cofactor-dependent enzyme. Meanwhile, the topological DNA tetrahedron is assembled on the microreactors, which acts as the microRNA-responsive "lock" to perform the cascade signal amplification of exonuclease III-assisted target recycling on bioanode and hybridization chain reaction (HCR) on biocathode. The proposed self-powered biosensor has achieved a detection limit as low as 2 aM (6 copies miRNA-21 in a 5 µL of sample), which is further successfully applied to identify cancer cells and clinical serums of breast cancer patients based on the different levels of miRNA-21, holding great potential in accurate disease identification and clinical diagnosis.

Upconversion Nanoparticle@Au Core-Satellite Assemblies for In Situ Amplified Imaging of MicroRNA in Living Cells and Combined Cancer Phototherapy.

Stimuli-responsive therapy of cancer with spatial and temporal control is crucial in improving the treatment efficacy and minimizing the side effects. MicroRNA (miRNA) as an important biomarker has become one of the most promising endogenous stimuli for cancer therapy. However, the therapy efficacy is often impeded by the low expression amount of miRNA. Herein, the upconversion nanoparticle@Au (UCNP@Au) core-satellite nanostructures are rationally fabricated for isothermal amplification detection and in situ imaging of microRNA-21 (miR-21) in living cells based on the toehold-mediated strand displacement (TMSD) reaction, which is further applied to miRNA-responsive combined photothermal and photodynamic therapy of breast cancer. The UCNP@Au are constructed by linking AuNPs to photosensitizers Rose Bengal (RB)-loaded UCNPs through DNA hybridization. The upconversion luminescence (UCL) is quenched by AuNPs, resulting in the attenuation of singlet oxygen generation of RB. Once UCNP@Au are internalized into MCF-7 cells, the overexpressed intracellular miR-21 trigger the cyclic disassembly of UCNP@Au through cascade TMSD reactions, which facilitate the restoration of UCL for in situ imaging of miR-21 with signal amplification. Moreover, the released AuNPs are aggregated for photothermal therapy (PTT), while the singlet oxygen generated by RB is enhanced for photodynamic therapy (PDT). Compared with single-mode therapy, the miRNA-activated combinational phototherapy has demonstrated a greatly improved therapeutic efficacy for breast cancer. Therefore, our proposed core-satellite nanostructures cannot only achieve in situ amplified imaging of endogenous miRNA but also provide an effective nanoplatform for stimuli-responsive combinational phototherapy, which hold great prospects in early diagnosis and treatment of cancers.

Biometric Photoelectrochemical-Visual Multimodal Biosensor Based on 3D Hollow HCdS@Au Nanospheres Coupled with Target-Induced Ion Exchange Reaction for Antigen Detection.

Three-dimensional (3D) hollow photoactive nanomaterials can enhance light capture due to the light scattering benefiting from the unique hollow nanostructures, which contributes to the decrease in energy loss and the electron-hole recombination during the process of photoelectric conversion. Herein, a 3D hollow HCdS@Au nanosphere synthesized by the templated-assisted method and photodeposition is employed to construct a multimodal sensing platform by combining the photoelectrochemical (PEC) biosensor with colorimetric analysis and photothermal imaging. In the presence of target carcinoembryonic antigen (CEA), a sandwich structure is formed on magnetic beads based on the dual-aptamer recognition, followed by the initiation of rolling circle amplification (RCA) to bind numerous CuO-DNA probes. Upon stimulation by chlorhydric acidic, a large number of Cu2+ is released from CuO, which could interact with yellow HCdS@Au on electrode to produce dark CuS by ion exchange. As a result, with increased CEA level, the photocurrent is weakened and the color of electrode interface is changed from yellow to dark, which thus facilitates the PEC and colorimetric detection of CEA. Simultaneously, the formed CuS with highly photothermal effect can achieve qualitative visual analysis of CEA using a portable infrared thermal imager. This work exhibits an excellent performance for sensitive and selective detection of CEA in the dynamic working range from 0.015 to 2.4 ng/mL with a detection limit as low as 3.5 pg/mL. Moreover, the proposed PEC biosensor is successfully applied to CEA determination in human serum, which holds great promise in accurate analysis of biomarkers and early diagnosis of diseases in the clinic.

Trimetallic AuPtCo Nanopolyhedrons with Peroxidase- and Catalase-Like Catalytic Activity for Glow-Type Chemiluminescence Bioanalysis.

Chemiluminescence (CL) with stable and glowing light emission is vital for the accurate detection of biomarkers. Moreover, the catalyst plays an important role in CL systems. Herein, the trimetallic AuPtCo nanopolyhedrons with peroxidase- and catalase-like catalytic activities are readily synthesized via a one-step reduction method. After reaction with the substrate ABEI and oxidant H2O2, the AuPtCo nanozyme can catalyze the CL emission in a flash type. Interestingly, it has been found that the biofunctionalization of the AuPtCo surface can endow the catalytic interface with a slow-diffusion effect, thereby prolonging the emission of glow-type CL. On this basis, two biofunctionalized AuPtCo nanocomposites, named as AuPtCo@Cys and AuPtCo@Ab, are prepared, achieving sensitive and selective detection of H2O2 and lipoprotein-associated phospholipase A2 (Lp-PLA2), respectively. Further, the proposed glow-type CL assays are successfully applied for the determination of H2O2 and Lp-PLA2 in female vaginal discharge and human serum samples, respectively, which exhibit good correlation with the clinical results. Overall, the trimetallic AuPtCo nanozyme-based glow-type CL analysis has demonstrated as a powerful and robust tool for biomarker analysis, which holds great promise in clinical applications.

Endogenous microRNA triggered enzyme-free DNA logic self-assembly for amplified bioimaging and enhanced gene therapy via in situ generation of siRNAs.

BACKGROUND: Small interfering RNA (siRNA) has emerged as a kind of promising therapeutic agents for cancer therapy. However, the off-target effect and degradation are the main challenges for siRNAs delivery. Herein, an enzyme-free DNA amplification strategy initiated by a specific endogenous microRNA has been developed for in situ generation of siRNAs with enhanced gene therapy effect on cervical carcinoma. METHODS: This strategy contains three DNA hairpins (H1, H2/PS and H3) which can be triggered by microRNA-21 (miR-21) for self-assembly of DNA nanowheels (DNWs). Notably, this system is consistent with the operation of a DNA logic circuitry containing cascaded "AND" gates with feedback mechanism. Accordingly, a versatile biosensing and bioimaging platform is fabricated for sensitive and specific analysis of miR-21 in HeLa cells via fluorescence resonance energy transfer (FRET). Meanwhile, since the vascular endothelial growth factor (VEGF) antisense and sense sequences are encoded in hairpin reactants, the performance of this DNA circuit leads to in situ assembly of VEGF siRNAs in DNWs, which can be specifically recognized and cleaved by Dicer for gene therapy of cervical carcinoma. RESULTS: The proposed isothermal amplification approach exhibits high sensitivity for miR-21 with a detection limit of 0.25 pM and indicates excellent specificity to discriminate target miR-21 from the single-base mismatched sequence. Furthermore, this strategy achieves accurate and sensitive imaging analysis of the expression and distribution of miR-21 in different living cells. To note, compared to naked siRNAs alone, in situ siRNA generation shows a significantly enhanced gene silencing and anti-tumor effect due to the high reaction efficiency of DNA circuit and improved delivery stability of siRNAs. CONCLUSIONS: The endogenous miRNA-activated DNA circuit provides an exciting opportunity to construct a general nanoplatform for precise cancer diagnosis and efficient gene therapy, which has an important significance in clinical translation.

Endogenous mRNA Triggered DNA-Au Nanomachine for In Situ Imaging and Targeted Multimodal Synergistic Cancer Therapy.

The development of versatile nanotheranostic platforms that integrate both diagnostic and therapeutic functions have always been an intractable challenge in precise cancer treatment. Herein, an aptamer-tethered deoxyribonucleic acids-gold particle (Apt-DNA-Au) nanomachine has been developed for in situ imaging and targeted multimodal synergistic therapy of mammary carcinoma. Upon specifically internalized into MCF-7 cells, the tumor-related TK1 mRNA activates the Apt-DNA-Au nanomachine by DNA strand displacement cascades, resulting in the release of the fluorophore and antisense DNA as well as the aggregation of AuNPs for in situ imaging, suppression of survivin expression and photothermal therapy, respectively. Meanwhile, the controlled released drugs are used for chemotherapy, while under the laser irradiation the loaded photosensitizer produces reactive oxygen species (ROS) for photodynamic therapy. The results confirm that the proposed Apt-DNA-Au nanomachine provides a powerful nanotheranostic platform for in situ imaging-guided combinatorial anticancer therapy.

Bioapplications of DNA nanotechnology at the solid-liquid interface.

DNA nanotechnology engineered at the solid-liquid interface has advanced our fundamental understanding of DNA hybridization kinetics and facilitated the design of improved biosensing, bioimaging and therapeutic platforms. Three research branches of DNA nanotechnology exist: (i) structural DNA nanotechnology for the construction of various nanoscale patterns; (ii) dynamic DNA nanotechnology for the operation of nanodevices; and (iii) functional DNA nanotechnology for the exploration of new DNA functions. Although the initial stages of DNA nanotechnology research began in aqueous solution, current research efforts have shifted to solid-liquid interfaces. Based on shape and component features, these interfaces can be classified as flat interfaces, nanoparticle interfaces, and soft interfaces of DNA origami and cell membranes. This review briefly discusses the development of DNA nanotechnology. We then highlight the important roles of structural DNA nanotechnology in tailoring the properties of flat interfaces and modifications of nanoparticle interfaces, and extensively review their successful bioapplications. In addition, engineering advances in DNA nanodevices at interfaces for improved biosensing both in vitro and in vivo are presented. The use of DNA nanotechnology as a tool to engineer cell membranes to reveal protein levels and cell behavior is also discussed. Finally, we present challenges and an outlook for this emerging field.

Cascade Amplification-Mediated In Situ Hot-Spot Assembly for MicroRNA Detection and Molecular Logic Gate Operations.

MicroRNAs (miRNAs) play important roles in many biological processes and are associated with various diseases, especially cancers. Combination of technological developments such as nanomaterials, functional enzyme-mediated reactions, and DNA nanotechnology holds great potential for high-performance detection of miRNAs in molecular diagnostic systems. In this work, we have fabricated a cascade signal amplification platform through integrating duplex-specific nuclease (DSN)-assisted target recycling with catalytic hairpin assembly (CHA) reaction for the detection of microRNA-141 (miR-141). The target recycling process driven by DSN results in highly amplified translation of target miRNA to single-stranded connector DNA fragments. The CHA reaction is further initiated by connector DNAs using hairpin-modified gold nanoparticles (HP-AuNPs) as the sensing unit, leading to the formation of AuNP network architecture on the electrode for electrochemical and photoelectrochemical detection of miR-141 in signal-on and signal-off modes, respectively. The developed electrochemical biosensor exhibits a detection limit down to 25.1 aM miR-141 (60 copies in 4 µL sample) and excellent selectivity to discriminate a single base-mismatched sequence and other miRNAs. This assay is also applied to the determination of miR-141 in total RNAs extracted from human breast cancer cells (MDA-MB-231), confirming the applicability of this method for absolute quantification of specific miRNAs in real-world samples. Furthermore, two-input AND and INHIBIT (INH) logic gates are constructed to detect miRNAs. In particular, the AND gate achieves cell-specific gate activation based on expression profiles of miR-141 and microRNA-21 (miR-21). Therefore, our proposed cascade amplification platform has great potential applications in miRNA-related clinical diagnostics and biochemical research.

Hybridization chain reaction: a versatile molecular tool for biosensing, bioimaging, and biomedicine.

Developing powerful, simple and low-cost DNA amplification techniques is of great significance to bioanalysis and biomedical research. Thus far, many signal amplification strategies have been developed, such as polymerase chain reaction (PCR), rolling circle amplification (RCA), and DNA strand displacement amplification (SDA). In particular, hybridization chain reaction (HCR), a type of toehold-mediated strand displacement (TMSD) reaction, has attracted great interest because of its enzyme-free nature, isothermal conditions, simple protocols, and excellent amplification efficiency. In a typical HCR, an analyte initiates the cross-opening of two DNA hairpins, yielding nicked double helices that are analogous to alternating copolymers. As an efficient amplification platform, HCR has been utilized for the sensitive detection of a wide variety of analytes, including nucleic acids, proteins, small molecules, and cells. In recent years, more complicated sets of monomers have been designed to develop nonlinear HCR, such as branched HCR and even dendritic systems, achieving quadratic and exponential growth mechanisms. In addition, HCR has attracted enormous attention in the fields of bioimaging and biomedicine, including applications in fluorescence in situ hybridization (FISH) imaging, live cell imaging, and targeted drug delivery. In this review, we introduce the fundamentals of HCR and examine the visualization and analysis techniques for HCR products in detail. The most recent HCR developments in biosensing, bioimaging, and biomedicine are subsequently discussed with selected examples. Finally, the review provides insight into the challenges and future perspectives of HCR.

In Situ Growth of Three-Dimensional Graphene Films for Signal-On Electrochemical Biosensing of Various Analytes.

In this work, an in situ growth protocol is introduced to fabricate three-dimensional graphene films (3D GFs) on gold substrates, which are successfully utilized as working electrode for electrochemical detection of nucleic acid (microRNA) and protein (lysozyme) based on a signal-on sensing mechanism. To realize the bridge between the gold substrate and graphene film, a monolayer of 4-aminothiophenol is self-assembled on the substrate, which is then served as connectors for the growth of 3D GFs on the gold substrate by the hydrothermal reduction (HR) technique. Moreover, given the excellent properties, such as enlarged surface area, strong binding strength between 3D GFs and gold substrate, and improved conductivity, the proposed 3D GF-fabricated gold substrate is readily employed to the construction of electrochemical biosensing platforms through introduction of magnetic nanoparticles (MNPs) as probe carriers. On the basis of the strand displacement reaction and specific binding between aptamer and its target, the developed biosensors achieve signal-on detection of microRNA-155 (miR-155) and lysozyme (Lyz) with high sensitivity and selectivity and further successfully applied to human serum assay. Overall, the proposed strategy for in situ growth of 3D GFs provides a powerful tool for a wide range of applications, which is not limited to electrochemical biosensors and can be extended to other areas, such as electrocatalysis and electronic energy-related systems.

Two-photon excited quantum dots with compact surface coatings of polymer ligands used as an upconversion luminescent probe for dopamine detection in biological fluids.

Water-soluble multidentate polymer coated CdTe quantum dots (QDs) were prepared via a stepwise addition of raw materials in a one-pot aqueous solution under ambient conditions. Just by adjusting the compositions of raw materials, different sized CdTe QDs were achieved within a short time. The as-prepared QDs showed compact surface coating (1.6-1.8 nm) of polymer ligands and photoluminescence (PL) emitted at 533-567 nm, as well as high colloidal/photo-stability and quantum yields (58-67%). Moreover, these QDs exhibited significant upconversion luminescence (UCL) upon excitation using an 800 nm femtosecond laser. Experimental results confirm that the UCL was ascribed to the two-photon assisted process via a virtual energy state. Then, the two-photon excited QDs were further developed as a novel UCL probe of dopamine (DA) due to self-assembled binding of DA molecules with QDs via non-covalent bonding. As a receptor, the DA attached onto the QD surface induced an electron transfer from QDs to DA, triggering UCL quenching of QDs. This UCL probe of DA presented a low limit of detection (ca. 5.4 nM), and high selectivity and sensitivity in the presence of potential interferences. In particular, it was favorably applied to the detection of DA in biological fluids, with quantitative recoveries (96.0-102.6%).

Hyperbranched Hybridization Chain Reaction for Triggered Signal Amplification and Concatenated Logic Circuits.

A hyper-branched hybridization chain reaction (HB-HCR) is presented herein, which consists of only six species that can metastably coexist until the introduction of an initiator DNA to trigger a cascade of hybridization events, leading to the self-sustained assembly of hyper-branched and nicked double-stranded DNA structures. The system can readily achieve ultrasensitive detection of target DNA. Moreover, the HB-HCR principle is successfully applied to construct three-input concatenated logic circuits with excellent specificity and extended to design a security-mimicking keypad lock system. Significantly, the HB-HCR-based keypad lock can alarm immediately if the "password" is incorrect. Overall, the proposed HB-HCR with high amplification efficiency is simple, homogeneous, fast, robust, and low-cost, and holds great promise in the development of biosensing, in the programmable assembly of DNA architectures, and in molecular logic operations.

A bimetallic peroxidase-mimicking nanozyme with antifouling property for construction of sensor array to identify phosphoproteins and diagnose cancers.

Protein phosphorylation is a significant post-translational modification that plays a decisive role in the occurrence and development of diseases. However, the rapid and accurate identification of phosphoproteins remains challenging. Herein, a high-throughput sensor array has been constructed based on a magnetic bimetallic nanozyme (Fe3O4@ZNP@UiO-66) for the identification and discrimination of phosphoproteins. Attributing to the formation of Fe-Zr bimetallic dual active centers, the as-prepared Fe3O4@ZNP@UiO-66 exhibits enhanced peroxidase-mimicking catalytic activity, which promotes the electron transfer from Zr center to Fe(II)/Fe(III). The catalytic activity of Fe3O4@ZNP@UiO-66 can be selectively inhibited by phosphoproteins due to the strong interaction between phosphate groups and Zr centers, as well as the ultra-robust antifouling capability of zwitterionic dopamine nanoparticle (ZNP). Considering the diverse binding affinities between various proteins with the nanozyme, the catalytic activity of Fe3O4@ZNP@UiO-66 can be changed to various degree, leading to the different absorption responses at 420 nm in the hydrogen peroxide (H2O2) - 2, 2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) system. By simply extracting different absorbance intensities at various time points, a sensor array based on reaction kinetics for the discrimination of phosphoproteins from other proteins is constructed through linear discriminant analysis (LDA). Besides, the quantitative determination of phosphoproteins and identification of protein mixtures have been realized. Further, based on the differential level of phosphoproteins in cells, the differentiation of cancer cells from normal cells can also be implemented by utilizing the proposed sensor array, showing great potential in disease diagnosis.

Dual-mode optical biosensor based on multi-functional DNA structures for detecting bioactive small molecules.

Semiconducting polymer dots and hemin-functionalized DNA nanoflowers with excellent peroxidase-like activity and high fluorescent brightness are prepared for fluorescent/colorimetric dual-mode sensing of dopamine and glutathione as low as nM and µM, respectively. This biosensor is readily applied to the analysis of complicated biological samples with high selectivity and accuracy, which opens up promising prospects in clinical applications.

NIR-driven photoelectrochemical-fluorescent dual-mode biosensor based on bipedal DNA walker for ultrasensitive detection of microRNA.

Optical biosensors have become powerful tools for bioanalysis, but most of them are limited by optic damage, autofluorescence, as well as poor penetration ability of ultraviolet (UV) and visible (Vis) light. Herein, a near-infrared light (NIR)-driven photoelectrochemical (PEC)-fluorescence (FL) dual-mode biosensor has been proposed for ultrasensitive detection of microRNA (miRNA) based on bipedal DNA walker with cascade amplification. Fueled by toehold-mediated strand displacement (TMSD), the bipedal DNA walker triggered by target miRNA-21 is formed through catalytic hairpin assembly (CHA), which can efficiently move along DNA tracks on CdS nanoparticles (CdS NPs)-modified fluorine doped tin oxide (FTO) electrode, resulting in the introduction of upconversion nanoparticles (UCNPs) on electrode surface. Under 980 nm laser irradiation, the UCNPs serve as the energy donor to emit UV/Vis light and excite CdS NPs to generate photocurrent for PEC detection, while the upconversion luminescence (UCL) at 803 nm is monitored for FL detection. This PEC-FL dual-mode biosensor has achieved the ultrasensitive and accurate analysis of miRNA-21 in human serum and different gynecological cancer cells. Overall, the proposed dual-mode biosensor can not only couple the inherent features of each single-mode biosensor but also provide mutual authentication of testing results, which opens up a new avenue for early diagnosis of miRNA-related diseases in clinic.

Ultrasensitive detection of mRNA extracted from cancerous cells achieved by DNA rotaxane-based cross-rolling circle amplification.

An ultrasensitive and highly selective method for polymerase chain reaction-free (PCR-free) messenger RNA (mRNA) expression profiling is developed through a novel cross-rolling circle amplification (C-RCA) process based on DNA-rotaxane nanostructures. Two species of DNA pseudorotaxane (DPR) superstructures (DPR-I and DPR-II) are assembled by threading a linear DNA rod through a double-stranded DNA (dsDNA) ring containing two single-stranded gaps. In this assay, cDNA that is specific for ß-actin (ACTB) mRNA is taken as a model analyte. Upon the introduction of the target cDNA, the cDNA and the biotin-modified primer are hybridized to the single-stranded regions of the DNA rod and the gap-ring, respectively. As a result, the DPR-I dethreads into free DNA macrocycle and a dumbbell-shaped DNA nanostructure. In the presence of DNA polymerase/dNTPs, two release-DNA on the DPR-I are replaced by polymerase with strand-displacement activity, which can act as the input of the DPR-II to trigger the dethreading of DPR-II and the RCA reaction, releasing another two specified release-DNA strands those in turn serve as the "mimic cDNA" for DPR-I. The C-RCA reaction then proceeds autonomously. To overcome the high background induced by hemin itself, the biotinylated rolling circle products are captured by streptavidin-coated MNPs, achieving a detection limit as low as 0.1 zmol cDNA. The assay also exhibits an excellent selectivity due to its unique DNA nanostructure fabricated through base pairing hybridization. The ACTB mRNA expression in mammary cancer cells (MCF-7) is successfully detected.

Recent Progress in Sensor Arrays: From Construction Principles of Sensing Elements to Applications.

The traditional sensors are designed based on the "lock-and-key" strategy with high selectivity and specificity for detecting specific analytes, which however are not suitable for detecting multiple analytes simultaneously. With the help of pattern recognition technologies, the sensor arrays excel in distinguishing subtle changes caused by multitarget analytes with similar structures in a complex system. To construct a sensor array, the multiple sensing elements are undoubtedly indispensable units that will selectively interact with targets to generate the unique "fingerprints" based on the distinct responses, enabling the identification among various analytes through pattern recognition methods. This comprehensive review mainly focuses on the construction strategies and principles of sensing elements, as well as the applications of sensor array for identification and detection of target analytes in a wide range of fields. Furthermore, the present challenges and further perspectives of sensor arrays are discussed in detail.

Functional Nucleic Acids-Engineered Bio-Barcode Nanoplatforms for Targeted Synergistic Therapy of Multidrug-Resistant Cancer.

Rational design of multifunctional nanomedicines has revolutionized the therapeutic efficacy of cancers. Herein, we have constructed the functional nucleic acids (FNAs)-engineered nanoplatforms based on the concept of a bio-barcode (BBC) for synergistic targeted therapy of multidrug-resistant (MDR) cancer. In this study, the platinum(IV) prodrug is synthesized to covalently link two kinds of FNAs at a rational ratio to fabricate three-dimensional BBC-like DNA nanoscaffolds, accompanied by the one-pot encapsulation of ZnO nanoparticles (NPs) through electrostatic interaction. The multivalent AS1411 aptamers equipped in ZnO@BBCs facilitate specific and efficient endocytosis into MDR human lung adenocarcinoma cells (A549/DDP). In response to the intracellular environment of A549/DDP cells, such as the lysosome-acidic pH and overexpressed GSH, the ZnO NPs are degraded into Zn2+ ions for generating reactive oxygen species (ROS), while the Pt(IV) prodrugs are reduced into Pt(II) active species by glutathione (GSH), followed by the release of therapeutic DNAzymes for chemotherapy and gene therapy. In particular, the designed system plays an important role in remodeling the intracellular environment to reverse cancer MDR. On the one hand, the depletion of GSH promotes the downregulation of glutathione peroxidase 4 (GPX4) for amplifying oxidative stress and increasing lipid peroxidation (LPO), resulting in the activation of ferroptosis. On the other hand, the silence of early growth response protein 1 (Egr-1) mRNA by Zn2+-dependent DNAzymes directly inhibits the proliferation and migration of MDR cells, which further suppresses the P-glycoprotein (P-gp)-mediated drug efflux. Thus, the proposed nanoplatforms show great promise for the development of versatile therapeutic tools and personalized nanomedicines for MDR cancers.