Etching of Ag nanoparticles triggered bidirectional regulation for electrochemiluminescence ratiometric immunoassay.

A highly efficient ratiometric electrochemiluminescence (ECL) immunoassay was explored by bidirectionally regulating the ECL intensity of two luminophors. The immunoassay was conducted in a split-type mode consisting of an ECL detection procedure and a sandwich immunoreaction. The ECL detection was executed using a dual-disk glassy carbon electrode modified with two potential-resolved luminophors (g-C3N4-Ag and Ru-MOF-Ag nanocomposites), and the sandwich immunoreaction using glucose oxidase (GOx)-modified SiO2 nanospheres as labels was carried out in a 96-well plate. The Ag nanoparticles (NPs) acted as bifunctional units both for triggering the resonance energy transfer (RET) with g-C3N4 and for accelerating the electron transfer rate of the Ru-MOF-Ag ECL reaction. When the H2O2 catalyzed by GOx in the 96-well plate was transferred to the dual-disk glass carbon electrode, the doped Ag NPs in the two luminophors could be etched, thus destroying the RET between C3N4 and the accelerated reaction to Ru-MOF, resulting in an opposite trend in the ECL signal outputted from the dual disks. Using the ratio of the two signals for quantification, the constructed immunosensor for a model target, i.e. myoglobin, exhibited a low detection limit of 4.7 × 10-14 g/mL. The ingenious combination of ECL ratiometry, bifunctional Ag NPs, and a split-type strategy effectively reduces environmental and human errors, offering a more precise and sensitive analysis for complex samples.

Spectroscopic Signature of the Carbon-Carbon Coupling Reaction between Carbon Monoxide and Nickel Carbide.

Spectroscopic characterization of ketenylidene complexes is of essential importance for understanding the structure-reactivity relationships of the catalytic sites. Here, we report a size-specific photoelectron velocity map imaging spectroscopic study of the reactions of carbon monoxide with nickel carbide. Quantum chemical calculations have been conducted to search for the energetically favorable isomers and to recognize the experimental spectra. The target products with the chemical formula of NiC(CO)n- (n = 3-5) are characterized to have an intriguing ketenylidene CCO unit. The evolution from NiC(CO)3- to NiC(CO)4- involves the breaking and formation of the Ni-C bond and the coordination conversion between the terminal and bridging carbonyls. Experimental and theoretical analyses reveal an efficient C-C bond formation process within the reactions of carbon monoxide and laser-vaporized nickel carbide. This work highlights the pivotal roles played by metal carbides in the C-C bond formation and also proposes new ideas for the design and chemical control of a broad class of complexes with unique physical and chemical properties.

H2O2-activated independently bidirectional regulation for a sensitive and accurate electrochemiluminescence ratiometric analysis.

Potential-resolved electrochemiluminescence (ECL) ratiometric analysis has become a research hotspot in bioassays by virtue of its good accuracy, versatility and specificity. Current ECL ratiometry mainly focuses on the competition for the co-reactant or quantitative analysis using a variable signal and a changeless signal; the disorganized change or small difference between the two signals may affect the accuracy and sensitivity of detection. In this study, we have developed a novel ECL ratiometric sensor based on the bidirectional regulation of two independent co-reaction systems by H2O2. H2O2 as a bidirectional moderator permits the ECL signals of the cathode and anode to independently change in opposite trends, which greatly enhances the organization and difference between the two signals. The ratio of the two signals is used to realize the quantitative analysis of myoglobin (MyO) with a good linear relationship between log(ECLcathode/ECLanode) and log CMyO in the range of 1.0 × 10-13 to 1.0 × 10-7 g mL-1. The detection limit is 4.0 × 10-14 g mL-1. Furthermore, it showed excellent performance in the determination of MyO in human serum samples. The proposed biosensor provides some developments for the sensitive and accurate detection of disease markers.

Dual-wavelength electrochemiluminescence ratiometry for hydrogen sulfide detection based on Cd2+-doped g-C3N4 nanosheets.

Herein, a novel and facile dual-wavelength ratiometric electrochemiluminescence-resonance energy transfer (ECL-RET) sensor for hydrogen sulfide (H2S) detection was constructed based on the interaction between S2- and Cd2+-doped g-C3N4 nanosheets (NSs). Cd2+-doped g-C3N4 NSs exhibited a strong ECL emission at 435 nm. In the presence of H2S, CdS was formed in situ on g-C3N4 NSs by the adsorption of S2- and Cd2+, generating another ECL emission at 515 nm. Furthermore, the overlapping of the absorption spectrum of the formed CdS and the ECL emission spectrum of g-C3N4 NSs led to a feasible RET, thus quenching the ECL intensity from g-C3N4 at 435 nm. Through an ECL decrease at 435 nm and an increase at 515 nm, a dual-wavelength ratiometric ECL-RET system for H2S was designed. The sensor exhibited a lower detection limit of 0.02 µM with a wide linear range of 0.05-100.0 µM. In addition, the applicability of the method was validated by plasma sample analysis with a linear range of 80.0-106.0%. We believe that such a proposal would provide new insight into advanced dual-wavelength ECL ratiometric assays.

Photogenerated Hole-Induced Chemical-Chemical Redox Cycling Strategy on a Direct Z-Scheme Bi2S3/Bi2MoO6 Heterostructure Photoelectrode: Toward an Ultrasensitive Photoelectrochemical Immunoassay.

To achieve high sensitivity for biomolecule detection in photoelectrochemical (PEC) bioanalysis, the ideal photoelectrode and ingenious signaling mechanism play crucial roles. Herein, the feasibility of the photogenerated hole-induced chemical-chemical redox cycling amplification strategy on a Z-scheme heterostructure photoelectrode was validated, and the strategy toward enhanced multiple signal amplification for advanced PEC immunoassay application was developed. Specifically, a direct Z-scheme Bi2S3/Bi2MoO6 heterostructure was synthesized via a classic hydrothermal method and served as a photoelectrode for the signal response. Under the illumination, the PEC chemical-chemical redox cycling (PECCC) among 4-aminophenol generated by the enzymatic catalysis from a sandwich immunoassay, ferrocene as a mediator, and tris (2-carboxyethyl) phosphine as a reducing agent was run on the Z-scheme Bi2S3/Bi2MoO6 heterostructure photoelectrode. Exemplified by interleukin-6 (IL-6) as the target, the applicability of the strategy was studied in a PEC immunoassay. Thanks to the multiple signal amplification originating from the high efficiency of the PECCC redox cycling system, the enzymatic amplification, and the fine performance of the Z-scheme Bi2S3/Bi2MoO6 heterostructure photoelectrode, the assay for IL-6 exhibits a very low detection limit of 2.0 × 10-14 g/mL with a linear range from 5.0 × 10-14 to 1.0 × 10-8 g/mL. This work first validates the feasibility of the PECCC redox cycling on the Z-scheme heterostructure photoelectrode and the good performance of the strategy in PEC bioanalysis. We envision that it would provide a new prospective for highly sensitive PEC bioanalysis on the basis of a Z-scheme heterostructure.

Liposome-assisted enzyme catalysis: toward signal amplification for sensitive split-type electrochemiluminescence immunoassay.

Developing an efficient signal amplification strategy is very important to improve the sensitivity of bioanalysis. In this paper, a liposome-assisted enzyme catalysis signal amplification strategy was developed for electrochemiluminescence (ECL) immunoassay of prostate specific antigen (PSA) in a split-type mode. The sandwich immunoreaction occurred in a 96-well plate, and glucose oxidase (GOx) encapsulated and antibody-modified liposomes were used as labels. The ECL detection was carried out using a rGO-Au NP modified glassy carbon electrode (GCE). The large amount of generated H2O2, i.e. the coreactant of the luminol system, and the excellent catalytic behavior of rGO-Au NPs greatly boosted the ECL signal, resulting in the signal amplification. The developed ECL immunosensor for detecting PSA achieved a wider linear range from 1.0 × 10-13 to 1.0 × 10-8 g mL-1 and a detection limit of 1.7 × 10-14 g mL-1. The application of the proposed strategy was demonstrated by analyzing PSA in human serum samples with recoveries from 89.0% to 113.0%, and relative standard deviations (RSDs) were less than 6.6%. This work provides a new horizon to expand the application of liposomes for ECL bioanalysis.

Recent progress of heterostructure-based photoelectrodes in photoelectrochemical biosensing: a mini review.

Photoelectrochemical (PEC) biosensing has received increasing attention due to its great potential in the analysis of biomarkers. The performance of a PEC biosensor depends largely on photosensitive materials. The photoactive materials with excellent properties are of great importance to realize advanced PEC bioassays. Recently, as a special class of nanocomposites, heterostructures consisting of different types of semiconductors with potential applications in PEC systems have witnessed the rapid development to improve the performance of PEC biosensors. In this review, the research progress on the promising heterostructures has been introduced and summarized, and the applications of such heterostructures in PEC bioassays are provided. The future development of heterostructures pertaining to PEC biosensing systems has also been briefly discussed.

Ru(NH3)63+/Ru(NH3)62+-Mediated Redox Cycling: Toward Enhanced Triple Signal Amplification for Photoelectrochemical Immunoassay.

Herein we report an effective Ru(NH3)63+/Ru(NH3)62+-mediated photoelectrochemical-chemical-chemical (PECCC) redox cycling amplification (RCA) strategy toward enhanced triple signal amplification for advanced split-type PEC immunoassay application. Specifically, alkaline phosphatase (ALP) label was confined via a sandwich immunorecognition to convert 4-aminophenyl phosphate to the signal reporter 4-aminophenol (AP), which was then directed to interact with Ru(NH3)62+ as a redox mediator and tris (2-carboxyethyl) phosphine (TCEP) as reducing agent in the detection buffer. Upon illumination, the system was then operated upon the oxidation of Ru(NH3)62+ by the photogenerated holes on the Bi2S3/BiVO4 photoelectrode, starting the chain reaction in which the Ru(NH3)62+ was regenerated by Ru(NH3)63+-enabled oxidization of AP to p-quinoneimine, which was simultaneously recovered by TCEP. Exemplified by interleukin-6 (IL-6) as the analyte, the Ru(NH3)63+/Ru(NH3)62+-mediated, AP-involved PECCC RCA coupled with ALP enzymatic amplification could achieve triple signal amplification toward the ultrasensitive PEC IL-6 immunoassay. This protocol can be extended as a general basis for other numerous targets of interest. Besides, we believe this work could offer a new perspective for the further exploration of advanced RCA-based PEC bioanalysis.

Reduced graphene oxide-gold nanoparticles-catalase-based dual signal amplification strategy in a spatial-resolved ratiometric electrochemiluminescence immunoassay.

A novel spatial-resolved electrochemiluminescent (ECL) ratiometry for cardiac troponin I (cTnI) analysis was developed using resonance energy transfer (RET) and a coreactant consumption strategy for signal amplification. Specifically, the spatial-resolved dual-disk glassy carbon electrodes were modified with CdS nanowires (CdS NWs) and luminol-gold nanoparticles (L-Au NPs) as potential-resolved ECL emitters, respectively. After stepwise immobilization of anti-cTnI and bovine serum albumin on the dual-disk electrodes, the CdS NWs-based electrode, with varied concentrations of cTnI, was used to provide a working signal, whereas the L-Au NPs-based electrode, with a fixed amount of cTnI, was employed to provide the reference signal. To efficiently amplify the working signal on the CdS NWs-based electrode, an anti-cTnI-reduced graphene oxide-gold nanoparticles-catalase probe (anti-cTnI-rGO-Au NPs-CAT) was loaded onto the electrode to form a sandwich immunocomplex. The RET from CdS NWs to Au NPs and the coreactant (i.e. H2O2) consumption by the CAT generate a significant ECL decrease on the CdS NWs-based electrode in the presence of cTnI. This novel and sensitive ratiometric detection mode for cTnI was achieved using the ratio values of the working signal of the CdS NWs-based electrode and the reference signal of the L-Au NPs-based electrode. The integration of RET and coreactant consumption strategy in the designed spatial-resolved ratiometric platform endows the immunosensor with a wide linear range of 5.0 × 10-13 - 1.0 × 10-7 g mL-1 and a low detection limit of 0.10 pg mL-1 for cTnI. Furthermore, the method exhibits high accuracy and sensitivity for cTnI determination in human serum samples.

Watch out for the special location of intraventricular silicone oil following an intraocular tamponade - a 10-year follow-up case report based on CT/MRI.

BACKGROUND: Intraventricular silicone oil is a relatively rare complication resulted from silicone oil tamponade to treat retinal detachment. It is occasionally reported in previous literature. To the best of our knowledge, the long-term longitudinal comparisons of silicone oil both in the brain and in the postoperative eyeball based on CT/MRI were lacking, and intraventricular silicone oil accumulation beside lesions has been reported rarely. CASE PRESENTATION: A 63-year-old male patient underwent an intraocular tamponade with silicone oil in June 2009. Eight CT examinations and 2 MRI examinations were acquired between 2011 and 2018.The changes of silicone oil in the brain in CT/MRI as below: Silicone oil initially migration to bilateral lateral ventricular anterior horn was found in November 2011, it was aslo found at right side of suprasellar cisterna, and there was no change in location 6 h later; Silicone oil at the anterior horn of right lateral ventricle disappeared but remained at left lateral ventricle and right side of suprasellar cisterna in July 2014, and there was no change in location in a short-term reexamination. It was found at the middle of left lateral ventricle (adjacent to the real cause) in march 2018, but disappeared 3 months later, while remained at anterior horn of left lateral ventricular and right side of suprasellar cisterna all the time. There was no change in location in the next 2 follow-up (September and October in 2018). The CT values of silicone oil distributed throughout the brain were dynamically changed with time. CONCLUSION: It is important to recognize intraventricular silicone oil in a particular location.More important is to discover "the real murderer", which is the main cause of symptoms in the vicinity of special location. Moreover, the migration of silicone oil between eyeball and brain may not be always in a single direction.

Photoelectrochemical-Chemical-Chemical Redox Cycling for Advanced Signal Amplification: Proof-of-Concept Toward Ultrasensitive Photoelectrochemical Bioanalysis.

Signal amplification is essential for ultrasensitive photoelectrochemical (PEC) bioanalysis. Exploration of the facile and efficient route for multiple signal amplification is highly appealing. Herein, we present the concept of photoelectrochemical-chemical-chemical (PECCC) redox cycling as an advanced signal amplification route and a proof-of-concept toward ultrasensitive PEC bioanalysis. The system operated upon the bridging between the enzymatic generation of signaling species ascorbic acid (AA) from a sandwich immunoassay and the PECCC redox cycling among the ferrocenecarboxylic acid as redox mediator, the AA, and the tris(2-carboxyethyl)phosphine as reducing agent at the Bi2S3/Bi2WO6 photoelectrode. Exemplified by myoglobin (Myo) as target, the proposed system achieved efficient regeneration of AA and thus signal amplification toward the ultrasensitive split-type PEC immunoassay. This work first exploited the PECCC redox cycling, and we believe it will attract more interest in the research of PEC bioassays on the basis of advanced redox cycling.

Immuno-Electrochemiluminescent Imaging of a Single Cell Based on Functional Nanoprobes of Heterogeneous Ru(bpy)32+@SiO2/Au Nanoparticles.

It is valuable to develop a sensing platform for not only detecting a tumor marker in body fluids but also measuring its expression at single cells. In the present study, a simple closed bipolar electrodes-based electrochemiluminescence (BPEs-ECL) imaging strategy was developed for visual immunoassay of prostate specific antigen (PSA) at single cells using functional nanoprobes of heterogeneous Ru(bpy)32+@SiO2/Au nanoparticles. Multiple-assisted ECL signal amplification strategy was introduced into the detection system on the basis of the synergetic amplifying effect of the anodic and cathodic amplification. On the basis of the synergetic amplifying effect, the detection limits of PSA by using photomultiplier tube and charge-coupled device (CCD) imaging are 3.0 and 31 pg/mL, respectively. The obtained immunosensor was employed to evaluate PSA levels in serum samples with a satisfying result. Moreover, the obtained functional nanoprobes were used to visually profile the PSA expression on the surface of single LNCaP cells (a kind of prostate cancer cells) based on a bare BPE. The results show that the functional nanoprobes-based ECL imaging immunoassay provides a promising visual platform for detecting tumor markers (proteins and cancer cells) and thus shows a high potential in cancer diagnosis.

Cathodic electrochemiluminescence behaviour of MoS2 quantum dots and its biosensing of microRNA-21.

The cathodic electrochemiluminescence (ECL) behaviour of nontoxic MoS2 quantum dots (QDs) was studied for the first time using potassium peroxydisulfate as the co-reactant. Ag-PAMAM NCs, serving as difunctional tags for quenching and enhancing ECL of MoS2-reduced graphene oxide composites, were introduced into the ECL detection system for signal amplification. By modulating the interparticle distance between MoS2 QDs and Ag-PAMAM NCs, the ECL quenching from resonance energy transfer and the ECL enhancement from surface plasma resonance were realized. Coupling the good ECL performance of MoS2 QDs with the excellent ECL quenching and enhancement effects of Ag-PAMAM NCs, a novel MoS2 QDs-based ECL biosensing platform for sensitive detection of microRNA-21 was achieved with a detection limit of 0.20 fmol L-1 (S/N = 3). This method was successfully applied to the determination of microRNA-21 in human serum samples with recoveries of 90.0-110.0%, suggesting great potential for its applications in biological and chemical analysis.

Phosphonate-Stabilized Titanium-Oxo Clusters with Ferrocene Photosensitizer: Structures, Photophysical and Photoelectrochemical Properties, and DFT/TDDFT Calculations.

The metal-to-core charge transfer (MCCT) transition in sensitized titanium-oxo clusters is an important process for photoinduced electron injection in photovoltaic conversion. This process resembles most closely the Type II photoinjection in dye-sensitized solar cells. Herein we report the synthesis and photophysical and photoelectrochemical (PEC) properties of the phosphonate-stabilized titanium-oxo clusters containing the ferrocenecarboxylate ligands. These ferrocene-containing clusters exhibit intense visible absorption extended up to 600 nm along with low optical band gaps of ∼2.2 eV. The low-energy transitions of these clusters were systematically investigated by UV-vis spectroscopy and DFT/TDDFT calculations. The combined experimental and computational studies suggest that the ferrocenecarboxylate-substituted titanium-oxo clusters form a donor-acceptor (D-A) system. The low-energy transition of these clusters primarily involves the MCCT from the iron center to TiO cluster core. The TiO core structure and phosphonate ligands both have great influence on the PEC properties of the clusters. This work provides valuable examples for the sensitized titanium-oxo clusters in which electron injection takes place via MCCT transition.

Single gold@silver nanoprobes for real-time tracing the entire autophagy process at single-cell level.

This article describes a multimodified core-shell gold@silver nanoprobe for real-time monitoring the entire autophagy process at single-cell level. Autophagy is vital for understanding the mechanisms of human pathologies, developing novel drugs, and exploring approaches for autophagy controlling. A major challenge for autophagy study lies in real-time monitoring. One solution might come from real-time detection of in situ superoxide radicals (O2(•-)), because it is the main regulator of autophagy. In this work, our proposed nanoprobes were etched by O2(•-) and gave a notable wavelength change in the plasmon resonance scattering spectra. Both the experimental and simulated results suggested the wavelength change rate correlated well with O2(•-) level. This response enabled its application in real-time in situ quantification of O2(•-) during autophagy course. More importantly, with the introduction of "relay probe" operation, two types of O2(•-)-regulating autophagy processes were successfully traced from the beginning to the end, and the possible mechanism was also proposed.

Aptamer-based detection and quantitative analysis of human immunoglobulin E in capillary electrophoresis with chemiluminescence detection.

A novel aptamer-based CE with chemiluminescence (CL) assay was developed for highly sensitive detection of human immunoglobulin E (IgE). The IgE aptamer was conjugated with gold nanoparticles (AuNPs) to form AuNPs-aptamer that could specifically recognize the IgE to produce an AuNPs-aptamer-IgE complex. The mixture of the AuNPs-aptamer-IgE complex and the unbounded AuNPs-aptamer could be effectively separated by CE and sensitively detected with luminol-H2 O2 CL system. By taking the advantage of the excellent catalytic behavior of AuNPs on luminol-H2 O2 CL system, the ultrasensitive detection of IgE was achieved. The detection limit of IgE is 7.6 fM (S/N = 3) with a linear range from 0.025 to 250 pM. Successful detection of IgE in human serum samples was demonstrated and the recoveries of 94.9-103.2% were obtained. The excellent assay features of the developed approach are its specificity, sensitivity, adaptability, and very small sample consumption. Our design provides a methodology model for determination of rare proteins in biological samples.

Dual-signal amplification strategy for ultrasensitive chemiluminescence detection of PDGF-BB in capillary electrophoresis.

Many efforts have been made toward the achievement of high sensitivity in capillary electrophoresis coupled with chemiluminescence detection (CE-CL). This work describes a novel dual-signal amplification strategy for highly specific and ultrasensitive CL detection of human platelet-derived growth factor-BB (PDGF-BB) using both aptamer and horseradish peroxidase (HRP) modified gold nanoparticles (HRP-AuNPs-aptamer) as nanoprobes in CE. Both AuNPs and HRP in the nanoprobes could amplify the CL signals in the luminol-H2 O2 CL system, owing to the excellent catalytic behavior of AuNPs and HRP in the CL system. Meanwhile, the high affinity of aptamer modified on the AuNPs allows detection with high specificity. As proof-of-concept, the proposed method was employed to quantify the concentration of PDGF-BB from 0.50 to 250 fm with a detection limit of 0.21 fm. The applicability of the assay was further demonstrated in the analysis of PDGF-BB in human serum samples with acceptable accuracy and reliability. The result of this study exhibits distinct advantages, such as high sensitivity, good specificity, simplicity, and very small sample consumption. The good performances of the proposed strategy provide a powerful avenue for ultrasensitive detection of rare proteins in biological sample, showing great promise in biochemical analysis.

Aptasensor based on tripetalous cadmium sulfide-graphene electrochemiluminescence for the detection of carcinoembryonic antigen.

A facile label-free electrochemiluminescence (ECL) aptasensor, based on the ECL of cadmium sulfide-graphene (CdS-GR) nanocomposites with peroxydisulfate as the coreactant, was designed for the detection of carcinoembryonic antigen (CEA). Tripetalous CdS-GR nanocomposites were synthesized through a simple onepot solvothermal method and immobilized on the glassy carbon electrode surface. L-Cystine (L-cys) could largely promote the electron transfer and enhance the ECL intensity. Gold nanoparticles (AuNPs) were assembled onto the L-cys film modified electrode for aptamer immobilization and ECL signal amplification. The aptamer modified with thiol was adsorbed onto the surface of the AuNPs through a Au-S bond. Upon hybridization of the aptamer with the target protein, the sequence could conjugate CEA to form a Y architecture. With CEA as a model analyte, the decreased ECL intensity is proportional to the CEA concentration in the range of 0.01-10.0 ng mL(-1) with a detection limit of 3.8 pg mL(-1) (S/N = 3). The prepared aptasensor was applied to the determination of CEA in human serum samples. The recoveries of CEA in the human serum samples were between 85.0% and 109.5%, and the RSD values were no more than 3.4%.

Sensitive determination of hemoglobin in human blood and serum by flow injection coupled with chemiluminescence detection.

A sensitive method to detect hemoglobin (Hb) by flow injection (FI) coupled with chemiluminescence (CL) detection was described, which based on Hb strong enhancing effect on weak luminol-hydrazine CL system in alkaline medium. Parameters affecting the CL detection conditions and FI-CL system were optimized. The effects of possible coexisting substances in human blood and serum of detection Hb were evaluated. Under the optimum conditions, the net CL intensity versus Hb concentration was linear in the range of 5.0 x 10(-9) - 6.0 x 10(-5) g x mL(-1) with the detection limit of 5.8 x 10(-10) g x mL(-1) (9.0 x 10(-12) mol x L(-1)). The relative standard deviations (RSDs) for 8 replicate determinations of 5.0 x 10(-7) and 3.0 x 10(-6) g x mL(-1) Hb were 1.6% and 1.5%, respectively. In addition, the recoveries of Hb in human blood and serum were carried out and varied from 83.0% to 101.0%. The proposed method has been successfully applied for the determination of Hb in healthy human blood and serum. The possible mechanism of Hb enhancing the weak CL emission of luminol-hydrazine system in NaOH solution was discussed by fluorescence spectrophotometer and UV-Vis spectrophotometer.

DNA-hybrid-gated multifunctional mesoporous silica nanocarriers for dual-targeted and microRNA-responsive controlled drug delivery.

The design of an ideal drug delivery system with targeted recognition and zero premature release, especially controlled and specific release that is triggered by an exclusive endogenous stimulus, is a great challenge. A traceable and aptamer-targeted drug nanocarrier has now been developed; the nanocarrier was obtained by capping mesoporous silica-coated quantum dots with a programmable DNA hybrid, and the drug release was controlled by microRNA. Once the nanocarriers had been delivered into HeLa cells by aptamer-mediated recognition and endocytosis, the overexpressed endogenous miR-21 served as an exclusive key to unlock the nanocarriers by competitive hybridization with the DNA hybrid, which led to a sustained lethality of the HeLa cells. If microRNA that is exclusively expressed in specific pathological cell was screened, a combination of chemotherapy and gene therapy should pave the way for a targeted and personalized treatment of human diseases.