Presented herein is a simple, robust, and label-free homogeneous electrochemical sensing platform constructed for the detection of protein kinase activity and inhibition by integration of carboxypeptidase Y (CPY)-assisted peptide cleavage reaction and vertically ordered mesoporous silica films (MSFs). In this sensing platform, the substrate peptide composed of kinase-specific recognized sequence and multiple positively charged arginine (R) residues was ingeniously designed. In the presence of protein kinase, the substrate peptide was phosphorylated and then immediately resisted CPY cleavage. The phosphorylated peptide could be effectively adsorbed on the negatively charged surface of MSFs modified indium–tin oxide (ITO) electrode (MSFs/ITO) by noncovalent electrostatic attraction. The adsorbed peptide was subsequently used as a hamper to prevent the diffusion of electroactive probe (FcMeOH) to the electrode surface through the vertically aligned nanopores, resulting in a detectable reduction of electrochemical signal. As demonstrated for the feasibility and universality of the sensing platform, both protein kinase A (PKA) and casein kinase II (CK2) were selected as the models, and the detection limits were determined to be 0.083 and 0.095 UmL–1, respectively. This sensing platform had the merits of simplicity, easy manipulation, and improved phosphorylation and cleavage efficiency, which benefited from homogeneous solution reactions without sophisticated modification or immobilization procedures. In addition, given the key role of inhibition and protein kinase activity detection in cell lysates, this proposed sensing platform showed great potential in kinase-related bioanalysis and clinical biomedicine.

Measuring the levels of Fe3+ in human body has attracted considerable attention for health monitoring as it plays an essential role in many physiological processes. In this work, we reported a selective fluorescent nanoprobe for Fe3+ detection in biological samples based on ultrabright N/P codoped carbon dots. By employing adenosine 5′-triphosphate (ATP) as the carbon, nitrogen, and phosphorus source, the N/P codoped carbon dots could be simply prepared through hydrothermal treatment. The obtained carbon dots exhibited high quantum yields up to 43.2%, as well as excellent photostability, low toxicity, and water solubility. Because of the Fe–O–P bonds formed between Fe3+ and the N/P codoped carbon dots, this nanoprobe showed high selectivity toward Fe3+ against various potential interfering substances in the presence of EDTA. The fluorescence quenching of as-fabricated carbon dots was observed with the increasing Fe3+ concentration, and the calibration curve displayed a wide linear region over the range of 1–150 μM with a detection limit of 0.33 μM. The satisfactory accuracy was further confirmed with the river samples and ferrous sulfate tablets, respectively. With the above outstanding properties, these N/P codoped carbon dots were successfully applied for direct detection of Fe3+ in biological samples including human blood serum and living cells. As compared to the most reported carbon dots-based Fe3+ sensors, this nanoprobe showed high fluorescence, good accuracy, and excellent selectivity, which presents the potential practical application for diagnosis of Fe3+ related disease.

Copper pollution has become a very serious problem in modern society with the increasing industrial emission and the acid mine drainage. Copper deficiency or excess copper accumulation in human and animal livers can bring both oxidative stress and severe disorders. Thus, the development of a simple and efficient strategy for Cu2+ ion detection in water and blood samples is very necessary and meaningful. In this study, a simple, fast, and sensitive fluorescence method was put forward to detect Cu2+ ions based on C5 DNA-templated gold nanoclusters (AuNCs) and Fenton-like reactions. Under aerobic conditions, ascorbic acid is not only involved in the reduction of Cu2+, but also reacts with O2 to produce H2O2. Then, hydroxyl radical (˙OH), yielded by H2O2 and Cu+, can seriously quench the fluorescence of AuNCs. Attributed to the unique Fenton-like reaction between ascorbic acid and the Cu2+ ions, high selectivity was achieved for Cu2+ ion monitoring using this nanosensor, and the practical applications of this nanosensor in real water and blood samples were realized.

Resveratrol (Res) has emerged as an extremely promising natural molecule due to its vast therapeutic prospects. However, the potential of the drug is immensely hindered by several limiting factors including poor water solubility, limited chemical stability and high metabolization. Herein we report a facile synthesis of a Res-loaded folate-terminated PEG-phospholipid coated reduced graphene oxide nanoassembly (FA-PEG-Lip@rGO/Res) by simply sonicating Res and rGO in FA-PEG linked liposome (FA-PEG-liposome) suspensions. The as-obtained FA-PEG-Lip@rGO/Res exhibits a nanoscale size (148 ± 7 nm), a negative surface potential (−23.6 mV), an excellent drug loading (69.5 ± 4.3%), a high drug entrapment efficiency (86.9 ± 5.6%), good monodispersity and controlled release. Additionally, the nanoassembly can protect Res from UV-light induced instability. Owing to the folate mediated targeted delivery, the robust FA-PEG-Lip@rGO/Res can deliver loaded Res to human MCF-7 breast cancer cells with high specificity and excellent efficiency. The cell toxicity viability shows that unloaded FA-PEG-Lip@rGO has no cytotoxicity, confirming its suitability as a drug vehicle. Furthermore, a systematic in vivo study shows that, under near-infrared (NIR) laser irradiation, FA-PEG-Lip@rGO/Res exhibits highly efficient combined chemotherapy and photothermal therapy to eradicate xenografted tumor with a single dose intratumoral (i.t.) injection. Thus, a facile, stable, biocompatible, and highly-effective Res delivery system has been developed, which may greatly advance the application of Res in biomedical research.

Metal–organic frameworks (MOFs) have spurred tremendous research interest in the fields of nanoscience and nanotechnology. However, exploring their biomedical applications is still a daunting challenge. In this work, we employed an acid-degradable MOF, zeolitic imidazolate framework-8 (ZIF-8), both as a self-sacrificial template to synthesize uniform size/morphology-controllable hollow mesoporous silica materials (HMSNs) and as a mesopore blocker for fabricating a pH-responsive HMSN-based drug delivery system. Starting from the ZIF-8 template, a layer of mesoporous silica is coated on ZIF-8 and subsequently the template was self-degraded under acidic conditions to obtain HMSNs. A series of monodisperse HMSNs ranging from ca. 80 nm to ca. 3000 nm with morphologies that give rare examples of cubic and dodecahedral morphologies has been prepared. It is demonstrated that the as-made HMSNs possess well-defined mesopores, huge cavities and good biocompatibility, which make them favourable for drug delivery. So, ZIF-8 was then grafted onto the HMSN to block the pore orifice for pH-responsive intracellular anticancer drug release. The results indicated that the ZIF-8-coated HMSN with encapsulated doxorubicin hydrochloride (DOX) was an efficient drug delivery vehicle in cancer therapy using pH-responsive release. This strategy sheds new light on the application of MOF materials and provides great potential for biomedical applications.

Here, we report a novel metal–organic framework-based nanocomposite with encapsulated Pd@Au nanoparticles and doxorubicin (DOX) for pH- and NIR-triggered synergistic chemo-photothermal treatment of cancer cells. In this work, Pd nanoparticles, which have uniform size and dispersibility, were first synthesized and used as a template to direct the covering of Au nanosheets. The obtained Au coated Pd (Pd@Au) nanoparticles have excellent dispersibility and photothermal conversion ability, which makes them a good photothermal nanomaterial. Subsequently, an acid-degradable metal–organic framework of ZIF-8 was employed to synchronously encapsulate Pd@Au nanoparticles and DOX to get a metal–organic framework-based nanocomposite (DOX/Pd@Au@ZIF-8). Under acid conditions (e.g. pH ∼5.0 in a lysosome), the ZIF-8 framework of the DOX/Pd@Au@ZIF-8 nanocomposite could be degraded, resulting in the release of encapsulated DOX. Moreover, the present Pd@Au nanoparticles can effectively convert NIR laser light (780 nm, 2.1 W cm−2) into heat, not only further promoting the release of DOX, but also realizing the synergistic chemo-photothermal treatment of cancer cells. The in vitro experiments showed that this nanocomposite system has an excellent synergistic treatment effect on SMMC-7721 cells, even at low concentrations (e.g. 20 μg mL−1). With the properties of synergistic chemo-photothermal treatment, we hope that such a nanocomposite system of DOX/Pd@Au@ZIF-8 could open the door to designing a significant multifunctional system for diverse applications in cancer treatment.

Here, we have reported a core/satellite-like multifunctional nanocarrier for pH- and NIR-triggered synergistic chemothermal therapy and tumor imaging. In this system, upconversion nanoparticles (UCNPs), which have an average diameter of 23 nm, were first synthesized by a classic high-temperature solvent method and subsequently used as the imaging cores to direct the coating of mesoporous silica shells. The obtained mesoporous silica coated core–shell nanoparticles (UCNP@mSiO2) have a uniform pore size (4.2 nm) and excellent DOX loading ability (85.3 μmol g−1 SiO2), which makes UCNP@mSiO2 a good carrier. In order to finally obtain this core/satellite-like system (DOX@UCNP@mSiO2–AuNRs), gold nanorods (AuNRs) with a positive charge of 15 mV were subsequently capped on the negatively charged DOX loaded UCNP@mSiO2 (−30 mV) via electrostatic interactions. Under low-pH conditions (e.g. pH 4.9), the charge of mesoporous silica changed to −10.8 mV, leading to the separation of AuNRs and the release of entrapped DOX. Moreover, the present AuNRs can effectively convert NIR light (780 nm) into heat, and the increased temperature is as high as 20 °C under the laser power density of 2.0 W cm−2. This study showed that this system has excellent imaging ability and synergistic chemothermal therapy effect. A versatile synergistic therapy system such as DOX@UCNP@mSiO2–AuNRs is expected to have wide biomedical applications and may be particularly useful for synergistic tumor therapy.

•A label-free fluorescence strategy has been proposed for monitoring enzymes involved in ligase-mediated DNA repair.•A smart and high-efficient dumbbell-shaped DNA was designed and employed to template DNA-CuNPs.•The detection of analyte in dilute cells extracts was investigated and showed excellent sensitivity.•The proposed strategy holds the potential for other DNA repair enzymes detection.DNA repair processes are responsible for maintaining genome stability. Ligase and polynucleotide kinase (PNK) have important roles in ligase-mediated DNA repair. The development of analytical methods to monitor these enzymes involved in DNA repair pathways is of great interest in biochemistry and biotechnology. In this work, we reported a new strategy for label-free monitoring PNK and ligase activity by using dumbbell-shaped DNA templated copper nanoparticles (CuNPs). In the presence of PNK and ligase, the dumbbell-shaped DNA probe (DP) was locked and could resist the digestion of exonucleases and then served as an efficient template for synthesizing fluorescent CuNPs. However, in the absence of ligase or PNK, the nicked DP could be digested by exonucleases and failed to template fluorescent CuNPs. Therefore, the fluorescence changes of CuNPs could be used to evaluate these enzymes activity. Under the optimal conditions, highly sensitive detection of ligase activity of about 1 U/mL and PNK activity down to 0.05 U/mL is achieved. To challenge the practical application capability of this strategy, the detection of analyte in dilute cells extracts was also investigated and showed similar linear relationships. In addition to ligase and PNK, this sensing strategy was also extended to the detection of phosphatase, which illustrates the versatility of this strategy.

As a star material in cancer theranostics, photoresponsive gold (Au) nanostructures may still have drawbacks, such as low thermal conductivity, irradiation-induced melting effect and high cost. To solve the problem, copper (Cu) with a much higher thermal conductivity and lower cost was introduced to generate a novel Cu–Au alloy nanostructure produced by a simple, gentle and one-pot synthetic method. Having the good qualities of both Cu and Au, the irregularly-shaped Cu–Au alloy nanostructures showed several advantages over traditional Au nanorods, including a broad and intense near-infrared (NIR) absorption band from 400 to 1100 nm, an excellent heating performance under laser irradiation at different wavelengths and even a notable photostability against melting. Then, via a simple conjugation of fluorophore-labeled aptamers on the Cu–Au alloy nanostructures, active targeting and signal output were simultaneously introduced, thus constructing a theranostic platform based on fluorophore-labeled, aptamer-coated Cu–Au alloy nanostructures. By using human leukemia CCRF-CEM cancer and Cy5-labeled aptamer Sgc8c (Cy5-Sgc8c) as the model, a selective fluorescence imaging and NIR photothermal therapy was successfully realized for both in vitro cancer cells and in vivo tumor tissues. It was revealed that Cy5-Sgc8c-coated Cu–Au alloy nanostructures were not only capable of robust target recognition and stable signal output for molecular imaging in complex biological systems, but also killed target cancer cells in mice with only five minutes of 980 nm irradiation. The platform was found to be simple, stable, biocompatible and highly effective, and shows great potential as a versatile tool for cancer theranostics.

Here, we have reported a straightforward and effective synthetic strategy for synthesis of aspect-ratios-controllable mesoporous silica nanorods with hollow structure (hMSR) and its application for transcription factor (TF)-responsive drug delivery intracellular. Templating by an acid-degradable nickel hydrazine nanorods (NHNT), we have first synthesized the hollow dense silica nanorods and then coated on a mesoporous silica layer. Subsequently, the dense silica layer was removed by the surface-protected etching method and the hollow structure of hMSR was finally formed. The aspect ratios of the hMSR can be conveniently controlled by regulating the aspect ratios of NHNT. Four different hMSR with aspect ratios of ca. 2.5, ca. 5.3, ca. 8.1, and ca. 9.0 has been obtained. It was demonstrated that the as-prepared hMSRs have good stability, high drug loading capacity, and fast cell uptake capability, which makes them to a potential nanocarrier for drug delivery. As the paradigm, hMSR with an aspect ratio of ca. 8.1 was then applied for TF-responsive intracellular anticancer drug controlled release by using a Ag+-stabilized molecular switch of triplex DNA (TDNA) as capping agents and probes for TFs recognition. In the presence of TF, the pores of hMSR can be unlocked by the TFs induced disassembly of TDNA, leading to the leakage of DOX. The research in vitro displayed that this system has a TFs-triggered DOX release, and the cytotoxicity in L02 normal cells was lower than that of HeLa cells. We hope that this developed hMSR-based system will promote the development of cancer therapy in related fields.Keywords: controllable aspect ratios; controlled release; hollow mesoporous silica nanorod; intracellular drug delivery; transcription factor (TFs)-responsive

The outstanding progress of nanoparticles-based delivery systems capable of releasing hypoglycemic drugs in response to glucose has dramatically changed the outlook of diabetes management. However, the developed glucose-responsive systems have not offered real-time monitoring capabilities for accurate quantifying hypoglycemic drugs released. In this study, we present a multifunctional delivery system that integrates both delivery and monitoring issues using glucose-triggered competitive binding scheme on alizarin complexone (ALC) functionalized mesoporous silica nanoparticles (MSN). In this system, ALC is modified on the surface of MSN as the signal reporter. Gluconated insulin (G-Ins) is then introduced onto MSN-ALC via benzene-1,4-diboronic acid (BA) mediated esterification reaction, where G-Ins not only blocks drugs inside the mesopores but also works as a hypoglycemic drug. In the absence of glucose, the sandwich-type boronate ester structure formed by BA binding to the diols of ALC and G-Ins remains intact, resulting in an fluorescence emission peak at 570 nm and blockage of pores. Following a competitive binding, the presence of glucose cause the dissociation of boronate ester between ALC and BA, which lead to the pores opening and disappearance of fluorescence. As proof of concept, rosiglitazone maleate (RSM), an insulin-sensitizing agent, was doped into the MSN to form a multifunctional MSN (RSM@MSN-ALC-BA-Ins), integrating with double-drugs loading, glucose-responsive performance, and real-time monitoring capability. It has been demonstrated that the glucose-responsive release behaviors of insulin and RSM in buffer or in human serum can be quantified in real-time through evaluating the changes of fluorescence signal. We believe that this developed multifunctional system can shed light on the invention of a new generation of smart nanoformulations for optical diagnosis, individualized treatment, and noninvasive monitoring of diabetes management.Keywords: alizarin complexone; competitive binding; glucose-responsive; mesoporous silica nanoparticles; monitoring drug release

Measuring pH in living cells is of great importance for better understanding cellular functions as well as providing pivotal assistance for early diagnosis of diseases. In this work, we report the first use of a novel kind of label-free carbon dots for intracellular ratiometric fluorescence pH sensing. By simple one-pot hydrothermal treatment of citric acid and basic fuchsin, the carbon dots showing dual emission bands at 475 and 545 nm under single-wavelength excitation were synthesized. It is demonstrated that the fluorescence intensities of the as-synthesized carbon dots at the two emissions are pH-sensitive simultaneously. The intensity ratio (I475 nm/I545 nm) is linear against pH values from 5.2 to 8.8 in buffer solution, affording the capability as ratiometric probes for intracellular pH sensing. It also displays that the carbon dots show excellent reversibility and photostability in pH measurements. With this nanoprobe, quantitative fluorescence imaging using the ratio of two emissions (I475 nm/I545 nm) for the detection of intracellular pH were successfully applied in HeLa cells. In contrast to most of the reported nanomaterials-based ratiometric pH sensors which rely on the attachment of additional dyes, these carbon-dots-based ratiometric probes are low in toxicity, easy to synthesize, and free from labels.

Herein, a simple, facile, and label-free electrochemiluminescence (ECL) aptasensor platform was constructed by integration of aptamer-gated systems and vertically ordered mesoporous silica films (MSFs) grown in suit of indium–tin oxide (ITO) electrode. In this aptasensor platform, aptamer could be effectively adsorbed on the surface of aminated MSFs by noncovalent electrostatic attraction and then employed as an ideal gate material to control the blocking and releasing of luminescence reagents (Ru(bipy)32+) entrapped within the pores of MSFs. In the presence of target, the specific aptamer-target binding could trigger the uncapping the pores, releasing the Ru(bipy)32+ with detectable reduced of ECL signal. The feasibility and universality of this design was validated by employing three aptamers that bind to lysozyme, adenosine, and K+ as gate materials, and the detection limits were determined to be 0.06 nM, 0.75 nM, and 0.5 μM, respectively. This ECL aptasensor, based on the simple competitive procedure, was simple design, undemanding, and fast in operation. In addition, no other chemical modification of the aptamer was required, suggesting that this ECL aptasensor could be applied to many other target detections just by altering the aptamer sequence.

DNA-based activatable theranostic nanoprobes are still unmet for in vivo applications. Here, by utilizing the “induced-fit effect”, a smart split aptamer-based activatable theranostic probe (SATP) was first designed as “nanodoctor” for cancer-activated in vivo imaging and in situ drug release. The SATP assembled with quenched fluorescence and stable drug loading in its free state. Once binding to target proteins on cell surface, the SATP disassembled due to recognition-triggered reassembly of split aptamers with activated signals and freed drugs. As proof of concept, split Sgc8c against CEM cancer was used for theranostic studies. Benefiting from the design without blocking aptamer sequence, the SATP maintained an excellent recognition ability similar to intact Sgc8c. An “incubate-and-detect” assay showed that the SATP could significantly lower background and improve signal-to-background ratio (∼4.8 times of “always on” probes), thus affording high sensitivity for CEM cell analysis with 46 cells detected. Also, its high selectivity to target cells was demonstrated in analyzing mixed cell samples and serum samples. Then, using doxorubicin as a model, highly specific drug delivery and cell killing was realized with minimized toxicity to nontarget cells. Moreover, in vivo and ex vivo investigations also revealed that the SATP was specifically activated by CEM tumors inside mice. Especially, contrast-enhanced imaging was achieved in as short as 5 min, thus, laying a foundation for rapid diagnosis and timely therapy. As a biocompatible and target-activatable strategy, the SATP may be widely applied in cancer theranostics.

We present here a pH-responsive activatable aptamer probe for targeted cancer imaging based on i-motif-driven conformation alteration. This pH-responsive activatable aptamer probe is composed of two single-stranded DNA. One was used for target recognition, containing a central, target specific aptamer sequence at the 3'-end and an extension sequence at the 5'-end with 5-carboxytetramethylrhodamine (TAMRA) label (denoted as strand A). The other (strand I), being competent to work on the formation of i-motif structure, contained four stretches of the cytosine (C) rich domain and was labeled with a Black Hole Quencher 2 (BHQ2) at the 3'-end. At neutral or slightly alkaline pH, strand I was hybridized to the extension sequence of strand A to form a double-stranded DNA probe, termed i-motif-based activatable aptamer probe (I-AAP). Because of proximityinduced energy transfer, the I-AAP was in a “signal off” state. The slightly acidic pH enforced the strand I to form an intramolecular i-motif and then initiated the dehybridization of I-AAP, leading to fluorescence readout in the target recognition. As a demonstration, AS1411 aptamer was used for MCF-7 cells imaging. It was displayed that the I-AAP could be carried out for target cancer cells imaging after being activated in slightly acidic environment. The applicability of I-AAP for tumor tissues imaging has been also investigated by using the isolated MCF-7 tumor tissues. These results implied the I-AAP strategy is promising as a novel approach for cancer imaging.

•A simple, rapid and mild strategy for synthesis of DNA-templated gold nanoclusters (AuNCs) was developed.•This process could be completed within 5 min after the reaction beginning under ambient conditions.•C5 DNA was found as the best template for the formation of fluorescent AuNCs in this system.•This C5-AuNCs could be applied to detecting Hg2+ ions with excellent selectivity.In this work, we developed a simple, rapid and mild strategy for synthesis of DNA-templated fluorescent gold nanoclusters (AuNCs) through association of gold ions to DNA templates and reduction with 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES). After systematical investigation on the formation of fluorescent AuNCs by using different DNA templates, C5 DNA was found as the best template for the formation of fluorescent AuNCs in this system. This process could be completed within 5 min after the reaction beginning under ambient conditions. The prepared C5-AuNCs displayed good blue emission and photostability. Furthermore, this C5-AuNCs could be applied to detecting Hg2+ ions specifically based on the specific and strong interaction between Hg2+ and Au+. The C5-AuNCs provided excellent selectivity for Hg2+ ions over other metal ions, and also high sensitivity, with a detection limit of 50 nM. As biocompatible, environmentally-friendly, and synthesis-rapid, this C5-AuNCs probe appears to be promising candidate for biochemical sensing via simple modification of template DNA.In this work, we developed a simple, rapid and mild strategy for synthesis of DNA-templated fluorescent gold nanoclusters (AuNCs) through association of gold ions to DNA templates and reduction with HEPES. This process could be completed within 5 min after the reaction beginning. Then, this blue fluorescence-emissive DNA-AuNCs was employed as a label-free probe for Hg2+ ions rapid detection based on Hg2+ induced fluorescence quenching.

In this paper, we report the assembly of reduced graphene oxide (RGO) and mesoporous silica grafted with alkyl chains (MSN-C18) to develop a new class of drug carriers which are able to deliver the loaded drug molecules into living cells upon exposure to near-infrared (NIR) light. This novel drug carrier consists of a structure formed by the noncovalent interaction of RGO caps and alkyl chains on the surface of MSN-C18. The capping of RGO sheets on mesoporous silica effectively blocks the pore mouths in the absence of NIR light. Conversely, and very importantly, the photothermal heating effect of RGO leads to a rapid increase in the local temperature upon exposure to NIR light, resulting in the weakening of the RGO sheet/alkyl chain noncovalent interaction. The RGO sheets will then be removed from the MSN surface, and the pores are uncapped. This uncapping mechanism makes it possible to release the loaded drug molecules upon irradiation with NIR light. In the present study, such a noncovalent assembly was examined by the use of doxorubicin as a model drug for NIR light-responsive intracellular controlled release studies. We believe that this noncovalent assembly will prove to be a promising drug delivery system for cancer therapy in the near future.

Owing to the over-expressed level in pheochromocytoma cells, dopamine (DA) provides a unique opportunity to design drug delivery systems for pheochromocytoma treatment. Herein, we developed a DA responsive delivery system for the treatment of pheochromocytoma cells based on mesoporous silica nanoparticles (MSNs) capped with DNA-templated silver nanoparticles (AgNPs). In this system, cytimidine-rich DNA grafted on the MSN was employed as the template to in situ drive the synthesis of AgNPs. The as-formed AgNPs were bound to the contour of DNA and blocked the pores to form the AgNPs capped MSNs (MSN@AgNPs). In the presence of DA, the capped AgNPs would break away from the surface of MSNs due to the reactivity of DA with AgNPs through the formation of Ag–catechol bonds, giving rise to the uncapped pores. Doxorubicin (DOX), as a model drug, was used to form DOX-loaded MSN@AgNPs (DOX@MSN@AgNPs) and then to assess the drug release behaviors from the DA-responsive delivery system. The in vitro studies showed that the DOX@MSN@AgNPs have a higher cytotoxicity to rat pheochromocytoma cell lines (PC-12 cells) when compared to human cervical cancer cell lines (HeLa cells). With these excellent features, we believe that this DA-triggered drug delivery system should promote the development of therapy in pheochromocytoma.

Redox-responsive degradable honeycomb manganese oxide (hMnO2) nanostructures consisting of some lamellar MnO2 platelets were established as a new class of drug carriers for intracellular glutathione-triggered drug release.

Here we present a novel large Stokes shifting NIR fluorescent nanomicelle through the encapsulation of a quantum dot/methylene blue FRET pair, which is employed as an excellent contrast reagent for NIR fluorescence bioimaging.

A sensitive turn-on fluorescent sensor based on single-layer MnO2 nanosheet-quenched fluorescent carbon quantum dots has been developed for rapid and selective sensing of glutathione in aqueous solutions, as well as in living cells.

Biomineralized fluorescent metal nanoparticles have attracted considerable interest in many fields by virtue of their excellent properties in synthesis and application. Poly(thymine)-templated fluorescent copper nanoparticles (T-CuNPs) as a promising nanomaterial has been exploited by us recently and displays great potential for signal transducing in biochemical analysis. However, the application of T-CuNPs is rare and still at an early stage. Here, a new fluorescent analytical strategy has been developed for H2O2 and oxidase-based biosensing by exploiting T-CuNPs as an effective signal indicator. The mechanism is mainly based on the poly(thymine) length-dependent formation of T-CuNPs and the probe’s oxidative cleavage. In this assay, the probe T40 can effectively template the formation of T-CuNPs by a fast in situ manner in the absence of H2O2, with high fluorescent signal, while the probe is cleaved into short-oligonucleotide fragments by hydroxyl radical (·OH) which is formed from the Fenton reaction in the presence of H2O2, leading to the decline of fluorescence intensity. By taking advantage of H2O2 as a mediator, this strategy is further exploited for oxidase-based biosensing. As the proof-of-concept, glucose in human serum has been chosen as the model system and has been detected, and its practical applicability has been investigated by assay of real clinical blood samples. Results demonstrate that the proposed strategy has not only good detection capability but also eminent detection performance, such as simplicity and low-cost, holding great potential for constructing effective sensors for biochemical and clinical applications.

Colorimetric analysis is promising in developing facile, fast, and point-of-care cancer diagnosis techniques, but the existing colorimetric cancer cell assays remain problematic because of dissatisfactory sensitivity as well as complex probe design or synthesis. To solve the problem, we here present a novel colorimetric analytical strategy based on iodide-responsive Cu–Au nanoparticles (Cu–Au NPs) combined with the iodide-catalyzed H2O2–TMB (3,3,5,5-tetramethylbenzidine) reaction system. In this strategy, bimetallic Cu–Au NPs prepared with an irregular shape and a diameter of ∼15 nm could chemically absorb iodide, thus indirectly inducing colorimetric signal variation of the H2O2–TMB system. By further utilizing its property of easy biomolecule modification, a versatile colorimetric platform was constructed for detection of any target that could cause the change of Cu–Au NPs concentration via molecular recognition. As proof of concept, an analysis of human leukemia CCRF-CEM cells was performed using aptamer Sgc8c-modified Cu–Au NPs as the colorimetric probe. Results showed that Sgc8c-modified Cu–Au NPs successfully achieved a simple, label-free, cost-effective, visualized, selective, and ultrasensitive detection of cancer cells with a linear range from 50 to 500 cells/mL and a detection limit of 5 cells in 100 μL of binding buffer. Moreover, feasibility was demonstrated for cancer cell analysis in diluted serum samples. The iodide-responsive Cu–Au NP-based colorimetric strategy might not only afford a new design pattern for developing cancer cell assays but also greatly extend the application of the iodide-catalyzed colorimetric system.

Staphylococcus aureus (S. aureus) is an important human pathogen that causes several diseases ranging from superficial skin infections to life-threatening diseases. Here, a method combining positive dielectrophoresis (pDEP) driven on-line enrichment and aptamer-fluorescent silica nanoparticle label has been developed for the rapid and sensitive detection of S. aureus in microfluidic channels. An aptamer, having high affinity to S. aureus, is used as the molecular recognition tool and immobilized onto chloropropyl functionalized fluorescent silica nanoparticles through a click chemistry approach to obtain S. aureus aptamer–nanoparticle bioconjugates (AptS.aureus/FNPs). The pDEP driven on-line enrichment technology was used for accumulating the AptS.aureus/FNP labeled S. aureus. After incubating with S. aureus, the mixture of AptS.aureus/FNP labeled S. aureus and AptS.aureus/FNPs was directly introduced into the pDEP-based microfluidic system. By applying an AC voltage in a pDEP frequency region, the AptS.aureus/FNP labelled S. aureus moved to the electrodes and accumulated in the electrode gap, while the free AptS.aureus/FNPs flowed away. The signal that came from the AptS.aureus/FNP labelled S. aureus in the focused detection areas was then detected. Profiting from the specificity of aptamer, signal amplification of FNP label and pDEP on-line enrichment, this assay can detect as low as 93 and 270 cfu mL−1S. aureus in deionized water and spiked water samples, respectively, with higher sensitivities than our previously reported AptS.aureus/FNP based flow cytometry. Moreover, without the need for separation and washing steps usually required for FNP label involved bioassays, the total assay time including sample pretreatment was within 2 h.

This paper proposed a novel and reversible molecule-gated system consisting of mesoporous silica nanoparticles (MSN) functionalized on the pore outlets with a G-rich quadruplex DNA (GQDNA). In this system, K+-stabilized GQDNA as a molecular switch was grafted onto the MSN surface through the covalent cross-linking approach. In the absence of silver ion (Ag+), GQDNA could fold into a quadruplex structure through π–π stacking between G–G pairs mediated by potassium ions (K+), thus blocking the pore outlets and inhibiting the release of entrapped guest molecules. In the presence of Ag+, the Ag+ can interact with G bases, leading to the unfolded GQDNA and subsequently opened pores. Interestingly, the opened pore mouths can be closed again by introducing glutathione (GSH) molecules, which can bind competitively with Ag+ ions by the thiols to result in the conformation transition of DNA from unfolded structures to quadruplex structures. By the simple conformational changes of GQDNA gatekeepers, the molecular gate can switch reversibly by the alternate addition of Ag+ ions and GSH molecules. As a proof-of-concept, Ru(bipy)32+, a strong fluorescence dye molecule, was loaded into GQDNA grafted MSN (MSN-Ru-GQDNA). The result showed that the MSN-Ru-GQDNA has a highly reversible ability to open/close pores which was proved by the released percentage of Ru(bipy)32+. With these excellent features, the release of Ru(bipy)32+ can be easily controlled at will. We believed that further developments of this reversible molecule-gated system will provide a promising nanodevice for on-demand molecular transport.

•A new signal-on electrochemical biosensing platform was developed.•Target binding-induced strand displacement and triple-helix forming was employed.•Triple-helix structure can be altered by adjusting pH without heating to 95 °C.•ATP and Tmb are used as model targets for the biosensing platform.Owing to its diversified structures, high affinity, and specificity for binding a wide range of non-nucleic acid targets, aptamer is a useful molecular recognition tool for the design of various biosensors. Herein, we report a new signal-on electrochemical biosensing platform which is based on an aptamer/target binding-induced strand displacement and triple-helix forming. The biosensing platform is composed of a signal transduction probe (STP) modified with a methylene blue (MB) and a sulfhydryl group, a triplex-forming oligonucleotides probe (TFO) and a target specific aptamer probe (Apt). Through hybridization with the TFO probe and the Apt probe, the self-assembled STP on Au electrode via Au–S bonding keeps its rigid structure. The MB on the STP is distal to the Au electrode surface. It is eT off state. Target binding releases the Apt probe and liberates the end of the MB tagged STP to fold back and form a triplex-helix structure with TFO (STP/TFO/STP), allowing MB to approach the Au electrode surface and generating measurable electrochemical signals (eT ON). As test for the feasibility and universality of this signal-on electrochemical biosensing platform, two aptamers which bind to adenosine triphosphate (ATP) and human α-thrombin (Tmb), respectively, are selected as models. The detection limit of ATP was 7.2 nM, whereas the detection limit of Tmb was 0.86 nM.

Despite the remarkable progress in the construction of nanostructures for drug delivery in cancer therapy, multifunctional nanoplatforms with synergistic advantages over any single-model nanostructures are still encouraging. Herein, a dual pH- and near-infrared (NIR)-responsive nanotherapeutic system for the chemothermal treatment of cancer cells was achieved by using adenine DNA coated gold nanorod vehicles (poly(A)/AuNR). The poly(A)/AuNRs were prepared by self-assembling thiolated poly(A) on the surface of the AuNRs via Au–S bonding. In this system, the poly(A) provided the ability to load coralyne, a model chemotherapeutic drug, through adenine–coralyne–adenine specific binding. Under low-pH or high-temperature conditions, adenine–coralyne–adenine would be unstable, leading to the stimuli-responsive release of coralyne for cancer chemotherapy. The AuNRs showed a high efficiency for the conversion of NIR light into heat, providing the fundamental basis of hyperthermal cancer therapy, and also promoting the triggered release of coralyne from poly(A) upon NIR irradiation. The characteristics of the poly(A)/AuNRs have been investigated by using TEM and UV-vis spectroscopy. It was shown that about 160 copies of poly(A) could be assembled on one AuNR prepared with the dimensions of about 30 nm in length and 10 nm in width, and each poly(A)/AuNR could load about 2500 coralyne molecules. The in vitro studies using human hepatoma SMMC-7721 cells demonstrated that the coralyne loaded poly(A)/AuNRs could be endocytosed and demonstrated an efficient operation in a cellular acidic environment and NIR irradiation, leading to significant cytotoxicity through the excellent chemothermal synergistic effects. We believe that this developed multimode nanostructure will provide potential applications for cancer therapy.

Despite remarkable progress in the construction of functional mesoporous silica nanoparticles (MSNs) for cancer therapy, a multifunctional system with synergistic advantages over any single model remains encouraging. The objective of the present study was to develop a novel, simple and powerful nanotherapeutic system for the pH- and near-infrared (NIR)-responsive chemothermal treatment of cancer cells by co-loading coralyne and indocyanine green (ICG) into the adenine DNA (poly(A))-functionalized MSN. Coralyne, a type of planar alkaloid for cancer chemotherapy, can not only be loaded into the pores of MSN, but can also bind poly(A) and trigger the formation of non-Watson–Crick secondary structures, resulting in pore capping by the cooperative binding of poly(A) strands. Under low-pH or high-temperature conditions, non-Watson–Crick secondary structures were unstable, leading to the dehybridization of the cooperative binding structure and open-gate state. ICG, another cargo co-loaded into MSN, showed high efficiency for the conversion of NIR light into heat, which could provide the fundamental basis of hyperthermal therapy and promote pore opening upon NIR irradiation. In vitro studies using human hepatoma (HepG-2) cells demonstrated that this system could perform well in cellular acidic environment and under NIR irradiation, leading to a significant efficiency in controlled drug release and chemothermal cancer treatment. We believe that with these excellent features it should become a favorable nanoplatform for biomedical applications.

We propose a novel template-assisted strategy to prepare nanometer-sized manganese oxide (nano-MnO2) by self-assembly of some MnO2 platelets and demonstrate its application as a new class of biosensing platform for probing DNA hybridization and aptamer–target interaction in a homogeneous solution.

Here we exploit dsDNA-specific fluorescent copper nanoparticles (CuNPs) as a “green” nano-dye for polymerization-mediated biochemical analysis. Good feasibility and universality are demonstrated through detecting three model targets (polymerase, mercury ion and nucleic acid).

Due to its importance to develop strategies for copper(II) (Cu2+) detection, we here report a visual and portable strategy for Cu2+ detection based on designing and using a strip-like hydrogel. The hydrogel is functionalized through caging poly(thymine) as probes, which can effectively template the formation of fluorescent copper nanoparticles (CuNPs) in the presence of the reductant (ascorbate) and Cu2+. On the hydrogel’s surface, uniform wells of microliter volume (microwells) are printed for sample-injection. When the injected sample is stained by Cu2+, fluorescent CuNPs will be in situ templated by poly T in the hydrogel. With ultraviolet (UV) irradiation, the red fluorescence of CuNPs can be observed by naked-eye and recorded by a common camera without complicated instruments. Thus, the strategy integrates sample-injection, reaction and indication with fast signal response, providing an add-and-read manner for visual and portable detection of Cu2+, as well as a strip-like strategy. Detection ability with a detectable minimum concentration of 20 μM and practically applicable properties have been demonstrated, such as resistance to environmental interference and good constancy, indicating that the strategy holds great potential and significance for popular detection of Cu2+, especially in remote regions. We believe that the strip-like hydrogel-based methodology is also applicable to other targets by virtue of altering probes.

Because of the intrinsic importance of nucleic acid as biotargets, the simple and sensitive detection of nucleic acid is very essential for biological studies and medical diagnostics. Herein, a new strategy for enzyme-free nucleic acid amplified detection has been opened up by combining the signal-amplification capability of target-catalyzed dynamic assembly with the spatially sensitive fluorescent signal of the pyrene excimer. In this strategy, three metastable pyrene-labeled hairpin DNA probes were designed as assembly components, which were kinetically handicapped from cross-opening in the absence of the target DNA. However, in the presence of the target, the dynamic assembly of branched junctions was circularly catalyzed and accompanied by the switching of the pyrene excimer which emits at ∼488 nm. Thus, the target DNA could be detected by this simple mix-and-detect amplification method, without expensive and perishable protein enzymes. A good detection capability exhibited with a detectable minimum target concentration of 10 pM, which was comparable to or even better than some reported enzyme-dependent amplification methods, and the potential for the target detection from complex fluids was verified. In addition, as a novel transformation of dynamic DNA assembly technology into enzyme-free signal-amplification analytical application, we infer that the proposed strategy will hold promising potential for application in a wider range of fields, including aptamer-based non-nucleic acid target sensing, biomedicine, and bioimaging.

Activatable aptamer probes (AAPs) have emerged as a promising strategy in cancer diagnostics, but existing AAPs remain problematic due to complex design and synthesis, instability in biofluids, or lack of versatility for both in vitro and in vivo applications. Herein, we proposed a novel AAP strategy for cancer cell probing based on fluorophore-labeled aptamer/single-walled carbon nanotube (F-apt/SWNT) ensembles. Through π-stacking interactions and proximity-induced energy transfer, F-apt/SWNT with quenched fluorescence spontaneously formed in its free state and realized signal activation upon targeting surface receptors of living cells. As a demonstration, Sgc8c aptamer was used for in vitro analysis and in vivo imaging of CCRF-CEM cancer cells. It was found that self-assembled Cy5-Sgc8c/SWNT held robust stability for biological applications, including good dispersity in different media and ultralow fluorescence background persistent for 2 h in serum. Flow cytometry assays revealed that Cy5-Sgc8c/SWNT was specifically activated by target cells with dramatic fluorescence elevation and showed improved sensitivity with as low as 12 CCRF-CEM cells detected in mixed samples containing ∼100 000 nontarget cells. In vivo studies confirmed that specifically activated fluorescence was imaged in CCRF-CEM tumors, and compared to “always on” probes, Cy5-Sgc8c/SWNT greatly reduced background signals, thus resulting in contrast-enhanced imaging. The general applicability of the strategy was also testified by detecting Ramos cells with aptamer TD05. It was implied that F-apt/SWNT ensembles hold great potential as a simple, stable, sensitive, specific, and versatile activatable platform for both in vitro cancer cell detection and in vivo cancer imaging.

•A nuclease-resistant and efficacious LNA/DNA chimeric aptamer probe was developed.•The combined use of LNA and 3′-3′-T exhibited a synergistic effect.•The optimized probe showed ∼10 times increased half-life for target cells in serum.•The in vivo tumor imaging window was extended from <150 min to >600 min.As promising molecular probes for in vivo tumor imaging, aptamers without modification remain problematic due to insufficient serum stability and unabiding imaging window. To address this problem, a novel locked nucleic acid (LNA)/DNA chimeric aptamer probe was developed through proper LNA incorporation and supplemented 3′-3′-thymidine (3′-3′-T) capping. TD05, a DNA aptamer against lymphoma Ramos cells, being used as the model, a series of modification strategies were designed and optimized with different positions, numbers and combinations. It was revealed that the combined use of LNA and 3′-3′-T had a synergistic effect, and with the increase of LNA substitution in stem region, the serum stability of TD05 was gradually enhanced while its affinity and specificity were perfectly maintained to Ramos cells. Particularly, TD05.6 with 7-base pair-LNA substitution exhibited the significantly elevated detection stability half-life from ∼0.5 h of TD05 to 5–6 h of TD05.6 for target cells in serum. Moreover, a much slower clearance rate in tumor-bearing mice was also observed for TD05.6, thus leading to the greatly extended tumor imaging window from <150 min of TD05 to >600 min of TD05.6. This strategy might be of great potentials to generate more aptamer probes that are stable and nuclease-resistant for tumor diagnosis in real biological systems.

A novel label-free tailed hairpin-shaped activatable aptamer probe (THAAP) was developed by rationally integrating an aptamer and a split G-quadruplex into one sequence. Based on target recognition-triggered in situ catalysis of split DNAzyme, the THAAP strategy achieved a simple, fast, washing-free, specific and quantitative colorimetric assay of human leukemic CCRF-CEM cells.

An aptamer is a useful molecular recognition tool for the design of various biosensors owing to their diversified structures, good biocompatibility, high affinity, and specificity for binding a wide range of non-nucleic acid targets, from small molecules to whole cells. Herein, we developed a signal on aptamer-based electrochemical sensing platform by taking advantage of a triple-helix molecular switch. In this sensing platform, two tailored DNA probes were involved for constructing a triple-helix molecular switch. One was a label-free target specific aptamer sequence (Apt) flanked by two arm segments, called as a recognition probe. The other, serving as a signal transduction probe (STP), was designed as a hairpin-shaped structure and labeled with methylene blue (MB) and a sulfhydryl group at the 3′ and 5′-end, respectively. The target specific Apt contained triple-helix DNA (Apt–THDNA) was formed by binding two arm segments of the Apt with the loop sequence of STP, and then self-assembled onto the gold electrode via Au–S bonding. Due to the “open” configuration of STP in the Apt–THDNA, the methylene blue modified on the STP was far away from the electrode. It was eT OFF state. Formation of an aptamer/target complex disassembled the Apt–THDNA and retained the STP section on the gold electrode. Subsequently, the retained STP on the gold electrode could form a hairpin-shaped configuration, mediating the methylene blue approach onto the gold electrode surface to generate redox current. It was eT on state. The developed facile signal on aptamer-based electrochemical sensing platform using a triple-helix molecular switch showed a linear response to the concentration of human α-thrombin (Tmb) ranging from 10 to 100 nM. The detection limit of Tmb was determined to be 4.5 nM. Furthermore, the universality of the sensing platform was investigated by virtue of altering the Tmb aptamer sequence to the adenosine triphosphate (ATP) aptamer sequence. A linear response to the concentration of ATP ranging from 100 to 500 nM and a 60 nM detection limit were obtained.

Remote light control of drug release enhances our ability to address the complexity of biological systems because of its remarkable spatial/temporal resolution. Here, a new class of remote-controlled release system by incorporating photoacid generator (PAG) into graphene oxide-capped mesoporous silica was designed for delivering drug payloads to cancer cells via photoinduced pH-jump activation. PAG was immobilized on pore wall of the boronic acid-grafted mesoporous silica via strong physical adsorption, and then the nanoparticle was capped with graphene oxide sheet by an acid-labile boroester bond, leading to the formation of nanogated ensemble (MSP-BA-GO). Illuminating with a UV light, PAG generated a pH jump, which induced cleavage of the boroester linkers and thus resulted in the uncapping of pore gates. Moreover, folic acid-modified, doxorubicin (DOX)-loaded MSP-BA-GO (DOX@MSP-BA-GOF) showed selective cell internalization via receptor-mediated endocytosis and subsequent released DOX by the remote illumination. We envisioned that this remote-controlled drug delivery system could find potential applications for cancer therapy.

•We develop an assay for sensitive and selective genotyping of SNP.•The assay is based on L-RCA and stemless molecular beacon.•The stemless molecular beacon was formed by γ-CD and bis-pyrene labeled DNA.•The padlock DNA probe was used for recognition of a point mutation targets.A novel approach for highly sensitive and selective genotyping of single-nucleotide polymorphism (SNP) has been developed based on ligation-rolling circle amplification (L-RCA) and stemless molecular beacon. In this approach, two tailored DNA probes were involved. The stemless molecular beacon, formed through the inclusion interactions of γ-cyclodextrin (γ-CD) and bis-pyrene labeled DNA fragment, was served as signal probe. In the absence of mutant target, the two pyrene molecules were bound in the γ-CD cavity to form an excimer and showed a strong fluorescence at 475 nm. It was here named γ-CD-P-MB. The padlock DNA probe was designed as recognition probe. Upon the recognition of a point mutation DNA targets, the padlock probe was ligated to generate a circular template. An RCA amplification was then initiated using the circular template in the presence of Phi29 polymerase and dNTPs. The L-RCA products, containing repetitive sequence units, subsequently hybridized with the γ-CD-P-MB. This made pyrene molecules away from γ-CD cavity and caused a decrease of excimer fluorescence. As a proof-of-concept, SNP typing of β-thalassemia gene at position −28 was investigated using this approach. The detection limit of mutated target was determined to be 40 fM. In addition, DNA ligase offered high fidelity in distinguishing the mismatched bases at the ligation site, resulting in positive detection of mutant target even when the ratio of the wildtype to the mutant is 999:1. Given these attractive characteristics, the developed approach might provide a great genotyping platform for pathogenic diagnosis and genetic analysis.

•We develop a sensitive electrochemical assay for PKA activity and inhibition assay.•The electrochemical assay is based on AuNPs/MWNTs nanohybrids.•The assay takes advantage of intrinsic peroxidase-like activity of +AuNPs.•The MWNTs can increase the accumulation of +AuNPs and promote electron-transfer reaction.A sensitive and simple electrochemical strategy has been developed for assay of protein kinase A (PKA) activity and inhibition using gold nanoparticles/multi-walled carbon nanotubes (AuNPs/MWNTs) nanohybrids. Key features of this assay included intrinsic peroxidase-like activity of positively-charged gold nanoparticles (+AuNPs) and signal transduction and amplification of multi-walled carbon nanotubes (MWNTs). In this assay, an N-terminally cysteine-containing peptide was self-assembled onto the gold electrode via Au–S bonding and used as substrate for PKA, and adenosine-5′-(γ-thio)-triphosphate was used as co-substrate. Upon thiophosphorylation in the presence of PKA, the AuNPs/MWNTs nanohybrids would be fixed onto the peptides via Au–S bond. The conjugated AuNPs/MWNTs nanohybrids could catalyze the 3, 3′, 5, 5′-Tetramethylbenzidine (TMB) oxidation by H2O2 to form TMB oxidation product, which was reduced at the electrode surface to generate an electrochemical current. It was eT on state. The current signal intensity is proportional to the activity of PKA. Here, the presence of MWNTs not only increased the surface area for accumulation of +AuNPs but also could promote electron-transfer reaction. It was found that the electrochemical strategy can be employed to assay PKA activity with a low detection limit of 0.09 U/mL. The linear range of the assay for PKA enzymatic unit/ml was 0.1–1 U/mL. Furthermore, the interferences experiments of T4 polynucleotide kinase (T4 PNK) and Casein kinase II (CK2), and inhibition of PKA, have also been studied by using this strategy. The developed method would provide a diversified platform for kinase activity and inhibition monitoring.

A facile method for the shape-selective synthesis of silica nanostructures using a reverse-microemulsion-mediated template (RMMT) technique is reported. In this method, positive poly-l-lysine (PLL) is selected as template due to its configuration diversity. By adjusting pH and concentration, PLL demonstrates various secondary structures containing random coil, α-helix and β-sheet, which result in the formation of silica nanorods, silica nanospheres and silica nanotubes in the reverse-microemulsion system, respectively. Thus, the shape-selective synthesis of silica nanostructures might be achieved by using PLL as structural template in the reverse-microemulsion system.A facile method for the shape-selective synthesis of silica nanostructures using a reverse-microemulsion-mediated template (RMMT) technique is reported. The rod-like, spherical and tubular silica structures can be synthesized with random coil, α-helix and β-sheet structures as template, respectively.

We report here a highly sensitive and label-free electrochemical aptasensing technology for detection of interferon-gamma (IFN-γ) based on graphene controlled assembly and enzyme cleavage-assisted target recycling amplification strategy. In this work, in the absence of IFN-γ, the graphene could not be assembled onto the 16-mercaptohexadecanoic acid (MHA) modified gold electrode because the IFN-γ binding aptamer was strongly adsorbed on the graphene due to the strong π–π interaction. Thus the electronic transmission was blocked (eT OFF). However, the presence of target IFN-γ and DNase I led to desorption of aptamer from the graphene surface and further cleavage of the aptamer, thereby releasing the IFN-γ. The released IFN-γ could then re-attack other aptamers on the graphene, resulting in the successive release of the aptamers from the graphene. At the same time, the “naked” graphene could be assembled onto the MHA modified gold electrode with hydrophobic interaction and π-conjunction, mediating the electron transfer between the electrode and the electroactive indicator. Then, measurable electrochemical signals were generated (eT ON), which was related to the concentration of the IFN-γ. By taking advantages of graphene and enzyme cleavage-assisted target recycling amplification, the developed label-free electrochemical aptasensing technology showed a linear response to concentration of IFN-γ range from 0.1 to 0.7 pM. The detection limit of IFN-γ was determined to be 0.065 pM. Moreover, this aptasensor shows good selectivity toward the target in the presence of other relevant proteins. Our strategy thus opens new opportunities for label-free and amplified detection of other kinds of proteins.Highlights► We develop an electrochemical aptasensor for IFN-γ detection. ► The detection method is based on graphene and nuclease cleavage amplification. ► Signal transduction and amplification of graphene on the MHA/SAM electrode. ► It is a label-free, highly sensitive strategy for the detection of IFN-γ. ► The assay has good response in complicated cell media.

A highly sensitive and simple label-free electrochemiluminescent (ECL) sensing strategy has been developed for assay of protein kinase A (PKA) activity and inhibition by taking advantage of zirconium cation (Zr4+) mediated signal transition and signal amplification of Ru(II) encapsulated phosphorylate-terminated silica nanoparticles (R-PSiNPs). In the protocol, an N-terminally cysteine-containing peptide (S-peptide) is self-assembled onto the gold electrode via Au–S bonding and used as substrate for PKA. The R-PSiNPs are chosen as the signal indicator by virtue of the intrinsic phosphate groups on the surface of the silica nanoparticles and the high loading of Ru(II) markers for ECL signal generation and amplification. The substrate peptide on the electrode is phosphorylated by PKA in the presence of ATP. The phosphorylated peptide (P-peptide) is subsequently linked with the R-PSiNPs by Zr4+. The R-PSiNPs then can be grafted to the surface of Au electrode and generate high ECL signal. The ECL intensity is proportional to the activity of PKA. Due to the high loading of Ru(II) markers in a single phosphorylate-terminated silica nanoparticle, this strategy can be employed to assay PKA activity with a low detection limit of 0.005 U/mL. The linear range of the assay for PKA was 0.01 U/mL to 1 U/mL. Furthermore, the interferences experiments of CK2 and PKA inhibition have been also studied by using this strategy. This selective and sensitive method does not require labeling of the substrate peptide with ECL molecules, which provides a diversified platform for kinase activity and inhibition assay.Highlights► We develop an electrochemiluminescent strategy for assay PKA activity and inhibition. ► The electrochemiluminescent assay is based on Zr4+ and R-PSiNPs. ► Signal amplification of Ru(II) doped phosphorylate-terminated silica nanoparticles. ► It is a simple, sensitive, selective, and universal platform for kinases activity assay.

This paper proposed a natural gelatin capped mesoporous silica nanoparticles (MSN@Gelatin) based pH-responsive delivery system for intracellular anticancer drug controlled release. In this system, the gelatin, a proteinaceous biopolymer derived from the processing of animal collagen, was grafted onto the MSN to form a capping layer via temperature-induced gelation and subsequent glutaraldehyde mediated cross-linking, resulting in gelatin coated MSN. At neutral pH, the gelatin capping layer could effectively prohibit the release of loaded drug molecules. However, the slightly acidic environment would lead to enhanced electrostatic repulsion between the gelatin and MSN, giving rise to uncapping and the subsequent controlled release of the entrapped drug. As a proof-of-concept, doxorubicin (DOX) was selected as the model anticancer drug. The loading and pH-responsive release experiments demonstrated that the system had excellent loading efficiency (47.3 mmol g–1 SiO2), and almost no DOX was leaked at neutral. After being in the slightly acidic condition, the DOX release from the DOX-loaded MSN@Gelatin (DOX/MSN@Gelatin) occurred immediately. The cellular uptake and release studies using Hep-G2 hepatoma cells indicated that the DOX/MSN@Gelatin could be endocytosed and accumulated within lysosomes. Triggered by acidic endosomal pH, the intracellular release of the loaded DOX was obviously eventuated. Further cell viability results demonstrated that DOX/MSN@Gelatin exhibited dose-dependent toxicity and high killing efficacy (IC50 = 17.27 ± 0.63 μg mL–1), whereas the MSN@Gelatin showed negligible cytotoxicity (IC50 > 100 μg mL–1). This biocompatible and effective delivery system will provide great potential for developing delivery of cancer therapeutic agents.

Mercury (Hg2+) is a highly toxic and widespread environmental pollutant. Herein, a regenerable and highly selective core–shell structured magnetic mesoporous silica nanocomposite with functionalization of thymine (T) and T-rich DNA (denoted as Fe3O4@nSiO2@mSiO2-T-TRDNA nanocomposite) has been developed for simultaneous detection and removal of Hg2+. In this work, the thymine and T-rich DNA were immobilized onto the interior and exterior surface of outermost mesoporous silica, respectively. The detection mechanism is based on Hg2+-mediated hairpin structure formed by T-rich DNA functionalized on the exterior surface of the nanocomposites, where, upon addition of SYBR Green I dye, strong fluorescence is observed. In the absence of Hg2+, however, addition of the dye results in low fluorescence. The limit of detection for Hg2+ in a buffer is 2 nM by fluorescence spectroscopy. Simultaneously, the Fe3O4@nSiO2@mSiO2-T-TRDNA nanocomposite features a selective binding with Hg2+ between two thymines immobilized at the interior surface of the mesopores and exhibits efficient and convenient Hg2+ removal by a magnet. Kinetic study reveals that the Hg2+ removal is a rapid process with over 80% of Hg2+ removed within approximately 1 h. The applicability of the developed nanocomposites is demonstrated to detect and remove Hg2+ from samples of Xiangjiang river water spiked with Hg2+. In addition, distinguishing aspects of the Fe3O4@nSiO2@mSiO2-T-TRDNA nanocomposites for Hg2+ detection and removal also include the regeneration using a simple acid treatment and resistance to nuclease digestion. Similar process can be used to functionalize the Fe3O4@nSiO2@mSiO2 nanocomposites with other nucleic acids and small molecules for environmental and biomedical applications.

A sensitive label-free “signal-on” electrochemical approach for detection of methyltransferases (MTase) activity is developed based on the signal transduction and amplification of single wall carbon nanotubes (SWCNTs). In this method, the oligonucleotide I is first self-assembled on the electrode via Au–S bonding. After hybridization with its complement ssDNA (oligonucleotide II), duplex strand DNA (dsDNA) probes containing specific recognition sequence of Dam MTase and methylation-sensitive restriction endonuclease Dpn I is then formed on the electrode. In the presence of Dam MTase and Dpn I, the dsDNA probes are methylated and subsequently cleaved into two dsDNA fragments. After heating, the remained dsDNA fragments on the electrode melted into ssDNA fragments. Then the SWCNTs can be controllably assembled on the ssDNA fragments remained on the electrode, mediating efficient electron transfer between the electrode and electroactive species. It generates measurable current signal (eT ON), which is related to the concentration of the Dam MTase. The resulting change in electron transfer efficiency is readily measured by differential pulse voltammetry at Dam MTase concentrations as low as 0.04 U/mL. This method does not need electroactive molecules labeling on the methylation-responsive DNA probes. The linear response of the developed facile signal-on electrochemical sensing system for Dam MTase is in the range of 0.1–1.0 U/mL. In addition, such a SWCNTs based electrochemical assay also has the ability to screen inhibitors for Dam MTase.Highlights► We develop an electrochemical strategy for assay MTase activity and inhibition. ► The electrochemical assay is based on single wall carbon nanotubes. ► Signal transduction and amplification of single wall carbon nanotubes. ► It is a label-free, sensitive route for the detection of MTase activity. ► The screening of the inhibitors of MTase can be achieved based on the assay.

In this paper, a colorimetric assay for multiplexed analysis of mercury and silver ions was demonstrated by using a rationally designed unimolecular multifunctional DNA probe (UMDP) as sensing element, and unmodified gold nanoparticles (AuNPs) as color-reporting probes. The UMDP had a random coil structure that changed into two different hairpin-like structures with a T–Hg2+–T or C–Ag+–C basepairing built-in the stem upon binding Hg2+ or Ag+ ions, respectively. As a result, the conformation changes facilitated the salt-induced AuNPs aggregation, leading red-to-blue color change with a red shift of the plasmon band in the UV-visible absorption spectrum. Thus, the change in absorption intensity allowed the multiplexed detection of Hg2+ and Ag+ ions. The sensing system could detect as low as 2.5 × 10−7 M Hg2+ ions and 5 × 10−7 M Ag+ ions. Both the color and absorption changes of the system were selective for Hg2+ and Ag+ ions, which met the selective requirements for biomedical and environmental application. Moreover, the two target ions were simply distinguished by using EDTA, Hg2+ ions could not cause AuNPs aggregation while Ag+ ions still could in the presence of EDTA. Then, the colorimetric response of the two target ions in spiked lake water and tap water were tested, respectively. We expect this simple and cost-effective method to have wide-ranging applications for monitoring water quality in the developing region.

We report here a highly sensitive electrochemical sensing platform for Ag+ detection based on Ag+-induced conformational change of cytosine-rich single stranded DNA C-rich ssDNA probe and the controlled assembly of MWCNTs. In the protocol, the gold electrode was first modified with a dense 16-mercaptohexadecanoic acid self-assembled monolayer (MHA/SAM). The hydrophobic MHA/SAM isolated the electrode from the electroactive indicator in the aqueous solution, which resulted in the electronic transmission blocking. It was eT OFF state. In the presence of Ag+, C–Ag+–C coordination induced the conformational change of C-rich ssDNA probe from random-coil structure to fold into a hairpin structure, which cannot wrap on the surface of the MWCNTs. Then the “naked” MWCNTs can be assembled on the MHA/SAM gold electrode, mediating the electron transfer between the electrode and the electroactive indicator. It generated measurable electrochemical signals (eT ON). The resulting change in electron transfer efficiency was readily measured by differential pulse voltammetry at target Ag+ concentrations as low as 1.3 nM. The linear response range for Ag+ detection was from 10 to 500 nM. This method dose not need of electroactive molecules labeling on the C-rich ssDNA probe. Moreover, it has good selectivity to other environmentally relevant metal ions. Therefore, the developed electrochemical assay is an ideal method for Ag+ detection with some advantages including sensitivity, selectivity, simplicity, low-cost, and no requirement for probe label preparation. We expect that this strategy could be a generalized platform for DNA-based sensing.Highlights► An electrochemical sensing platform for Ag+ detection was developed. ► An un-labeled cytosine-rich ssDNA probe was used for Ag+ recognition. ► Controlled assembly of MWCNTs was used as signal transduction and amplification. ► The developed method is sensitive, selective, simple, and low-cost for Ag+ detection. ► This strategy could be a generalized platform for DNA-based electrochemical sensing.

In this paper, a reversible light-responsive molecule-gated system based on mesoporous silica nanoparticles (MSN) functionalized with thymine derivatives is designed and demonstrated. The closing/opening protocol and release of the entrapped guest molecules is related by a photodimerization–cleavage cycle of thymine upon different irradiation. In the system, thymine derivatives with hydrophilicity and biocompatibility were grafted on the pore outlets of MSN. The irradiation with 365 nm wavelength UV light to thymine-functionalized MSN led to the formation of cyclobutane dimer in the pore outlet, subsequently resulting in blockage of pores and strongly inhibiting the diffusion of guest molecules from pores. With 240 nm wavelength UV light irradiation, the photocleavage of cyclobutane dimer opened the pore and allowed the release of the entrapped guest molecules. As a proof-of-the-concept, Ru(bipy)32+ was selected as the guest molecule. Then the light-responsive loading and release of Ru(bipy)32+ were investigated. The results indicated that the system had an excellent loading amount (53 μmol g–1 MSN) and controlled release behavior (82% release after irradiation for 24 h), and the light-responsive loading and release procedure exhibited a good reversibility. Besides, the light-responsive system loaded with Ru(bipy)32+ molecule could also be used as a light-switchable oxygen sensor.

An aptamer is a useful molecular recognition tool for the design of various biosensors owing to their diversified structures, good biocompatibility, high affinity, and specificity for binding a wide range of non-nucleic acid targets, from small molecules to whole cells. Herein, we developed a signal on aptamer-based electrochemical sensing platform by taking advantage of a triple-helix molecular switch. In this sensing platform, two tailored DNA probes were involved for constructing a triple-helix molecular switch. One was a label-free target specific aptamer sequence (Apt) flanked by two arm segments, called as a recognition probe. The other, serving as a signal transduction probe (STP), was designed as a hairpin-shaped structure and labeled with methylene blue (MB) and a sulfhydryl group at the 3′ and 5′-end, respectively. The target specific Apt contained triple-helix DNA (Apt–THDNA) was formed by binding two arm segments of the Apt with the loop sequence of STP, and then self-assembled onto the gold electrode via Au–S bonding. Due to the “open” configuration of STP in the Apt–THDNA, the methylene blue modified on the STP was far away from the electrode. It was eT OFF state. Formation of an aptamer/target complex disassembled the Apt–THDNA and retained the STP section on the gold electrode. Subsequently, the retained STP on the gold electrode could form a hairpin-shaped configuration, mediating the methylene blue approach onto the gold electrode surface to generate redox current. It was eT on state. The developed facile signal on aptamer-based electrochemical sensing platform using a triple-helix molecular switch showed a linear response to the concentration of human α-thrombin (Tmb) ranging from 10 to 100 nM. The detection limit of Tmb was determined to be 4.5 nM. Furthermore, the universality of the sensing platform was investigated by virtue of altering the Tmb aptamer sequence to the adenosine triphosphate (ATP) aptamer sequence. A linear response to the concentration of ATP ranging from 100 to 500 nM and a 60 nM detection limit were obtained.

In this paper, a colorimetric assay for multiplexed analysis of mercury and silver ions was demonstrated by using a rationally designed unimolecular multifunctional DNA probe (UMDP) as sensing element, and unmodified gold nanoparticles (AuNPs) as color-reporting probes. The UMDP had a random coil structure that changed into two different hairpin-like structures with a T–Hg2+–T or C–Ag+–C basepairing built-in the stem upon binding Hg2+ or Ag+ ions, respectively. As a result, the conformation changes facilitated the salt-induced AuNPs aggregation, leading red-to-blue color change with a red shift of the plasmon band in the UV-visible absorption spectrum. Thus, the change in absorption intensity allowed the multiplexed detection of Hg2+ and Ag+ ions. The sensing system could detect as low as 2.5 × 10−7 M Hg2+ ions and 5 × 10−7 M Ag+ ions. Both the color and absorption changes of the system were selective for Hg2+ and Ag+ ions, which met the selective requirements for biomedical and environmental application. Moreover, the two target ions were simply distinguished by using EDTA, Hg2+ ions could not cause AuNPs aggregation while Ag+ ions still could in the presence of EDTA. Then, the colorimetric response of the two target ions in spiked lake water and tap water were tested, respectively. We expect this simple and cost-effective method to have wide-ranging applications for monitoring water quality in the developing region.

Here we present a novel large Stokes shifting NIR fluorescent nanomicelle through the encapsulation of a quantum dot/methylene blue FRET pair, which is employed as an excellent contrast reagent for NIR fluorescence bioimaging.

A sensitive turn-on fluorescent sensor based on single-layer MnO2 nanosheet-quenched fluorescent carbon quantum dots has been developed for rapid and selective sensing of glutathione in aqueous solutions, as well as in living cells.

We propose a novel template-assisted strategy to prepare nanometer-sized manganese oxide (nano-MnO2) by self-assembly of some MnO2 platelets and demonstrate its application as a new class of biosensing platform for probing DNA hybridization and aptamer–target interaction in a homogeneous solution.

Here we exploit dsDNA-specific fluorescent copper nanoparticles (CuNPs) as a “green” nano-dye for polymerization-mediated biochemical analysis. Good feasibility and universality are demonstrated through detecting three model targets (polymerase, mercury ion and nucleic acid).

Owing to the over-expressed level in pheochromocytoma cells, dopamine (DA) provides a unique opportunity to design drug delivery systems for pheochromocytoma treatment. Herein, we developed a DA responsive delivery system for the treatment of pheochromocytoma cells based on mesoporous silica nanoparticles (MSNs) capped with DNA-templated silver nanoparticles (AgNPs). In this system, cytimidine-rich DNA grafted on the MSN was employed as the template to in situ drive the synthesis of AgNPs. The as-formed AgNPs were bound to the contour of DNA and blocked the pores to form the AgNPs capped MSNs (MSN@AgNPs). In the presence of DA, the capped AgNPs would break away from the surface of MSNs due to the reactivity of DA with AgNPs through the formation of Ag–catechol bonds, giving rise to the uncapped pores. Doxorubicin (DOX), as a model drug, was used to form DOX-loaded MSN@AgNPs (DOX@MSN@AgNPs) and then to assess the drug release behaviors from the DA-responsive delivery system. The in vitro studies showed that the DOX@MSN@AgNPs have a higher cytotoxicity to rat pheochromocytoma cell lines (PC-12 cells) when compared to human cervical cancer cell lines (HeLa cells). With these excellent features, we believe that this DA-triggered drug delivery system should promote the development of therapy in pheochromocytoma.

Despite remarkable progress in the construction of functional mesoporous silica nanoparticles (MSNs) for cancer therapy, a multifunctional system with synergistic advantages over any single model remains encouraging. The objective of the present study was to develop a novel, simple and powerful nanotherapeutic system for the pH- and near-infrared (NIR)-responsive chemothermal treatment of cancer cells by co-loading coralyne and indocyanine green (ICG) into the adenine DNA (poly(A))-functionalized MSN. Coralyne, a type of planar alkaloid for cancer chemotherapy, can not only be loaded into the pores of MSN, but can also bind poly(A) and trigger the formation of non-Watson–Crick secondary structures, resulting in pore capping by the cooperative binding of poly(A) strands. Under low-pH or high-temperature conditions, non-Watson–Crick secondary structures were unstable, leading to the dehybridization of the cooperative binding structure and open-gate state. ICG, another cargo co-loaded into MSN, showed high efficiency for the conversion of NIR light into heat, which could provide the fundamental basis of hyperthermal therapy and promote pore opening upon NIR irradiation. In vitro studies using human hepatoma (HepG-2) cells demonstrated that this system could perform well in cellular acidic environment and under NIR irradiation, leading to a significant efficiency in controlled drug release and chemothermal cancer treatment. We believe that with these excellent features it should become a favorable nanoplatform for biomedical applications.

Metal–organic frameworks (MOFs) have spurred tremendous research interest in the fields of nanoscience and nanotechnology. However, exploring their biomedical applications is still a daunting challenge. In this work, we employed an acid-degradable MOF, zeolitic imidazolate framework-8 (ZIF-8), both as a self-sacrificial template to synthesize uniform size/morphology-controllable hollow mesoporous silica materials (HMSNs) and as a mesopore blocker for fabricating a pH-responsive HMSN-based drug delivery system. Starting from the ZIF-8 template, a layer of mesoporous silica is coated on ZIF-8 and subsequently the template was self-degraded under acidic conditions to obtain HMSNs. A series of monodisperse HMSNs ranging from ca. 80 nm to ca. 3000 nm with morphologies that give rare examples of cubic and dodecahedral morphologies has been prepared. It is demonstrated that the as-made HMSNs possess well-defined mesopores, huge cavities and good biocompatibility, which make them favourable for drug delivery. So, ZIF-8 was then grafted onto the HMSN to block the pore orifice for pH-responsive intracellular anticancer drug release. The results indicated that the ZIF-8-coated HMSN with encapsulated doxorubicin hydrochloride (DOX) was an efficient drug delivery vehicle in cancer therapy using pH-responsive release. This strategy sheds new light on the application of MOF materials and provides great potential for biomedical applications.

Here, we report a novel metal–organic framework-based nanocomposite with encapsulated Pd@Au nanoparticles and doxorubicin (DOX) for pH- and NIR-triggered synergistic chemo-photothermal treatment of cancer cells. In this work, Pd nanoparticles, which have uniform size and dispersibility, were first synthesized and used as a template to direct the covering of Au nanosheets. The obtained Au coated Pd (Pd@Au) nanoparticles have excellent dispersibility and photothermal conversion ability, which makes them a good photothermal nanomaterial. Subsequently, an acid-degradable metal–organic framework of ZIF-8 was employed to synchronously encapsulate Pd@Au nanoparticles and DOX to get a metal–organic framework-based nanocomposite (DOX/Pd@Au@ZIF-8). Under acid conditions (e.g. pH ∼5.0 in a lysosome), the ZIF-8 framework of the DOX/Pd@Au@ZIF-8 nanocomposite could be degraded, resulting in the release of encapsulated DOX. Moreover, the present Pd@Au nanoparticles can effectively convert NIR laser light (780 nm, 2.1 W cm−2) into heat, not only further promoting the release of DOX, but also realizing the synergistic chemo-photothermal treatment of cancer cells. The in vitro experiments showed that this nanocomposite system has an excellent synergistic treatment effect on SMMC-7721 cells, even at low concentrations (e.g. 20 μg mL−1). With the properties of synergistic chemo-photothermal treatment, we hope that such a nanocomposite system of DOX/Pd@Au@ZIF-8 could open the door to designing a significant multifunctional system for diverse applications in cancer treatment.

Resveratrol (Res) has emerged as an extremely promising natural molecule due to its vast therapeutic prospects. However, the potential of the drug is immensely hindered by several limiting factors including poor water solubility, limited chemical stability and high metabolization. Herein we report a facile synthesis of a Res-loaded folate-terminated PEG-phospholipid coated reduced graphene oxide nanoassembly (FA-PEG-Lip@rGO/Res) by simply sonicating Res and rGO in FA-PEG linked liposome (FA-PEG-liposome) suspensions. The as-obtained FA-PEG-Lip@rGO/Res exhibits a nanoscale size (148 ± 7 nm), a negative surface potential (−23.6 mV), an excellent drug loading (69.5 ± 4.3%), a high drug entrapment efficiency (86.9 ± 5.6%), good monodispersity and controlled release. Additionally, the nanoassembly can protect Res from UV-light induced instability. Owing to the folate mediated targeted delivery, the robust FA-PEG-Lip@rGO/Res can deliver loaded Res to human MCF-7 breast cancer cells with high specificity and excellent efficiency. The cell toxicity viability shows that unloaded FA-PEG-Lip@rGO has no cytotoxicity, confirming its suitability as a drug vehicle. Furthermore, a systematic in vivo study shows that, under near-infrared (NIR) laser irradiation, FA-PEG-Lip@rGO/Res exhibits highly efficient combined chemotherapy and photothermal therapy to eradicate xenografted tumor with a single dose intratumoral (i.t.) injection. Thus, a facile, stable, biocompatible, and highly-effective Res delivery system has been developed, which may greatly advance the application of Res in biomedical research.

Despite the remarkable progress in the construction of nanostructures for drug delivery in cancer therapy, multifunctional nanoplatforms with synergistic advantages over any single-model nanostructures are still encouraging. Herein, a dual pH- and near-infrared (NIR)-responsive nanotherapeutic system for the chemothermal treatment of cancer cells was achieved by using adenine DNA coated gold nanorod vehicles (poly(A)/AuNR). The poly(A)/AuNRs were prepared by self-assembling thiolated poly(A) on the surface of the AuNRs via Au–S bonding. In this system, the poly(A) provided the ability to load coralyne, a model chemotherapeutic drug, through adenine–coralyne–adenine specific binding. Under low-pH or high-temperature conditions, adenine–coralyne–adenine would be unstable, leading to the stimuli-responsive release of coralyne for cancer chemotherapy. The AuNRs showed a high efficiency for the conversion of NIR light into heat, providing the fundamental basis of hyperthermal cancer therapy, and also promoting the triggered release of coralyne from poly(A) upon NIR irradiation. The characteristics of the poly(A)/AuNRs have been investigated by using TEM and UV-vis spectroscopy. It was shown that about 160 copies of poly(A) could be assembled on one AuNR prepared with the dimensions of about 30 nm in length and 10 nm in width, and each poly(A)/AuNR could load about 2500 coralyne molecules. The in vitro studies using human hepatoma SMMC-7721 cells demonstrated that the coralyne loaded poly(A)/AuNRs could be endocytosed and demonstrated an efficient operation in a cellular acidic environment and NIR irradiation, leading to significant cytotoxicity through the excellent chemothermal synergistic effects. We believe that this developed multimode nanostructure will provide potential applications for cancer therapy.

In this paper, we report the assembly of reduced graphene oxide (RGO) and mesoporous silica grafted with alkyl chains (MSN-C18) to develop a new class of drug carriers which are able to deliver the loaded drug molecules into living cells upon exposure to near-infrared (NIR) light. This novel drug carrier consists of a structure formed by the noncovalent interaction of RGO caps and alkyl chains on the surface of MSN-C18. The capping of RGO sheets on mesoporous silica effectively blocks the pore mouths in the absence of NIR light. Conversely, and very importantly, the photothermal heating effect of RGO leads to a rapid increase in the local temperature upon exposure to NIR light, resulting in the weakening of the RGO sheet/alkyl chain noncovalent interaction. The RGO sheets will then be removed from the MSN surface, and the pores are uncapped. This uncapping mechanism makes it possible to release the loaded drug molecules upon irradiation with NIR light. In the present study, such a noncovalent assembly was examined by the use of doxorubicin as a model drug for NIR light-responsive intracellular controlled release studies. We believe that this noncovalent assembly will prove to be a promising drug delivery system for cancer therapy in the near future.

Redox-responsive degradable honeycomb manganese oxide (hMnO2) nanostructures consisting of some lamellar MnO2 platelets were established as a new class of drug carriers for intracellular glutathione-triggered drug release.