Schottky Junction Nanozyme Based on Mn-Bridged Co-Phthalocyanines and Ti3C2Tx Nanosheets Boosts Integrative Type I and II Photosensitization for Multimodal Cancer Therapy.

Cancer phototheranostics have the potential for significantly improving the therapeutic effectiveness, as it can accurately diagnose and treat cancer. However, the current phototheranostic platforms leave much to be desired and are often limited by tumor hypoxia. Herein, a Schottky junction nanozyme has been established between a manganese-bridged cobalt-phthalocyanines complex and Ti3C2Tx MXene nanosheets (CoPc-Mn/Ti3C2Tx), which can serve as an integrative type I and II photosensitizer for enhancing cancer therapeutic efficacy via a photoacoustic imaging-guided multimodal chemodynamic/photothermal/photodynamic therapy strategy under near-infrared (808 nm) light irradiation. The Schottky junction not only possessed a narrow-bandgap, enhanced electron-hole separation ability and exhibited a potent redox potential but also enabled improved H2O2 and O2 supplying performances in vitro. Accordingly, the AS1411 aptamer-immobilized CoPc-Mn/Ti3C2Tx nanozyme illustrated high accuracy and excellent anticancer efficiency through a multimodal therapy strategy in in vitro and in vivo experiments. This work presents a valuable method for designing and constructing a multifunctional nanocatalytic medicine platform for synergistic cancer therapy of solid tumors.

Electrochemical aptasensing strategy based on a multivariate polymertitanium-metal-organic framework for zearalenone analysis.

An electrochemical aptasensing strategy was developed with a novel bioplatform based on a multivariate titanium metal-organic framework, i.e. MTV polyMOF(Ti), to detect zearalenone (ZEN). MTV polyMOF(Ti) was prepared by using mixed linkers of polyether polymer (pbdc-xa or L8, pbdc = poly(1,4-benzenedicarboxylate) and 1,4-benzenedicarboxylic acid (H2bdc or L0) as well as tetrabutyl titanate as nodes (MTV polyMOF(Ti)-L8,0). Compared with Ti-MOFs synthesized by using the single ligand of L8 or L0, MTV polyMOF(Ti)-L8,0 shows more porous structure assembled with multilayered nanosheets. In light of the improved electrochemical activity and strong bioaffinity to the aptamer, the aptasensor based on MTV polyMOF(Ti)-L8,0 shows excellent performance for detecting ZEN with the ultralow detection limit at fg mL-1 level in the linear range of 10 fg mL-1 to 10 ng mL-1, along with good selectivity, reproducibility, stability, regenerability, and applicability.

Surface plasmon resonance aptasensor based on niobium carbide MXene quantum dots for nucleocapsid of SARS-CoV-2 detection.

A novel label-free surface plasmon resonance (SPR) aptasensor has been constructed for the detection of N-gene of SARS-CoV-2 by using thiol-modified niobium carbide MXene quantum dots (Nb2C-SH QDs) as the bioplatform for anchoring N-gene-targeted aptamer. In the presence of SARS-CoV-2 N-gene, the immobilized aptamer strands changed their conformation to specifically bind with N-gene. It thus increased the contact area or enlarged the distance between aptamer and the SPR chip, resulting in a change of the SPR signal irradiated by the laser (He-Ne) with the wavelength (λ) of 633 nm. Nb2C QDs were derived from Nb2C MXene nanosheets via a solvothermal method, followed by functionalization with octadecanethiol through a self-assembling method. Subsequently, the gold chip for SPR measurements was modified with Nb2C-SH QDs via covalent binding of the Au-S bond also by self-assembling interaction. Nb2C-SH QDs not only resulted in high bioaffinity toward aptamer but also enhanced the SPR response. Thus, the Nb2C-SH QD-based SPR aptasensor had low limit of detection (LOD) of 4.9 pg mL-1 toward N-gene within the concentration range 0.05 to 100 ng mL-1. The sensor also showed excellent selectivity in the presence of various respiratory viruses and proteins in human serum and high stability. Moreover, the Nb2C-SH QD-based SPR aptasensor displayed a vast practical application for the qualitative analysis of N-gene from different samples, including seawater, seafood, and human serum. Thus, this work can provide a deep insight into the construction of the aptasensor for detecting SARS-CoV-2 in complex environments. A novel label-free surface plasmon resonance aptasensor has been constructed to detect sensitively and selectively the N-gene of SARS-CoV-2 by using thiol-modified niobium carbide MXene quantum dots as the scaffold to anchor the N-gene-targeted aptamer.

Ruthenium(II) 1,4,7-trithiacyclononane complexes of curcumin and bisdemethoxycurcumin: Synthesis, characterization, and biological activity.

Two cationic ruthenium(II) 1,4,7-trithiacyclononane ([9]aneS3) complexes of curcumin (curcH) and bisdemethoxycurcumin (bdcurcH), namely [Ru(curc)(dmso-S)([9]aneS3)]Cl (1) and [Ru(bdcurc)(dmso-S)([9]aneS3)]Cl (2) were prepared from the [RuCl2(dmso-S)([9]-aneS3)] precursor and structurally characterized, both in solution and in the solid state by X-ray crystallography. The corresponding PTA complexes [Ru(curc)(PTA)([9]aneS3)]Cl (3) and [Ru(bdcurc)(PTA)([9]aneS3)]Cl (4) have been also synthesized and characterized (PTA = 1,3,5-triaza-7-phosphaadamantane). Bioinorganic studies relying on mass spectrometry were performed on complexes 1-4 to assess their interactions with the model protein lysozyme. Overall, a rather limited reactivity with lysozyme was highlighted accompanied by a modest cytotoxic potency against three representative cancer cell lines. The moderate pharmacological activity is likely connected to the relatively high stability of these complexes.

Semiconducting CuxNi3-x(hexahydroxytriphenylene)2 framework for electrochemical aptasensing of C6 glioma cells and epidermal growth factor receptor.

A 2D CuNi metal-organic framework (MOF) named CuxNi3-x(HHTP)2 was synthesized with 2,3,6,7,10,11-hexahydroxytriphenylene (HHTP) as the linker and was used as a sensitive scaffold to adsorb aptamer strands for the electrochemical detection of living C6 glioma cells and one of their biomarkers, epidermal growth factor receptor (EGFR). Different from conventional MOFs, the CuxNi3-x(HHTP)2 MOF comprises long-range delocalized electrons, a graphene-analog nanostructure, multiple metal states (Cu0/Cu+/Cu2+ and Ni2+/Ni3+), and abundant oxygen vacancies. With these features, the CuxNi3-x(HHTP)2 MOF anchored a large amount of C6 cell-targeted aptamer strands via coordination among metal centers, oligonucleotides, π-π stacking, and van der Waals force. The CuxNi3-x(HHTP)2-based cytosensor showed a low limit of detection (LOD) of 21 cells mL-1 toward C6 glioma cells within a wide range from 50 cells mL-1 to 1 × 105 cells mL-1. Moreover, the proposed aptasensor displayed high selectivity, good stability, acceptable reproducibility, and a low LOD of 0.72 fg mL-1 for detecting EGFR with the concentration ranging from 1 fg mL-1 to 1 ng mL-1. The aptasensor based on the CuxNi3-x(HHTP)2 MOF exhibited superior sensing performance over those based on its monometallic analogues such as Cu3(HHTP)2 MOF and Ni3(HHTP)2 MOF. Hence, this sensing strategy based on a bimetallic semiconducting MOF shows great potential for cancer diagnosis.

A multiple aptasensor for ultrasensitive detection of miRNAs by using covalent-organic framework nanowire as platform and shell-encoded gold nanoparticles as signal labels.

We report herein a novel multiple electrochemical aptasensor based on covalent-organic framework (COF) for sensitive and simultaneous detection of miRNA 155 and miRNA 122, by using shell-encoded gold nanoparticles (Au NPs) as signal labels (AgNCs@AuNPs and Cu2O@AuNPs, respectively, NCs = nanoclusters). A new COF nanowire was synthesized via condensation polymerization of 1,3,6,8-tetra(4-carboxylphenyl)pyrene and melamine (represented by TBAPy-MA-COF-COOH) for multiple aptasensor fabrication. The nanowire was then used as a platform for anchoring single-strand DNA (ssDNA), which was hybridized with the complementary aptamer (cApt) probes of miRNA 155 and miRNA 122. AgNCs@AuNPs and Cu2O@AuNPs modified with cApts show separated differential pulse voltammetry (DPV) peaks at 0.08 and -0.1 V, respectively. The signal labels immobilized with cApts were released from the hybridized DNA complex and bound to their corresponding targets when contacting miRNAs. This phenomenon results in the substantial decline of the DPV peak current density of the signal labels. The developed TBAPy-MA-COF-COOH-based aptasensor has superior performance for sensing miRNA 155 and miRNA 122 simultaneously, with ultrasensitive low detection limits of 6.7 and 1.5 fM (S/N = 3), respectively, a wide linear range of 0.01-1000 pM, and high selectivity and applicability for serum samples. The proposed TBAPy-MA-based aptasensor demonstrates potential for simultaneous detection of multiple cancer biomarkers by replacing other ssDNA and aptamer strands.

Bimetallic cerium/copper organic framework-derived cerium and copper oxides embedded by mesoporous carbon: Label-free aptasensor for ultrasensitive tobramycin detection.

We reported a novel bimetallic cerium/copper-based metal organic framework (Ce/Cu-MOF) and its derivatives pyrolyzed at different temperatures, followed by exploiting them as the scaffold of electrochemical aptamer sensors for extremely sensitive detection of trace tobramycin (TOB) in human serum and milk. After the calcination at high temperature, the meal coordination centers (Ce and Cu) were transferred to metal oxides containing various chemical valences, such as Ce(III), Ce(IV), Cu(II) and Cu(0), which were embedded within the mesoporous carbon network originated from the organic ligands (represented by CeO2/CuOx@mC). Owning to the strong synergistic effect among the metal oxides, mesoporous carbon, and small cavities and open channels of MOF, the as-prepared CeO2/CuOx@mC nanocomposites not only possess good electrochemical activity but also exhibit strong bioaffinity toward the aptamer strands. By comparing the electrochemical biosensing peroformances using on the Ce/Cu-MOF- and the series of CeO2/CuOx@mC-based aptasensors, the constructed CeO2/CuOx@mC900-based (calcinated at 900 °C) aptasensor exhibits an extremely low detection limit of 2.0 fg mL-1 within a broad linear TOB concentration range from 0.01 pg mL-1 to 10 ng mg L-1. It demonstrates that the proposed aptasensor is substantially superior to those previously reported in the literature, along with high selectivity, good stability and reproducibility, and acceptable applicability in human serum and milk. Thereby, the newly fabricated aptasensing approach based on bimetallic CeO2/CuOx@mC has a considerable potential for the quantitative detection of antibiotics in the food safety and biomedical field.

Bifunctional aptasensor based on novel two-dimensional nanocomposite of MoS2 quantum dots and g-C3N4 nanosheets decorated with chitosan-stabilized Au nanoparticles for selectively detecting prostate specific antigen.

A novel nanostructured biosensing platform was designed based on two-dimensional (2D) nanocomposite of graphitic carbon nitride (g-C3N4) nanosheets and MoS2 quantum dots (MoS2 QDs), followed by decoration with chitosan-stabilized Au nanoparticles (CS-AuNPs) (denoted as MoS2QDs@g-C3N4@CS-AuNPs), of which CS-AuNPs were prepared by plasma enhanced-chemical vapor deposition. Owning to the good surface plasmon performance of the CS-AuNPs and excellent electrochemical activity of MoS2QDs@g-C3N4 nanosheets, the as-obtained 2D MoS2QDs@g-C3N4@CS-AuNPs nanocomposite was simultaneously explored to construct both surface plasmon resonance spectroscopy (SPR) sensor and electrochemical aptasensor. The MoS2QDs@g-C3N4@CS-AuNPs-based aptasensor shows strong bio-binding affinity toward the prostate specific antigen (PSA) targeted aptamer strands as compared to the individual component, including MoS2 QDs, g-C3N4, and CS-AuNPs. When detecting PSA, the low limit of detection (LOD) of 0.71 pg mL-1 deduced by electrochemical aptasensor is three orders of magnitude lower than that deduced by SPR sensor (0.77 ng mL-1). As expected, both SPR sensor and electrochemical aptasensor demonstrate good selectivity, highly stability, acceptable reproducibility, and well consistent applicability in human serum. The satisfactory results suggest potential application of the MoS2QDs@g-C3N4@CS-AuNPs in bifunctional biosensing fields and clinical monitoring of cancer markers.

Aptamer-Embedded Zirconium-Based Metal-Organic Framework Composites Prepared by De Novo Bio-Inspired Approach with Enhanced Biosensing for Detecting Trace Analytes.

A series of Zr-based metal-organic framework (MOF) composites embedded with three kinds of aptamer strands (509-MOF@Apt) were achieved by a one-step de novo synthetic approach. A platform for ultrasensitive detection of analytes, namely, thrombin, kanamycin, and carcinoembryonic antigen (CEA), was also established. Considering the conformational changes caused by the binding interactions between aptamer strands and targeted molecules, the label-free electrochemical aptasensors based on 509-MOF@Apt composites could be developed to detect various target molecules. By comparing the common fabrication approaches of aptasensors, a distinct determination mechanism was presented through analysis of the electrochemical measurements on different interaction behaviors between probe aptamer strands and 509-MOF materials. The optimized aptasensors based on 509-MOFs@Apt demonstrated excellent sensitivity (with the detection limit of 0.40, 0.37, and 0.21 pg mL-1 for CEA, thrombin, and kanamycin, respectively), stability, repeatability, and applicability. This work will provide a new platform for direct and feasible detection in biosensing related to clinical diagnostics and therapeutics, and further, extend the scope of potential applications for MOF materials.

Pore modulation of zirconium-organic frameworks for high-efficiency detection of trace proteins.

Tunable electrochemical biosensors based on analogous Zr-MOFs were developed for protein detection, the performances of which rely on the pore sizes and surroundings of the MOFs that show diverse binding behaviors to aptamers and then the targeted proteins. The optimized Zr-MOF-based sensor has high selectivity to lysozyme in a wide concentration range and a low detection limit of 3.6 pg mL-1, with good repeatability, stability, and applicability in real samples. This work will establish a new platform for biosensing and extend the application scope of MOF materials.