Nanoscaled Porphyrinic Metal–Organic Frameworks for Electrochemical Detection of Telomerase Activity via Telomerase Triggered Conformation Switch

In this work, we designed a nanoscaled porphyrinic metal–organic framework (PorMOF) with iron porphyrin as linker and zirconium ion as node for electrochemical detection of telomerase activity. The as-prepared PorMOF was characterized with scanning electron microscopy, powder X-ray diffraction, and spectroscopic techniques and demonstrated excellent electrocatalytic activity toward O₂ reduction. Sequentially, the functionalization of PorMOF with streptavidin results in a water-stable electrochemical tracer for detection of telomerase. Upon the telomerase-triggered extension, the assistant DNA 1 (aDNA1)–assistant DNA 2 (aDNA2) duplex could switch into a hairpin structure, and thus, the aDNA2 was released and then hybridized with the capture DNA. Therefore, the PorMOF@SA tracer could be introduced on the electrode surface via biotin–streptavidin recognition, leading to the strong electrochemical signal for readout. The developed approach displayed desirable dynamic range and limitation of detection down to 30 HeLa cells mL^–1. The telomerase activity was 2.2 × 10^–11 IU in a single HeLa cell with good reproducibility and stability. The nanoscaled porphyrinic MOF provided a powerful platform for electrochemical signal transduction and had a promising application in the determination of various biomolecules

MicroRNA-Responsive Cancer Cell Imaging and Therapy with Functionalized Gold Nanoprobe

Integration of cancer cell imaging and therapy is critical to enhance the theranostic efficacy and prevent under- or overtreatment. Here, a multifunctional gold nanoprobe is designed for simultaneous miRNA-responsive fluorescence imaging and therapeutic monitoring of cancer. By assembling with folic acid as the targeted moiety and a dye-labeled molecular beacon (MB) as the recognition element and signal switch, the gold nanoprobe is folate receptor-targeted delivered into the cancer cells, and the fluorescence is lighted with the unfolding of MB by intracellular microRNA (miRNA), resulting in an efficient method for imaging and detecting nucleic acid. The average quantity of miRNA-21 is measured to be 1.68 pg in a single HeLa cell. Upon the near-infrared irradiation at 808 nm, the real-time monitoring and assessing of photothermal therapeutic efficacy is achieved from the further enhanced fluorescence of the dye-labeled MB, caused by the high photothermal transformation efficiency of the gold nanocarrier to unwind the remaining folded MB and depart the dye from the nanocarrier. The fluorescence monitoring is also feasible for applications in vivo. This work provides a simple but powerful protocol with great potential in cancer imaging, therapy, and therapeutic monitoring

Anodic Electrochemiluminescence of CdTe Quantum Dots and Its Energy Transfer for Detection of Catechol Derivatives

This work reported for the first time the anodic electrochemiluminescence (ECL) of CdTe quantum dots (QDs) in aqueous system and its analytical application based on the ECL energy transfer to analytes. The CdTe QDs were modified with mercaptopropionic acid to obtain water-soluble QDs and stable and intensive anodic ECL emission with a peak value at +1.17 V (vs Ag/AgCl) in pH 9.3 PBS at an indium tin oxide (ITO) electrode. The ECL emission was demonstrated to involve the participation of superoxide ion produced at the ITO surface, which could inject an electron into the 1Se quantum-confined orbital of CdTe to form QDs anions. The collision between these anions and the oxidation products of QDs led to the formation of the excited state of QDs and ECL emission. The ECL energy transfer from the excited CdTe QDs to quencher produced a novel methodology for detection of catechol derivatives. Using dopamine and l-adrenalin as model analytes, this ECL method showed wide linear ranges from 50 nM to 5 μM and 80 nM to 30 μM for these species. Both ascorbic acid and uric acid, which are common interferences, did not interfere with the detection of catechol derivatives in practical biological samples

Host–Guest Interaction of Adamantine with a β‑Cyclodextrin-Functionalized AuPd Bimetallic Nanoprobe for Ultrasensitive Electrochemical Immunoassay of Small Molecules

A modular labeling strategy was presented for electrochemical immunoassay via supramolecular host–guest interaction between β-cyclodextrin (β-CD) and adamantine (ADA). An ADA-labeled antibody (ADA–Ab) was synthesized via amidation, and the number of ADA moieties loaded on a single antibody was calculated to be ∼7. The β-CD-functionalized gold–palladium bimetallic nanoparticles (AuPd–CD) were synthesized in aqueous solution via metal-S chemistry and characterized with transmission electron microscopy and X-ray photoelectron spectra. After the ADA–Ab was bound to the antigen-modified electrode surface with a competitive immunoreaction, AuPd–CD as a signal tag was immobilized onto the immunosensor by a host–guest interaction, leading to a large loading of AuPd nanoparticles. The highly efficient electrocatalysis by AuPd nanoparticles for NaBH₄ oxidation produced an ultrasensitive response to chloramphenicol as a model of a small molecule antigen. The immunoassay method showed a wide linear range from 50 pg/mL to 50 μg/mL and a detection limit of 4.6 pg/mL. The specific recognition of antigen by antibody resulted in good selectivity for the proposed method. The host–guest interaction strategy provided a universal labeling approach for the ultrasensitive detection of small molecule targets

Multifunctional Metal–Organic Framework Nanoprobe for Cathepsin B‑Activated Cancer Cell Imaging and Chemo-Photodynamic Therapy

Integration of a photodynamic therapy platform with a drug-delivery system in a porous structure is an urgent challenge for enhanced anticancer therapy. Here, an amino-functionalized metal–organic framework (MOF), which is useful as efficient delivery vehicle for drugs and provides the −NH2 group for postsynthetic modification, is chosen and well-designed for cell imaging and chemo-photodynamic therapy. The multifunctional MOF nanoprobe was first assembled with camptothecine drug via noncovalent encapsulation and then bound with folic acid as the targeted element and chlorine e6 (Ce6)-labeled CaB substrate peptide as the recognition moiety and signal switch. The designed MOF probe can realize cathepsin B-activated cancer cell imaging and chemo-photodynamic dual-therapy combining Ce6 as the photosensitizer and the camptothecine drug. Compared with the individual treatment, the dual-functional nanoprobe presents an enhanced treatment efficiency in terms of the time of chemotherapy, laser power, and irradiation time of the photodynamic therapy, which has been confirmed in cancer cells and in vivo assays. This work presents a significant example of the MOF nanoprobe as an intracellular switch and shows great potential in cancer cell targeted imaging and multiple therapies

Self-Assembled DNA Hydrogel as Switchable Material for Aptamer-Based Fluorescent Detection of Protein

The methodology based on target-responsive structural switching is powerful in bioanalysis with the controllability and sensitivity. In this paper, an aptamer-functionalized DNA hydrogel was designed as a specifically target-responsive switchable material for protein detection. This pure DNA hydrogel was constructed by using a Y-shaped DNA and an aptamer linker through a DNA self-assembly without synthetic polymer backbone. With use of thrombin as the model analyte, the DNA hydrogel was first applied to visual detection with the entrapped Au nanoparticles (AuNPs) as indicating agent. Furthermore, the positively charged quantum dots (QDs) as the fluorophore were synthesized by using polyethyleneimine (PEI) as wrapper and characterized with spectroscopy, transmission electron micrograph, ζ potential, and dynamic laser scattering techniques. Along with a gel-to-sol transition in the presence of the target, the released negatively charged AuNPs from the hydrogel could approach the positively charged QDs. Due to the electrostatic interaction, fluorescence resonance energy transfer between PEI-QDs and AuNPs therefore occurred and quenched the fluorescence signal for the sensitive detection of thrombin. This assay for the detection of thrombin showed a good linear relationship in a range of 0.075 to 12.5 μM with a detection limit of 67 nM at 3σ, and demonstrated excellent feasibility in complex serum matrixes. The biocompatible DNA hydrogel provides a universal switchable material for signal transduction and significantly demonstrates proof-of-concept for the detection of proteins

Portable Photoelectrochemical Device Integrated with Self-Powered Electrochromic Tablet for Visual Analysis

A portable photoelectrochemical (PEC) device is developed by intergating a self-powered electrochromic tablet for visual analysis. The tablet consists of an electron-injector (EI) part for photo-to-electric conversion and an electrochromic (EC) part for visualized readout, which are coated with dye-sensitized titanium dioxide film and Ni-doped tungsten trioxide (WO₃) film, respectively. Under the illumination of a white LED light, the photoexcited electrons generated from EI part convey to EC part through the conductive inner side of indium tin oxide slide and would cause color change of the Ni-doped WO₃ film in the presence of protons. Furthermore, the Ni-doped WO₃ film exhibits excellent transmittance modulation of more than 80%, providing an enhanced signal for visual analysis. Using pyrophosphate ion (PPi) as a model analyte, we have successfully constructed a visualized PEC sensing platform based on the formation of blue-colored hydrogen tungsten bronzes via the hydrolysis reaction of PPi. Being equipped with a small light source and a dark box, the PEC tablet as a portable device can perform colorimetric measurement with good reversibility and stability. This smart PEC device provides important reference for future studies on the visual application in practice

Photocurrent Polarity Reversal Induced by Electron-Donor Release for the Highly Sensitive Photoelectrochemical Detection of Vascular Endothelial Growth Factor 165

Photocurrent polarity reversal is a switching process between the anodic and cathodic pathways and is critical for eliminating false positivity and improving detection sensitivity in photoelectrochemical (PEC) sensing. In this study, we construct a PEC sensor with excellent photocurrent polarity reversal induced by ascorbic acid (AA) as an electron donor with the energy level matching the photoactive material zirconium metal–organic framework (ZrMOF). The ZrMOF-modified electrode demonstrates cathodic photocurrent in the presence of O2 as an electron acceptor, while the anodic photocurrent is generated in the presence of AA, achieving photocurrent polarity reversal. By the in situ release of AA from AA-encapsulated apoferritin modified with DNA 2 (AA@APO-S2) as a detection tag in the presence of trypsin after the recognition of hairpin DNA-modified indium tin oxide to the reaction product of aptamer/DNA 1 with the target protein and the following rolling cycle amplification for introducing the detection tag to the sensing interface, the reversed photocurrent shows an enhanced photocurrent response to the target protein, leading to a highly sensitive PEC sensing strategy. This strategy realizes the detection of vascular endothelial growth factor 165 with good specificity, a wide linear range, and a low detection limit down to 5.3 fM. The actual sample analysis offers the detection results of the proposed PEC sensor comparable to those of commercial enzyme-linked immunosorbent assay tests, indicating the promising application of the photocurrent polarity reversal-based PEC sensing strategy in biomolecule detection and clinical diagnosis