Microneedles-Based Theranostic Platform: From the Past to the Future.

Fully integrated theranostic devices are highly esteemed in clinical applications, offering immense potential in real-time disease monitoring and personalized care. Microneedles (MNs), as innovative and wearable devices, boast important advantages in biosensing and therapy, thus holding significant promise in the advancement of diagnostic and therapeutic platforms. Encouragingly, advancements in electrochemical sensing technology, micronano fabrication, and biocompatible materials are propelling momentum for MNs-based closed-loop systems, enhancing detection capabilities, biocompatibility, and cost-effectiveness. Moreover, the notable progress in integrating MN chips with other biochips signifies a frontier for growth. Successful clinical trials in target molecule monitoring and drug delivery domains herald excellent clinical translational prospects for the aforementioned theranostic platform. Finally, we delineate both challenges and opportunities in the development of integrated diagnostic and therapeutic MN systems, including continuous monitoring, intelligent control algorithms, safety, and regulatory considerations.

Engineered E. coli for Long-Term Oral Enzyme Delivery.

Intestinal flora shows excellent affinity in the gut, and the adhesive property is borrowed for oral drug delivery. A facile strategy for bacteria engineering has been successfully developed by introducing metal-organic framework (MOF) mineralization. The MOF exoskeleton serves as an extendable platform for accommodating various cargoes with good Escherichia coli morphology maintained. The artificial exoskeleton surrounding E. coli is employed for encapsulating macromolecules as a therapeutic cargo, maintaining good bioactivity with high immobilization efficiency (60%) after systematic optimization of the MOF precursor. Leveraging the natural affinity of E. coli in the gut, the in-vivo tracking of MOF-engineered E. coli in the gastrointestinal tract confirmed excellent adhesion to the GI mucosa and a 17.9-fold increase in the gut retention half-time, demonstrating significant advantages in retention capability. In comparison, the control group without E. coli equipment resulted in quick gut passage. Furthermore, the artificially engineered E. coli serves as an effective carrier for macromolecules without notable oral toxicity, as evidenced by biocompatibility evaluations in cells and animals. Overall, the MOF-engineered E. coli provides an extendable platform for loading on-demand cargoes in versatile therapeutic functions with promising clinical transnationality for long-term applications.

Lab on the Microneedles: A Wearable Metal-organic Frameworks-Based Sensor for Visual Monitoring of Stress Hormone.

Abnormal secretion and dysrhythmias of cortisol (CORT) are associated with various diseases such as sleep disorders, depression, and chronic fatigue. Wearable devices are a cutting-edge technology for point-of-care detection and dynamic monitoring of CORT with inspiring convenience. Herein, we developed a minimally invasive skin-worn device with the advanced integration of both interstitial fluid (ISF) sampling and target molecule sensing for simultaneous detection of CORT via a microneedle-based sensor with high sensitivity, excellent efficiency, and outstanding reproducibility. In the microneedle patch, swellable hydrogel was employed as the adsorption matrix for ISF extraction. Meanwhile, europium metal-organic frameworks (Eu-MOF) wrapped in the matrix played a vital role in CORT recognition and quantitative analysis. The wearable and label-free Eu-MOF-loaded microneedle patch exhibited high sensitivity in CORT detection with the detection limit reaching 10-9 M and excellent selectivity. Molecular dynamics simulation-driven mechanism exploration revealed that the strong interface interaction promoted fluorescence quenching of Eu-MOF. Moreover, in vitro and in vivo investigation confirmed the feasibility and reliability of the sensing method, and excellent biocompatibility was validated. Overall, a sensitive approach based on the wearable Eu-MOF microneedle (MN) patch was established for the simultaneous detection of CORT via visible fluorescence quenching with exciting clinical-translational ability.

Metal-organic frameworks-based microtrapper for real-time monitoring of targeted analyte and mechanism study.

Interstitial fluid (ISF) provides important information of clinical value and physiological significance beyond blood tests for obtaining more precise health information and disease theranostics. Generally, current strategies are limited to simple extraction with time-consuming follow-up procedures. Facing challenges in efficient and real-time monitoring of target analytes in transdermal ISF, we develop metal-organic framework (MOF)-functionalized microneedle (MN) patches to achieve efficient antibiotics sampling, coupling direct analysis in real time mass spectrometry (DART-MS). The MOF MN microtrapper is constructed in a double-layered structure with a hard core and a better tissue penetration was accomplished. The MOF-based microtrapper manifests good in-vitro and in-vivo antibiotics tracking capability with a semi-quantitative method established. Moreover, the hydrogen-bond driven interaction is clarified by using molecular dynamics simulations (MDS) and related computational analysis. Good penetration safety is confirmed by histological analysis with promising clinical transnationality. We anticipate MOF MN-based microdevices provide a versatile minimally invasive strategy for transdermal ISF extraction and an extendable platform for a range of target molecules monitoring, including drugs, metabolites, biomarkers, et c, with promising clinical transnationality.

Dynamic omnidirectional adhesive microneedle system for oral macromolecular drug delivery.

Oral drug administration remains the preferred route for patients and health care providers. Delivery of macromolecules through this route remains challenging because of limitations imposed by the transport across the gastrointestinal epithelium and the dynamic and degradative environment. Here, we present the development of a delivery system that combines physical (microneedle) and nonphysical (enhancer) modes of drug delivery enhancement for a macromolecule in a large animal model. Inspired by the thorny-headed intestinal worm, we report a dynamic omnidirectional mucoadhesive microneedle system capable of prolonged gastric mucosa fixation. Moreover, we incorporate sodium N-[8-(2-hydroxybenzoyl) amino] caprylate along with semaglutide and demonstrate enhanced absorption in swine resistant to physical displacement in the gastric cavity. Meanwhile, we developed a targeted capsule system capable of deploying intact microneedle-containing systems. These systems stand to enable the delivery of a range of drugs through the generation and maintenance of a privileged region in the gastrointestinal tract.

Molecular cytogenetic characterization and fusarium head blight resistance of five wheat-Thinopyrum intermedium partial amphiploids.

BACKGROUND: Partial amphiploids created by crossing octoploid tritelytrigia(2n = 8× = 56, AABBDDEE) and Thinopyrum intermedium (2n = 6× = 42, StStJJJSJS) are important intermediates in wheat breeding because of their resistance to major wheat diseases. We examined the chromosome compositions of five wheat-Th. intermedium partial amphiploids using GISH and multicolor-FISH. RESULTS: The result revealed that five lines had 10-14 J-genome chromosomes from Th. intermedium and 42 common wheat chromosomes, using the J-genomic DNA from Th. bessarabicum as GISH probe and the oligo probes pAs1-1, pAs1-3, AFA-4, (GAA) 10, and pSc119.2-1 as FISH probe. Five lines resembled their parent octoploid tritelytrigia (2n = 8× = 56, AABBDDEE) but had higher protein contents. Protein contents of two lines HS2-2 and HS2-5 were up to more than 20%. Evaluation of Fusarium head blight (FHB) resistance revealed that the percent of symptomatic spikelets (PSS) of these lines were below 30%. Lines HS2-2, HS2-4, HS2-5, and HS2-16 were less than 20% of PPS. Line HS2-5 with 14 J-genome chromosomes from Th. intermedium showed the best disease resistance, with PSS values of 10.8% and 16.6% in 2016 and 2017, respectively. CONCLUSIONS: New wheat-Th. intermedium amphiploids with the J-genome chromosomes were identified and can be considered as a valuable source of FHB resistance in wheat breeding.

Modification of metal-organic framework composites as trackable carriers with fluorescent and magnetic properties.

A fluorescent metal-organic framework (EuMOF) based on Eu3+ nodes coordinated by 1,1':2',1″-terphenyl-4,4',4″,5'-tetracarboxylate (H4ttca) linkers has been developed as a trackable carrier with inherent fluorescence. Since Fe3O4 nanoparticles (NPs) have great value in versatile applications in vivo/vitro including imaging, cell isolation and magnetic responsivity, Fe3O4 NPs were introduced in the EuMOF composites to enhance the multifunctionalities. It has been demonstrated that the Fe3O4 NPs functionalized EuMOF composites have capability for tumor cell retrieval from matrix followed by anti-cancer drug release, which is promising to be developed as an integrated drug screening platform. Cytotoxicity was evaluated and the EuMOF-based nanocomposite exhibits significantly greater (up to 4x) biocompatibility tested on MCF-7 cells than the Zn-based MOF (the same ligand). Moreover, the EuMOF nanocarrier is capable of loading and releasing anti-cancer drugs in a controllable manner, where Doxorubicin (Dox) functionalized as a payload. Controllable release was successfully achieved after incubation with tumor cells and endocytosis analysis was obtained through the fluorescent imaging which offers monitoring of apoptosis after cargo release. Overall, fluorescent/magnetic properties of EuMOF has been investigated systematically, making it easy to be tracked in potential in vivo/vitro applications. As a drug carrier, it is biocompatible and shows highly efficient drug loading within 5 min, holding great promise in potential therapeutic delivery and other clinical applications.

Development and Molecular Cytogenetic Characterization of Cold-Hardy Perennial Wheatgrass Adapted to Northeastern China.

Cold-hardy perennial wheatgrass plays an important role in the use of barren land for farming, soil and water conservation, variety improvement, and also for increasing grass yield. By crossing octoploid tritelytrigia (2n = 8x = 56, AABBDDEE) with Thinopyrum intermedium (2n = 6x = 42, StStJJJ S J S ), we developed 34 lines of perennial wheatgrass from F1 to F6 generations, which had vigorous regrowth and cold hardiness. The cold-hardy, perennial wheatgrass lines were well-adapted to the cold environment and developed root and rhizomes, with a longevity between 5 and 11 years and a better seed set. Some of them maintained wheat chromosomes beneficial for breeding perennial wheat. Molecular cytogenetic analysis demonstrated that the Th. intermedium chromosomes contributed the most to the synthetic genome of the wheatgrass hybrids and were associated with the perennial growth habit and winter hardiness. They were also preferentially maintained and transmitted to the progenies. Some wheat chromosomes were also transmitted from the F1 to F6 generations, although they were eliminated in each life cycle of the wheatgrass hybrids. The numbers of wheat and Th. intermedium chromosomes affected seed set and perennial growth habit. Seed set increased with the establishment of a more balanced genomic constitution in later generations. The cold-hardy and perennial wheatgrass lines were produced, which can be the starting point of domestication effort aimed at producing well-adapted ground cover plants under extreme environments.

Selective and efficient adsorption of Au (III) in aqueous solution by Zr-based metal-organic frameworks (MOFs): An unconventional way for gold recycling.

Recycling precious metals from secondary resources is of great environmental and economic significance. In this study, the Zr-based MOFs UiO-66-NH2 was synthesized and used to adsorb Au (III) in aqueous solution. The ultrafine particle size (∼50 nm), excellent crystallinity and huge specific surface area (1039.2 m2 ·g-1) were verified by transmission electron microscope (TEM), powder X-ray diffraction (PXRD) and surface area analysis. About 50 % Au (III) was adsorbed within 6 min and the maximum adsorption capacity at 298 K reached up to 650 mg·g-1, showing superiority to traditional adsorbents. The general order kinetics model and Liu equation were suitable to describe the adsorption process, which was spontaneous, endothermic and driven by the increasing system entropy. Electrostatic attraction between -NH3+ and Au (III) anions and inner complexation to Zr-OH played a vital role in adsorption. Au (Ⅲ) was reduced to Au° by amino groups via redox reaction certified by X-ray photoelectron spectroscopy (XPS), PXRD and high-resolution transmission electron microscopy (HRTEM) analysis. Moreover, UiO-66-NH2 displayed high selectivity, robust stability and excellent reusability, making it an ideal candidate for gold recycling in industrial practice.

Magnetization of 3-dimentional homochiral metal-organic frameworks for efficient and highly selective capture of phosphopeptides.

Enrichment of phosphopeptides based on various affinity probes prior to mass spectrometry detection is usually required due to the low abundance and low ionization efficiency of phosphopeptides. In this work, a 3-dimentional homochiral metal-organic frameworks (MOFs) was modified with magnetic nanoparticles using a facile method and then utilized for phosphopeptides capture with high efficiency and specificity. Based on magnetic solid phase extraction, a rapid and efficient method was developed and the whole enrichment procedure could be easily finished within 10min. Efficient and highly selective capture of phosphopeptides from tryptic digests and human serum was achieved. This affinity probe showed satisfactory reproducibility of the particle synthesis and could be recycled for at least seven times. With all the advantages mentioned above, this strategy is of great potential for routine application in phosphoproteomes.

NiCoMnO4: A Bifunctional Affinity Probe for His-Tagged Protein Purification and Phosphorylation Sites Recognition.

A bifunctional affinity probe NiCoMnO4 was designed and prepared with controllable morphology and size using facile methods. It was observed that the probe could be applied in His-tagged proteins purification and phosphopeptides enrichment simply through the buffer modulation. NiCoMnO4 particles showed satisfactory cycling performance for His-tagged proteins purification and broad pH-tolerance of loading buffer for phosphopeptides affinity. Therefore, a high-throughput, cost-effective, and efficient protein/peptide purification method was developed within 10 min based on the novel bifunctional affinity probe.

[Synthesis and applications of chiral metal-organic framework in the selective separation of enantiomers].

Chirality is a universal phenomenon in nature. Chiral separation is vitally important in drug development, agricultural chemistry, pharmacology, environmental science, biology and many other fields. Chiral metal-organic frameworks (MOFs) are a new group of porous materials with special topology and designable pore structures, as well as their high specific surface area, porosity, excellent thermal stability, solvent resistance, etc. Thus, chiral MOFs are promising with various applications in the field of analytical chemistry. This review summarizes the synthesis strategies of chiral MOFs and their applications in the selective separation of enantiomers, as well as related mechanism.

Recent advances in applications of nanomaterials for sample preparation.

Sample preparation is a key step for qualitative and quantitative analysis of trace analytes in complicated matrix. Along with the rapid development of nanotechnology in material science, numerous nanomaterials have been developed with particularly useful applications in analytical chemistry. Benefitting from their high specific areas, increased surface activities, and unprecedented physical/chemical properties, the potentials of nanomaterials for rapid and efficient sample preparation have been exploited extensively. In this review, recent progress of novel nanomaterials applied in sample preparation has been summarized and discussed. Both nanoparticles and nanoporous materials are evaluated for their unusual performance in sample preparation. Various compositions and functionalizations extended the applications of nanomaterials in sample preparations, and distinct size and shape selectivity was generated from the diversified pore structures of nanoporous materials. Such great variety make nanomaterials a kind of versatile tools in sample preparation for almost all categories of analytes.

Facile synthesis of magnetic homochiral metal-organic frameworks for "enantioselective fishing".

Magnetic functionalized homochiral metal-organic frameworks (MOFs) were prepared and applied to efficient enantioselective fishing of chiral drug intermediates. Under optimized conditions, the enantiomeric excess (ee) value as high as 85.2% was achieved for methyl phenyl sulfoxide (MPS) within 3 min.