Nanoscale Metal-Organic Frameworks as a Photoluminescent Platform for Bioimaging and Biosensing Applications.

The tracking of nanomedicines in their concentration and location inside living systems has a pivotal effect on the understanding of the biological processes, early-stage diagnosis, and therapeutic monitoring of diseases. Nanoscale metal-organic frameworks (nano MOFs) possess high surface areas, definite structure, regulated optical properties, rich functionalized sites, and good biocompatibility that allow them to excel in a wide range of biomedical applications. Controllable syntheses and functionalization endow nano MOFs with better properties as imaging agents and sensing units for the diagnosis and treatment of diseases. This minireview summarizes the tunable synthesis strategies of nano MOFs with controllable size, shape, and regulated luminescent performance, and pinpoints their recent advanced applications as optical elements in bioimaging and biosensing. The current limitations and future development directions of nano MOF-contained materials in bioimaging and biosensing applications are also discussed, aiming to expand the biological applications of nano MOF-based nanomedicine and facilitate their production or clinical translation.

Metal-Organic Framework as a New Type of Magnetothermally-Triggered On-Demand Release Carrier.

The development of external stimuli-controlled payload systems has been sought after with increasing interest toward magnetothermally-triggered drug release (MTDR) carriers due to their non-invasive features. However, current MTDR carriers present several limitations, such as poor heating efficiency caused by the aggregation of iron oxide nanoparticles (IONPs) or the presence of antiferromagnetic phases which affect their efficiency. Herein, a novel MTDR carrier is developed using a controlled encapsulation method that fully fixes and confines IONPs of various sizes within the metal-organic frameworks (MOFs). This novel carrier preserves the MOF's morphology, porosity, and IONP segregation, while enhances heating efficiency through the oxidation of antiferromagnetic phases in IONPs during encapsulation. It also features a magnetothermally-responsive nanobrush that is stimulated by an alternating magnetic field to enable on-demand drug release. The novel carrier shows improved heating, which has potential applications as contrast agents and for combined chemo and magnetic hyperthermia therapy. It holds a great promise for magneto-thermally modulated drug dosing at tumor sites, making it an exciting avenue for cancer treatment.

A Microporous Metal-Organic Framework with Unique Aromatic Pore Surfaces for High Performance C2 H6 /C2 H4 Separation.

Developing adsorptive separation processes based on C2 H6 -selective sorbents to replace energy-intensive cryogenic distillation is a promising alternative for C2 H4 purification from C2 H4 /C2 H6 mixtures, which however remains challenging. During our studies on two isostructural metal-organic frameworks (Ni-MOF 1 and Ni-MOF 2), we found that Ni-MOF 2 exhibited significantly higher performance for C2 H6 /C2 H4 separation than Ni-MOF-1, as clearly established by gas sorption isotherms and breakthrough experiments. Density-Functional Theory (DFT) studies showed that the unblocked unique aromatic pore surfaces within Ni-MOF 2 induce more and stronger C-H⋅⋅⋅π with C2 H6 over C2 H4 while the suitable pore spaces enforce its high C2 H6 uptake capacity, featuring Ni-MOF 2 as one of the best porous materials for this very important gas separation. It generates 12 L kg-1 of polymer-grade C2 H4 product from equimolar C2 H6 /C2 H4 mixtures at ambient conditions.

A Microporous Hydrogen-Bonded Organic Framework for Efficient Xe/Kr Separation.

Separation of xenon/krypton gas mixtures is one of the valuable but challenging processes in the gas industries due to their close molecular size and similar physical properties. Here, we report a novel ultramicroporous hydrogen-bonded organic framework (termed as HOF-40) constructed from a cyano-based organic building unit of 1,2,4,5-tetrakis(4-cyanophenyl)benzene (TCPB), exhibiting superior separation performance for Xe/Kr mixtures, as clearly demonstrated by dynamic breakthrough curves. GCMC simulation results indicate that the pore confinement effect and abundant accessible binding sites play a synergistic role in this challenging gas separation. Furthermore, this cyano-based HOF displays excellent chemical stability from 12 M HCl to 20 M NaOH aqueous solutions.

Metal-Organic Framework Based Hydrogen-Bonding Nanotrap for Efficient Acetylene Storage and Separation.

The removal of carbon dioxide (CO2) from acetylene (C2H2) is a critical industrial process for manufacturing high-purity C2H2. However, it remains challenging to address the tradeoff between adsorption capacity and selectivity, on account of their similar physical properties and molecular sizes. To overcome this difficulty, here we report a novel strategy involving the regulation of a hydrogen-bonding nanotrap on the pore surface to promote the separation of C2H2/CO2 mixtures in three isostructural metal-organic frameworks (MOFs, named MIL-160, CAU-10H, and CAU-23, respectively). Among them, MIL-160, which has abundant hydrogen-bonding acceptors as nanotraps, can selectively capture acetylene molecules and demonstrates an ultrahigh C2H2 storage capacity (191 cm3 g-1, or 213 cm3 cm-3) but much less CO2 uptake (90 cm3 g-1) under ambient conditions. The C2H2 adsorption amount of MIL-160 is remarkably higher than those for the other two isostructural MOFs (86 and 119 cm3 g-1 for CAU-10H and CAU-23, respectively) under the same conditions. More importantly, both simulation and experimental breakthrough results show that MIL-160 sets a new benchmark for equimolar C2H2/CO2 separation in terms of the separation potential (Δqbreak = 5.02 mol/kg) and C2H2 productivity (6.8 mol/kg). In addition, in situ FT-IR experiments and computational modeling further reveal that the unique host-guest multiple hydrogen-bonding interaction between the nanotrap and C2H2 is the key factor for achieving the extraordinary acetylene storage capacity and superior C2H2/CO2 selectivity. This work provides a novel and powerful approach to address the tradeoff of this extremely challenging gas separation.

Concentration-Dependent Subcellular Distribution of Ultrasmall Near-Infrared-Emitting Gold Nanoparticles.

The ability to accurately control the subcellular distribution of nanomedicines provides unique advantages on understanding of cellular biology and disease theranostics. The nanomedicine concentration is a key factor to affect the theranostic efficiency and systematic toxicity. Herein, we unravel a concentration-dependent subcellular distribution of near-infrared-emitting gold nanoparticles (AuNPs) co-coated with glutathione and a cell-penetrating peptide CR8 (CR-AuNPs), which shows a strong membrane-binding at high concentration but more endocytosis for mitochondria targeting at the low concentration region. Attributing to high content of AuI and microsecond luminescent lifetimes, these AuNPs can catalyze dissolved oxygen to generate singlet oxygen (1 O2 ) efficiently. Combining with the concentration-dependent subcellular distribution, the luminescent AuNPs show photocytotoxicity in the relative low concentration region. These findings facilitate the fundamental understanding of the biological behaviors and potential cytotoxicity of ultrasmall luminescent AuNPs toward future theranostics.

Metal-Organic Frameworks as a Versatile Platform for Proton Conductors.

Metal-organic frameworks (MOFs) are an intriguing type of crystalline porous materials that can be readily built from metal ions or clusters and organic linkers. Recently, MOF materials, featuring high surface areas, rich structural tunability, and functional pore surfaces, which can accommodate a variety of guest molecules as proton carriers and to systemically regulate the proton concentration and mobility within the available space, have attracted tremendous attention for their roles as solid electrolytes in fuel cells. Recent advances in MOFs as a versatile platform for proton conduction in the field of humidity condition proton-conduction, anhydrous atmosphere proton-conduction, single-crystal proton-conduction, and including MOF-based membranes for fuel cells, are summarized and highlighted. Furthermore, the challenges, future trends, and prospects of MOF materials for solid electrolytes are also discussed.

Self-Assembly of Luminescent Gold Nanoparticles with Sensitive pH-Stimulated Structure Transformation and Emission Response toward Lysosome Escape and Intracellular Imaging.

Ultrasmall luminescent gold nanoparticles (AuNPs, d < 3.0 nm) with distinct optical properties and good biocompatibilities hold enormous promise for advanced disease theranostics. However, ultrasmall AuNPs generally show low cellular interaction and are hardly ever transported into the specific subcellular compartments, hampering their further biomedical use in cellular delivery and intracellular tracking. Using a conventional cationic polymer chitosan (CS) with the isoelectric point of 6.5 as a template, ultrasmall luminescent AuNPs can be easily formed into self-assembled nanostructures (AuNPs@CS) with significantly enhanced cellular interaction capability and sensitive emission response toward subcellular location. The self-assembled AuNPs@CS become compacted nanostructures (∼23.5 nm) with high luminescence at low pH values (e.g., pH < 6.5) but reversibly transform to swelled structures with weak luminescence at high pH values (e.g., pH 7.4). The self-assembly of AuNPs not only improves the emission properties but also alters the surface charge and assembly size, resulting in both enhanced cellular internalization and effective endosomal escape capability. More importantly, the sensitive luminescence response of the AuNPs@CS from the acidic organelle lysosome to the neutral cytoplasm demonstrates the great potential in optical intracellular tracking.

Surface Coverage-Regulated Cellular Interaction of Ultrasmall Luminescent Gold Nanoparticles.

Investigations for accurately controlling the interaction between functional nanoparticles (NPs) and living cells set a long-thought benefit in nanomedicine and disease diagnostics. Here, we reveal a surface coverage-dependent cellular interaction by comparing the membrane binding and uptake of three ultrasmall luminescent gold NPs (AuNPs) with different surface coverages. Lower surface coverage leads to fast cellular interaction and strong membrane binding but low cellular uptake, whereas high surface coverage induces slow cellular interaction and low membrane binding but major cellular uptake. The slight number increase of cell-penetrating peptide on the surface of AuNPs shows improved cellular interaction dynamics and internalization through direct cellular membrane penetration. Furthermore, the different intrinsic emissions resulted from the surface coverage variation, especially the pH-responsive dual emissions, make the AuNPs powerful optical probes for subcellular imaging and tracking. The findings advance the fundamental understanding of the cellular interaction mechanisms of ultrasmall AuNPs and provide a feasible strategy for the design of functional NPs with tunable cellular interaction by surface regulation.

Amphiphilic Block Copolymer-Guided in Situ Fabrication of Stable and Highly Controlled Luminescent Copper Nanoassemblies.

Assembling instable ultrasmall nanoparticles (NPs) into uniform nanoarchitectures with excellent stability and controllability in aqueous solution is still challenging. Herein, taking the advantage of controllable size and shape of amphiphilic triblock copolymer template, we report a facile and robust strategy for in situ fabrication of highly luminescent Cu nanoassemblies with uniform morphology and remarkable stability. The dominant number of encapsulated CuNPs in an assembly can be controlled through regulating hydrophobic core size by varying block segments of the template. The cross-linking by a multidentate thiol ligand largely enhances the emission and stability of the Cu nanoassemblies in physiological environment. By virtue of their intriguing features, the Cu nanoassemblies can be applied to possible biomedical applications. These findings establish our approach as a facile and feasible method for preparing stable and well-controlled ultrasmall metal NP-based assemblies.

Reactivity Toward Ag+: A General Strategy to Generate a New Emissive Center from NIR-Emitting Gold Nanoparticles.

We report a facile strategy for the transformation of single NIR-emitting AuNPs to dual-NIR-emitting bimetallic Ag@AuNPs based on the robust reactivity toward Ag(I) ions under mild conditions. The reactivities toward Ag(I) ions were found to be significantly different between visible- and NIR-emitting glutathione (GSH)-coated AuNPs: the high GSH surface coverage on the 610 nm-emitting AuNPs resulted in a reversible interaction due to enough surface steric hindrance to resist Ag(I) ions from interaction with the Au(0) core, whereas the low GSH surface coverage on the 810 nm-emitting AuNPs led to both antigalvanic reaction and Ag(I)-carboxylate shell formation on the surface of the AuNPs, which were responsible for the formation of a new emissive center at 705 nm. This strategy was also demonstrated to exhibit excellent generalization toward various NIR-emitting AuNPs with surface chemistries containing carboxyl groups, opening a new pathway of tailoring the optical properties of metallic NPs through surface reactivity.

Transformation from gold nanoclusters to plasmonic nanoparticles: A general strategy towards selective detection of organophosphorothioate pesticides.

Luminescent gold nanoclusters (AuNCs) synthesized using non-thiolate DNA ligands were reported to show both optical and structure responses toward diethyposphorthioate (DEP) derived from the hydrolysis of chlorpyrifos (CP). After incubation of AuNCs with DEP, the non-thiolate DNA ligands were immediately replaced and the tiny AuNCs with ultrasmall size transformed gradually to plasmonic nanoparticles, which resulted in significant luminescence quenching of the AuNCs, offering a new possibility to selectively detect organophosphorothioate pesticides that could be easily hydrolyzed to form the special structures such as DEP containing two binding sites (e.g. S and O atoms). Therefore, selecting CP as a model analyte, we here developed a general strategy for the construction of a novel chemosensor for the determination of CP using the non-thiolate DNA coated AuNCs as an optical probe. Based on aggregation-induced luminescence quenching, this strategy exhibited highly sensitive and selective responses towards CP with a limit of detection (LOD) of 0.50µM, and was applied successfully to the analysis of CP in real sample. More interestingly, this facile strategy could easily distinguish CP from other thiol reagents through solution color change in spite of the existence of the coordination between Au and S atom for both of them, and the response mechanisms for them were studied in detail. In additional, it could be extended to detect the other organophosphorothioate pesticides with the similar structure as CP, which exploits a new platform for the construction of chemosensor and application.

Bioapplications of renal-clearable luminescent metal nanoparticles.

Renal-clearable inorganic nanoparticles (NPs) that hold great potential in the future clinic translations are considered as the next generation of nanomedicine. In the past decade, enormous efforts have been dedicated to the development of renal-clearable NPs with fascinating optical properties, selective disease-targeting capabilities and low nanotoxicities. A further understanding of the design of renal-clearable luminescent metal NPs and their metabolic behavior in the body is important to achieve their clinical transition and extend their bioapplications in disease theranostics. In this review, we discuss the recent synthetic strategies of renal-clearable metal NPs in terms of the considerations of size and composition, surface chemistry and emission wavelength. We also summarize the current disease-related applications of these renal-clearable luminescent metal NPs in tumor targeting, kidney disease and antimicrobial investigations after a discussion of their biological behavior including the pharmacokinetics and biodistribution. Finally, we provide perspectives on the current challenges and upcoming chances for renal-clearable luminescent metal NPs.

Silver Iodide-Chitosan Nanotag Induced Biocatalytic Precipitation for Self-Enhanced Ultrasensitive Photocathodic Immunosensor.

In this work, we first exposed that the application of p-type semiconductor, silver iodide-chitosan nanoparticle (SICNP), acted as peroxidase mimetic to catalyze the bioprecipitation reaction for signal-amplification photocathodic immunosensing of human interleukin-6 (IL-6). After immobilization of captured antibody onto a polyethylenimine-functionalized carbon nitride (CN) matrix, SICNPs as photoactive tags and peroxidase mimetics were labeled on secondary antibodies, which were subsequently introduced onto the sensing interface to construct sandwich immunoassay platform through antigen-antibody specific recognition. Due to the matched energy levels between CN and AgI, the photocurrent intensity and photostability of SICNP were dramatically improved with rapid separation and transportation of photogenerated carriers. Moreover, the insoluble product in effective biocatalytic precipitation reaction served as electron acceptor to scavenge the photoexcited electron, leading to great amplification of the photocurrent signal of SICNP again. With the help of multiamplification processes, this photocathodic immunosensor presented a turn-on photoelectrochemical performance for IL-6, which showed wide linear dynamic range from 10(-6) to 10 pg/mL with the ultralow detection limit of 0.737 ag/mL. This work also performed the promising application of SICNP in developing an ultrasensitive, cost-effective, and enzyme-free photocathodic immunosensor for biomarkers.

All-in-one bioprobe devised with hierarchical-ordered magnetic NiCo2O4 superstructure for ultrasensitive dual-readout immunosensor for logic diagnosis of tumor marker.

A new enzyme-free all-in-one bioprobe, consisted of hematin decorated magnetic NiCo2O4 superstructure (ATS-MNS-Hb), was designed for ultrasensitive photoelectrochemical and electrochemical dual-readout immunosensing of carcinoembryonic antigen (CEA) on carbon nanohorns (CNH) support. Herein, the MNS, possessed hierarchical-ordered structure, good porosity and magnetism, acted as nanocarrier to absorb abundant Hb molecular after functionalization, providing a convenient collection means by magnetic control as well as enhanced dual-readout sensing performances. CNH superstructures were employed as support to immobilize abounding captured antibodies, and then as-designed dual mode bioprobe, covalent binding with secondary antibody of CEA, was introduced for ultrasensitive detection of CEA by sandwich immunosensing. Photoelectrochemical response originated from plentiful hematin molecular, a excellent photosensitizer with good visible light harvesting efficiency, absorbed by functionalized porous MNS. The resultant concentration dependant linear calibration range was from 10 fg/mL to 1 ng/mL with ultralow detection limit of 10 fg/mL. For electrochemical process, catalase-like property of MNS was validated, moreover, MNS-Hb hybrid exhibited much higher mimic enzyme catalytic activity and evidently amplified electrocatalytic signal, performing a wide dynamic linear range from 1 ng/mL to 40 ng/mL with low detection limit of 1 ng/mL. Additionally, due to the improved accuracy of dual signals detection, the exact diagnoses of serum samples were gotten by operating resulting dual signals with AND logic system. This work demonstrated the promising application of MNS in developing ultrasensitive, cost-effective and environment friendly dual-readout immunosensor and accurate diagnoses strategy for tumor markers.

The photoelectrochemical exploration of multifunctional TiO2 mesocrystals and its enzyme-assisted biosensing application.

Mesocrystals, as the assemblies of crystallographically oriented nanocrystals, have single-crystal-like atom structures and scattering features but with much higher porosity than single-crystalline materials, making them promising substitutes for conventional single crystals in photoelectrochemical application. As a proof-of-concept, a series of photoelectrochemical tests were investigated to understand the influence of the differences between them on photoelectrochemical activity. Expectedly, comparing with TiO2 single crystals, TiO2 mesocrystals demonstrated higher photoelectrochemical capability, which provides unique new opportunities for materials design in the fields of solar-energy conversion and catalysis. Therefore, an elegant photoelectrochemical biosensing platform was firstly developed by virtue of carbon nanohorns with outstanding electrical conductivity support multifunctional TiO2 mesocrystals to accelerate the transfer of photogenerated electrons, and then horseradish peroxidase was introduced through the immune recognition reaction for enzyme-assisted in situ generating CdS QDs. The multiplex amplification strategy successfully achieved the ultrasensitive detection of α-fetoprotein antigen. Promisingly, the successful application of multiplex amplification strategy affords a rational and practical consideration for the fabrication of new and high-performance photoelectrochemical sensing devices.

TiO2-B nanorod based competitive-like non-enzymatic photoelectrochemical sensing platform for noninvasive glucose detection.

TiO2-B nanorods, with excellent properties including large specific surface area, open structures with significant voids, and continuous channels, were explored for the first time in the photoelectrochemical biosensing field. To reduce the destructive effect of UV light on biomolecules, dopamine was introduced onto the TiO2-B nanorod surface through the coordination of dopamine to the undercoordinated titanium atoms of the TiO2-B nanorods, which makes the complex a promising matrix for subsequent biosensing. Furthermore, concanavalin A as a recognition element was attached onto the TiO2-B nanorod/dopamine modified electrode surface by virtue of covalent interaction between concanavalin A and dopamine. Accordingly, a new competitive-like non-enzymatic photoelectrochemical biosensor was established by using glucose labeled SiO2 nanospheres of fixed concentration as photoelectrochemical signal inhibitors competing with target glucose of various concentrations for reaction with concanavalin A. Moreover, this ultrasensitive biosensor with excellent analytical performance was successful applied to noninvasive glucose determination in human saliva. Promisingly, the successful application of TiO2-B nanorods in this research provides a new consideration in the selection of excellent photoactive materials for photoelectrochemical sensing.

An electrochemical impedimetric sensor based on biomimetic electrospun nanofibers for formaldehyde.

Herein, simple molecular recognition sites for formaldehyde were designed on electrospun polymer nanofibers. In order to improve the conductivity of the electrospun polymer nanofibers, carbon nanotubes were introduced into the resulting nanofibers. By employing these functionalized nanocomposite fibers to fabricate a biomimetic sensor platform, an obvious change caused by recognition between recognition sites and formaldehyde molecules was monitored through electrochemical impedance spectroscopy (EIS). The experimental conditions were optimized and then a quantitative method for formaldehyde sensing in low concentration was established. The relative results demonstrated that the sensor based on biomimetic recognition nanofibers displays an excellent recognition capacity toward formaldehyde. The linear response range of the sensor was between 1 × 10(-6) mol L(-1) and 1 × 10(-2) mol L(-1), with the detection limit of 8 × 10(-7) mol L(-1). The presented research provided a fast, feasible and sensitive method for formaldehyde with good anti-interference capabilities and good stability, which could meet the practical requirement for formaldehyde assay.

Carbon nanotubes functionalized electrospun nanofibers formed 3D electrode enables highly strong ECL of peroxydisulfate and its application in immunoassay.

A new biosensing platform based on electrospun carbon nanotubes nanofibers (CNTs@PNFs) composite, which enabled strong electrochemiluminescent emission of peroxydisulfate, was firstly developed for immunoassay with favorable analytical performances, and then was utilized to evaluate the interaction between antibody and antigen in vitro. Moreover, the obvious ECL image of peroxydisulfate on the prepared sensing platform was firstly recorded in this report. In order to expand the application of peroxydisulfate ECL, the specific recognization biomolecules, α-fetoprotein (AFP) antibody was bound to the functionalized film via electrostatic interaction for fabricating label-free ECL immunosensor to detect α-AFP. Based on the ECL change resulting from the specific immunoreaction between antigen and antibody, the quantitative analysis for AFP with wide dynamic response in the range from 0.1 pg mL(-1) to 160 ng mL(-1) was realized. And the limit of detection was estimated to be 0.09 pg mL(-1). Therefore, the flexible sensing platform not only acted as the sensitized sensing element, but also offered a suitable carrier for immobilization of biological recognition elements with low-toxicity and eco-friendliness, which opened a promising approach to developing further electrospun nanofiber based amplified ECL biosensor with favorable analytical performances.

Electrochemiluminescence of luminol at the titanate nanotubes modified glassy carbon electrode.

A new strategy for the construction of a sensitive and stable electrochemiluminescent platform based on titanate nanotubes (TNTs) and Nafion composite modified electrode for luminol is described, TNTs contained composite modified electrodes that showed some photocatalytic activity toward luminol electrochemiluminescence emission, and thus could dramatically enhance luminol light emission. This extremely sensitive and stable platform allowed a decrease of the experiment electrochemiluminescence luminol reagent. In addition, in luminol solution at low concentrations, we compared the capabilities of a bare glassy carbon electrode with the TNT composite modified electrode for hydrogen peroxide detection. The results indicated that compared with glassy carbon electrode this platform was extraordinarily sensitive to hydrogen peroxide. Therefore, by combining with an appropriate enzymatic reaction, this platform would be a sensitive matrix for many biomolecules.