Mesoporous MOFs with ROS scavenging capacity for the alleviation of inflammation through inhibiting stimulator of interferon genes to promote diabetic wound healing.

Excessive production of reactive oxygen species (ROS) and inflammation are the key problems that impede diabetic wound healing. In particular, dressings with ROS scavenging capacity play a crucial role in the process of chronic wound healing. Herein, Zr-based large-pore mesoporous metal-organic frameworks (mesoMOFs) were successfully developed for the construction of spatially organized cascade bioreactors. Natural superoxide dismutase (SOD) and an artificial enzyme were spatially organized in these hierarchical mesoMOFs, forming a cascade antioxidant defense system, and presenting efficient intracellular and extracellular ROS scavenging performance. In vivo experiments demonstrated that the SOD@HMUiO-MnTCPP nanoparticles (S@M@H NPs) significantly accelerated diabetic wound healing. Transcriptomic and western blot results further indicated that the nanocomposite could inhibit fibroblast senescence and ferroptosis as well as the stimulator of interferon genes (STING) signaling pathway activation in macrophages mediated by mitochondrial oxidative stress through ROS elimination. Thus, the biomimetic multi-enzyme cascade catalytic system with spatial ordering demonstrated a high potential for diabetic wound healing, where senescence, ferroptosis, and STING signaling pathways may be potential targets.

Hierarchically Porous MOFs Synthesized by Soft-Template Strategies.

The past few decades have been witnessing the rapid research boom of metal-organic frameworks (MOFs), which are assembled from metal nodes and multitopic organic linkers. In virtue of their modular assembly mode, they can be tailored according to desired functions to satisfy numerous potential applications. However, most initially reported MOFs were restricted to the microporous regime, limiting their practical applications with bulk molecules involved. Therefore, the research attention was immediately directed toward enlarging the intrinsic pore size of frameworks by extending the secondary building units or organic ligands. Unfortunately, the synthesis of more extended ligands is frequently tedious, and the most resultant MOFs are not sufficiently stable, restricting their popularization. The soft-template strategy is recognized as a promising avenue to produce hierarchically porous MOFs (HPMOFs), although early attempts generally failed due to the incompatibility between the surfactant self-assembly and guided crystallization process of MOF precursors in the organic phase. Therefore, developing a rational soft-template strategy to achieve the precise control of morphology and porosity of HPMOFs is of great significance.In this Account, we present our recent progress on the development and applications of HPMOFs prepared by soft-template strategies. We highlight the key issues upon using the soft-template strategy to synthesize HPMOFs. To enhance the interaction between the template and MOF precursor, a long-chain monocarboxylic acid strategy is introduced to synthesize HPMOFs with irregular mesopores in the organic phase. Then, to improve the order of mesopores, an aqueous-phase synthesis method using amphoteric surfactants as templates is developed to prepare ordered HPMOFs. To further enlarge the pore size and make the synthesis conditions of MOFs compatible with the self-assembly of surfactants, a salting-in species-induced self-assembly strategy is proposed and coupled with the structure-directing properties of copolymer templates to synthesize a series of HPMOFs with large mesopores and even macropores. This salting-in ion-mediated self-assembly (SIMS) strategy paves the way to modify the pore size, pore structure, morphology, and chemical composition of HPMOFs. The separated but intimately interconnected hierarchical pores in the resultant HPMOFs can not only realize rapid mass transport but also isolate different-size guest molecules so that they are competent for a broad range of applications including protein digestion, cascade catalysis, enzyme-assisted substrate sensing, and DNA cleavage. Finally, the limitations, challenges, and future developments of this rapidly evolving field are described. This Account with a highlight to the soft-template strategies not only provides interesting insights to understand the assembly process between templates and MOFs but also inspires an optimization of the properties of HPMOFs from diverse aspects for desired applications.

Photodynamic and Its Concomitant Ion-Interference Synergistic Therapies Based on Functional Hierarchically Mesoporous MOFs.

Although ion-interference therapy (IIT) has become an intriguing option for cancer treatment, the generation of interference ions on-demand remains a challenge. Herein, a nanoplatform based on hierarchically mesoporous metal-organic frameworks (HMMOFs) is adopted to integrate black phosphorus quantum dots (BPQDs) and meso-tetra(4-carboxyphenyl) porphine (TCPP) to realize controllable phosphate anions (PAs) production in a specific cancerous region for IIT. The uniform large mesopores of HMMOFs could guarantee the selective screening and immobilization of ultra-small and monodispersed BPQDs. The TCPP in microporous domains of HMMOFs could effectively produce 1 O2 , which not only serves as photosensitizer for photodynamic therapy (PDT), but also switches on the release of PAs from BPQDs in the adjacent mesoporous domains to trigger the concomitant synergetic IIT. The elaborated nanoplatform (BP@HMUiO-66-TCPP) presents good biocompatibility, biodegradability as well as enhanced synergetic therapeutic effects. In murine models treated with BP@HMUiO-66-TCPP, the tumor inhibition rate is as high as ≈98.24% as compared to that of the control group after 14 days treatment. Moreover, the tumor volumes in the synergetic group are only 19.6% of those in the PDT alone treated group. Such a concept of exogenous photo-controlled synergistic therapeutics might be extended to a broad range of IIT for an improved antitumor efficacy.

Specific Screening of Prostate Cancer Individuals Using an Enzyme-Assisted Substrate Sensing Platform Based on Hierarchical MOFs with Tunable Mesopore Size.

Rapid and specific identification of tumor metabolic markers is of great significance. Herein, a convenient, reliable and specific strategy was proposed to screen prostate cancer (PCa) individuals through indirectly quantifying sarcosine, an early indicator of PCa, in the clinical urine samples. The success roots in the rational design of a cascade response model, which takes integrated sarcosine oxidase (SOX) as a specific recognition unit and oxygen-sensitive molecule as a signal reporter. The newly developed hierarchical mesoporous Zr-based metal-organic frameworks with continuously tunable mesopore size ensure the synergetic work of the SOX and response unit spatially separated in their neighboring mesoporous and microporous domains, respectively. The large mesopore up to 12.1 nm not only greatly enhances the loading capacity of SOX but also spares enough space for the free diffusion of sarcosine. On this basis, the probe is competent to specifically check out the tiny concentration change of sarcosine in the urine sample between PCa patients and healthy humans. Such a concept of enzyme-assisted substrate sensing could be simply extended by altering the type of immobilized enzymes, hopefully setting a guideline for the rational design of multiple probes to quantify specific biomarkers in complex biological samples.

In Situ Coupling of Catalytic Centers into Artificial Substrate Mesochannels as Super-Active Metalloenzyme Mimics.

Highly evolved substrate channels in natural enzymes facilitate the rapid capture of substrates and direct transfer of intermediates between cascaded catalytic units, thus rationalizing their efficient catalysis. In this study, a nanoscale ordered mesoporous Ce-based metal-organic framework (OMUiO-66(Ce)) is designed as an artificial substrate channel, where MnO2 is coupled to Ce-O clusters as a super-active catalase (CAT). An in situ soft template reduction strategy is developed to deposit well-dispersed and exposed MnO2 in the mesochannels of OMUiO-66(Ce). Several synthesis parameters are optimized to minimize the particle size to ≈150 nm for efficient intracellular endocytosis. The mesochannels provide interaction guidance that not only rapidly drove H2 O2 substrates to CAT-like catalytic centers, but also seamlessly transfer H2 O2 intermediates between superoxide dismutase-like and CAT-like biocatalytic cascades. As a result, the biomimetic system exhibits high efficiency, low dosage, and long-lasting intracellular antioxidant function. Under disease-related oxidative stress, the artificial substrate channels promote the rate of the reactions catalyzed by MnO2 , which exceeds that of the reactions catalyzed by natural CAT. Based on this observation, a set of design rules for substrate channels are proposed to guide the rational design of super-active biomimetic systems.

Zr-MOFs Integrated with a Guest Capturer and a Photosensitizer for the Simultaneous Adsorption and Degradation of 4-Chlorophenol.

A bifunctional metal-organic framework (MOF) was successfully designed to realize the purification of 4-chlorophenol (4-CP) under simulated sunlight irradiation. Owing to the large-size mesopores of the MOF matrix NU-1000, ß-CMCD (carboxylic ß-cyclodextrin) could be incorporated into the frameworks with a density of 2.4% to pre-enrich the pollutant of 4-CP. Meanwhile, the photodegradation promoter [Pd(II) meso-tetra(4-carboxyphenyl)porphine] was in situ co-assembled with the organic ligand to realize its synchronous degradation. As for the current integrator, a Langmuir model was used to explain the adsorption isotherm, and the Langmuir-Hinshelwood model exhibited a better fit to its catalytic degradation behavior. Thanks to the simultaneous presence of a capturer and a photodegradation promoter, the adsorption capacity of 4-CP reached as high as 296 mg g-1, which was further completely detoxified within 60 min under simulated sunlight irradiation with a half-life time of only 5.98 min. Such excellent integrated decontamination properties prefigure the great promising potential of multifunctional MOFs in the field of pollution purification.

Switchable Ionic Transportation in the Nanochannels of the MOFs Triggered by Light and pH.

The construction of a biomimetic ionic channel is of great significance for the fabrication of smart biodevices or logic circuit. Inspired by the selective permeability of the cell membrane toward bioions, a light-induced and pH-modulated artificial nanochannel is herein prepared by integrating the multistimuli-response molecule of carboxylated spiropyran (SP-COOH) into the frameworks of NU-1000 (Zr-based MOFs defined by Northwestern University). The loading density of the SP-COOH could reach as high as 7 wt % while keeping unchanged crystallinity and high porosity. Thanks to the precise matching of pore size of NU-1000 and molecular dimensions of SP-COOH, the loaded molecules could proceed free and reversible for isomerization between the hydrophilic and hydrophobic states. The ion-switchable characteristics of the channel are implemented by the amphiphilic change of the light-controlled gate molecule. Additionally, in the hydrophilic state, the channel presents reversible affinity toward cations or anions due to the reverse charge state induced by pH, thus constructing a pH-controlled subgate. Taking [Ru(NH3)6]3+ and [Fe(NH3)]3- as the model cation and anion, their redox peak currents occur as reversible change under different signal combinations of light and pH. Moreover, in accordance with the ionic selective permeability, several logic circuits/devices are designed to display the relationships between exogenous stimuli and ionic transportations in a computer language, prefiguring their wide application prospects in electronic devices and life sciences.

Intrinsic Apyrase-Like Activity of Cerium-Based Metal-Organic Frameworks (MOFs): Dephosphorylation of Adenosine Tri- and Diphosphate.

Apyrase is an important family of extracellular enzymes that catalyse the hydrolysis of high-energy phosphate bonds (HEPBs) in ATP and ADP, thereby modulating many physiological processes and driving life activities. Herein, we report an unexpected discovery that cerium-based metal-organic frameworks (Ce-MOFs) of UiO-66(Ce) have intrinsic apyrase-like activity for ATP/ADP-related physiological processes. The abundant CeIII /CeIV couple sites of Ce-MOFs endow them with the ability to selectively catalyse the hydrolysis of HEPBs of ATP and ADP under physiological conditions. Compared to natural enzymes, they could resist extreme pH and temperature, and present a broad range of working conditions. Based on this finding, a significant inhibitory effect on ADP-induced platelet aggregation was observed upon exposing the platelet-rich plasma (PRP) to the biomimetic UiO-66(Ce) films, prefiguring their wide application potentials in medicine and biotechnology.

Ordered Large-Pore MesoMOFs Based on Synergistic Effects of TriBlock Polymer and Hofmeister Ion.

Ordered mesoporous metal-organic frameworks (mesoMOFs) were constructed with a uniform pore size up to about 10 nm and thick microporous walls, opening up the possibility for the mass diffusion of large-size molecules through crystalline MOFs. The synergistic effects based on triblock copolymer templates and the Hofmeister salting-in anions promote the nucleation of stable MOFs in aqueous phase and the in situ crystallization of MOFs around templates, rendering the generation of a microcrystal with periodically arranged large mesopores. The improved mass transfer benefiting from large-pore channels, together with robust microporous crystalline structure, endows them as an ideal nanoreactor for the highly efficient digestion of various biogenic proteins. This strategy could set a guideline for the rational design of new ordered large-pore mesoMOFs with a variety of compositions and functionalities and pave a way for their potential applications with biomacromolecules.

Metal-Organic Frameworks Bearing Dense Alkyl Thiol for the Efficient Degradation and Concomitant Removal of Toxic Cr(VI).

Highly efficient removal of toxic Cr(VI) from aqueous media remains a crucial concern for ecosystem protection and public health. Herein, we demonstrated a new approach to solve this issue by constructing alkyl thiol-containing Zr-based metal-organic framework (MOF) adsorbents using simple and inexpensive mercaptosuccinic acid (MSA) and meso-dimercaptosuccinic acid (DMSA) as ligands. These chemically stable MOFs could be prepared in an uncomplicated, green, cost-effective, and scalable way. The interaction mechanism between alkyl thiol groups in MOFs and Cr(VI) was investigated in detail. Thanks to the formation of a Cr(VI)-thiolate complex and the oxidation of thiol groups, these designed MOFs not only exhibited high Cr(VI) adsorption capacities (202.0 and 138.7 mg/g for Zr-MSA and Zr-DMSA, respectively) but also displayed the immobilization ability for concomitant resultant Cr(III). Even in the presence of high concentrations of possibly coexistent interfering ions, the thiol-containing MOFs can still work effectively to decontaminate the Cr(VI) species. In addition, the strategy of introducing thiol groups into MOFs for Cr(VI) reduction and concomitant Cr(III) immobilization is universal for other MOFs, as verified by thiol-containing UiO-66 and MOF-808 prepared by a one-pot method. Therefore, our work not only produces several effective Cr(VI) adsorbents but also sets a general guideline for the construction of Cr(VI) adsorbents by introducing thiol groups into porous materials.

Hierarchical Porous Zr-Based MOFs Synthesized by a Facile Monocarboxylic Acid Etching Strategy.

A new monocarboxylic acid etching (MAE) strategy was developed for transforming chemically stable Zr-based metal-organic frameworks (MOFs) of UiO-66 to their hierarchical porous counterpart. The key design element was based on the incomplete replacement of bridging ligands in MOFs by monocarboxylic acids (MAs), leading to the departure of partial ligands and metal clusters to create mesopores in MOFs. A series of MAs with different acidity and carbon chain length were tested, and propionic acid (PA) was screened to be the suitable choice. The textural features including pore size distribution, specific surface area, and pore volume of the obtained products can be controlled by adjusting the MA concentration and reaction temperature. The obtained hierarchical porous MOFs inherited excellent stability from their parent materials. Additionally, the MAE strategy was universal to construct hierarchical porous Zr-based MOFs, and it was expanded to etch UiO-66 derivatives. The excellent adsorption behavior of the resultant hierarchical porous Zr-based MOFs over two enzymes with different size was also successfully exemplified, demonstrating their application potentials with bulky molecules involved.

Synthesis of a Pillar[5]arene-Based Polyrotaxane for Enhancing the Drug Loading Capacity of PCL-Based Supramolecular Amphiphile as an Excellent Drug Delivery Platform.

A pillar[5]arene-based nonionic polyrotaxane (PR) with star-poly(ε-caprolactone) ( S-PCL) as the axle, pillar[5]arene (DEP5) as the wheel and adamantane as the end-capped group is designed and synthesized. The resulting PR is subsequently assembled with ß-cyclodextrin end-capped pH-stimulated poly(acrylic acid) (CD-PAA) via a host-guest interaction to form the supramolecular pseudoblock polymer PR-PAA. This supramolecular pseudoblock polymer could self-assemble in aqueous solution to produce PR-PAA-based supramolecular vesicular nanoparticles (PR-SVNPs), which present significantly enhanced drug loading capacity (DLC, 45.6%) of DOX, much higher than those of superamphiphiles (PCL-PAA, 17.1%). Such a high DLC of PR-SVNPs can be most probably attributed to the greatly decreased crystallinity of PCL in PR. Moreover, the loaded drugs could be selectively released in an acidic microenvironment-responsive manner. Compared to free DOX, the DOX-loaded PR-SVNPs (DOX@PR-SVNPs) shows much enhanced cellular uptake and cytotoxicity against the SMMC-7721. More importantly, thanks to the enhanced permeability and retention (EPR) effect, DOX@PR-SVNPs exhibits appealing features such as extremely low toxicity, highly efficient intratumoral accumulation and substantial antitumor efficacy in vivo.

Aqueous-Phase Synthesis of Mesoporous Zr-Based MOFs Templated by Amphoteric Surfactants.

Zr-based mesoporous metal-organic frameworks (mesoMOFs) with uniform mesochannels and crystallized microporous framework were constructed in a water-based system using amphoteric surfactants as templates. Aqueous-phase synthesis guaranteed the formation of rod-shaped surfactant micelles. Meanwhile, the carboxylate groups of amphoteric surfactants provided the anchoring to bridge Zr-oxo clusters and surfactant assemblies. As a result, the directed crystallization of MOFs proceeded around cylindrical micelles and the hierarchical micro- and mesostructure was produced. The dimensions of mesopores were easily tailored by changing the alkyl chain length of the applied surfactants. The included surfactant was effectively extracted thanks to the exceptional stability of the obtained Zr-based mesoMOFs. The almost complete occupation of the mesopore by cytochrome c exemplifies the accessibility of the mesochannels, suggesting the potential applications of the obtained mesoMOFs with bulky molecules.

Simultaneous Degradation and Removal of CrVI from Aqueous Solution with Zr-Based Metal-Organic Frameworks Bearing Inherent Reductive Sites.

Given the serious harm of CrVI to human health, development of efficient techniques for its degradation and subsequent in situ adsorptive removal is highly desirable. Herein, UiO-66 type metal-organic frameworks (MOFs) integrated with various hydroxyl groups (UiO-66, UiO-66-OH, and UiO-66-(OH)2 ) were successfully explored for the efficient decontamination of CrVI from aqueous solution. The abundant hydroxyl groups in organic ligands not only served as reductive sites for the degradation of CrVI to less toxic CrIII but also acted as inherent anchorages for the efficient capture of CrIII . Thanks to their inherent hydroxyl groups and high porosity, UiO-66-(OH)2 presented almost complete removal of Cr species in simulated industrial wastewater. The total Cr content could be reduced from 5 ppm to 48 ppb under optimized adsorption conditions, which is much lower than the limits of total Cr in drinking water established by the US Environmental Protection Agency (EPA). These outstanding CrVI decontamination features, combined with the exceptional chemical stability as well as high porosity prefigured the great potentials of the current adsorbents for the remediation of real-world CrVI -containing industrial wastewater.

Synthesis of gold Nanoshells through Improved Seed-Mediated Growth Approach: Brust-like, in Situ Seed Formation.

Gold nanoshells have shown great potentials in various fields. However, the widely used seed-mediated growth method based on a silica template for gold nanoshells is a complex and time-consuming procedure. In this work, mercaptosilica was first used as a template to synthesize gold nanoshells through improved seed-mediated growth method. It is verified that gold seeds were formed and attached onto the mercaptosilica nanospheres through Brust-like, in situ process, which makes this method extremely time-saving and easy to manipulate. Importantly, the key factors affecting the in situ process were demonstrated, allowing fine control on the synthesis in a highly reproducible manner. The as-synthesized nanoshells are monodisperse with well-defined morphology and tunable near-IR plasmon resonance. Furthermore, other metal nanoparticles such as Pt and Pd could be grafted onto the surface of mercaptosilica nanospheres through the same Brust-like, in situ process. These provide new insights into seed attachment, and the improved seed-mediated growth approach based on Brust-like, in situ seed formation will take an important step forward toward the widespread application of gold nanoshells.

Controlled synthesis of multilayered gold nanoshells for enhanced photothermal therapy and SERS detection.

It can be streamlined: A facile and controllable approach for the fabrication of core/shell-structured multilayer gold nanoshells with uniform nanosize, monodispersity, and tunable plasmonic properties has been successfully developed by utilizing an organosilica layer as the dielectric spacer layer.

Hofmeister Effect Promoted the Introduction of Tunable Large Mesopores in MOFs at Low Temperature for Femtomolar ALP Detection.

In addressing the demand for hierarchically mesoporous metal-organic frameworks (HMMOFs) with adjustable large mesopores, a method based on the synergistic effects of low-temperature microemulsions and Hofmeister ions is developed. Low temperature dramatically enhanced the solubility of hydrophobic solvent in the microemulsion core, enlarging the mesopores in HMMOFs replica. Meanwhile, Hofmeister salt-in ions continuously controlled mesopore expansion by modulating the permeability of swelling agent into the microemulsion core. The large mesopores up to 33 nm provided sufficient space for the alkaline phosphatase (ALP) enrichment, and retained the remaining channel to facilitate the free mass diffusion. Leveraging these advantages, a colorimetric sensor is successfully developed using large-mesopore HMMOFs for femtomolar ALP detection based on the enrichment and cycling amplification principles. The sensor exhibited a linear detection range of 100 to 7500 fm and a limit of detection of 42 fm, presenting over 4000 times higher sensitivity than classic para-nitrophenyl phosphate colorimetric methods. Such high sensitivity highlights the importance of adjustable mesoporous structures of HMMOFs in advanced sensing applications, and prefigures their potential for detecting large biomolecules in diagnostics and biomedical research.

A simple route to prepare monodisperse Au NP-decorated, dye-doped, superparamagnetic nanocomposites for optical, MR, and CT trimodal imaging.

Monodisperse and uniform AuNP-decorated, dye-doped, superparamagnetic nanocomposites (Fe3 O4 @dye-hybrid@Au) are fabricated by using a simple method in which the Au NP formation and their attachment onto the core surface via S-Au covalent bonds proceeds almost simultaneously in a one-pot synthesis. The as-synthesized nanocomposites can simultaneously enhance the contrast effects for MR, CT, and cellular-sensitive optical imaging.

One-pot synthesis of mesoporous silica nanocarriers with tunable particle sizes and pendent carboxylic groups for cisplatin delivery.

Mesoporous silica nanocarriers with tunable particle sizes and different loadings of pendent carboxylic groups were successfully prepared by a straightforward and reproducible strategy, in which carboxyethylsilanetriol sodium salt was co-condensed with tetraethoxyorthosilicate to introduce the carboxylic groups. The key in this strategy was to separate the synthesis process into two steps of the nuclei formation and particle growth. The uniform particle size and ordered structure of the synthesized nanocarriers were manifested by several techniques such as XRD, TEM, SEM, and BET. DLS measurement illustrated that nanocarriers could be well suspended in aqueous solution. The integration and content tunability of the carboxylic groups within mesoporous silica nanoparticles (MSNs) were verified by FT-IR and (29)Si NMR. The inherent carboxylic units on the obtained carboxylic group modified MSNs (MSNs-C) effectively enhanced the capture and tailored the release properties of the anticancer drug of cisplatin. The accumulation of drug in the HeLa cells was greatly enhanced due to the highly efficient platinum uptake efficiency transported by the synthesized nanocarriers. The drug encapsulated in the MSNs-C exhibited a higher antitumor activity than free cisplatin against both MCF-7 and HeLa cells.

A simple route to synthesize mesoporous ZSM-5 templated by ammonium-modified chitosan.

Uniform mesoporous zeolite ZSM-5 crystals have been successfully fabricated through a simple hydrothermal synthetic method by utilizing ammonium-modified chitosan and tetrapropylammonium hydroxide (TPAOH) as the meso- and microscale template, respectively. It was revealed that mesopores with diameters of 5-20 nm coexisted with microporous network within mesoporous ZSM-5 crystals. Ammonium-modified chitosan was demonstrated to serve as a mesoporogen, self-assembling with the zeolite precursor through strong static interactions. As expected, the prepared mesoporous ZSM-5 exhibited greatly enhanced catalytic activities compared with conventional ZSM-5 and Al-MCM-41 in reactions involving bulky molecules, such as the Claisen-Schmidt condensation of 2-hydroxyacetophenone with benzaldehyde and the esterification reaction of dodecanoic acid and 2-ethylhexanol.