Zeolitic Imidazolate Framework-8 Nanoparticles Research Articles

Nonflammable, robust and recyclable hydrophobic zeolitic imidazolate frameworks/sponge with high oil absorption capacity for efficient oil/water separation

Developing robust sponge-based materials with high oil capacity and excellent flame resistance for oil spill cleanup is significant. Herein, a highly hydrophobic composite sponge material for oil-water separation, containing a melamine-formaldehyde (MF) sponge substrate and zeolitic imidazolate framework-8 (ZIF-8) coating was fabricated through the simple amino-assisted in-situ growth of ZIF-8 onto the strut surface of MF sponge. The successful integration of MF sponge and ZIF-8 nanoparticles in one composite material was confirmed by scanning electron microscopy, X-ray diffraction and nitrogen sorption. The synergistic effect of the MF substrate and ZIF-8 coating significantly improved its flame resistance. Combining the advantage of the MF substrate and the hydrophobic ZIF-8 nanocrystals, the ZIF-8/MF composite sponge showed high porosity and good hydrophobicity with a water contact angle of 130°. A high adsorption capacity towards various oils was achieved in the range of 76–164 g g−1. Besides, the ZIF-8/MF composite sponge exhibited excellent separation performance for light oil/heavy oil-water mixtures via adsorption and/or gravity-driven separation. In addition, owing to its compressibility and mechanical stability, the ZIF-8/MF composite sponge could be easily regenerated by a simple squeezing method and showed excellent recyclability for the oil adsorption. These features make the ZIF-8/MF composite sponge promising for highly efficient oil-water separation.

ZIF-8 nanoparticles induce neurobehavioral disorders through the regulation of ROS-mediated oxidative stress in zebrafish embryos

Zeolite imidazolate framework-8 (ZIF-8) is a nanomaterial of metal-organic frameworks (MOFs), which have various applications in drug delivery and water pollution remediation. However, little is known about its developmental neurotoxicity in aquatic organisms, especially on the low-level exposure. In the present study, we investigated the toxic effects of ZIF-8 NPs on the neuron development, behavioral traits, oxidative stress and gene expression in zebrafish embryos. Firstly, our results showed that ZIF-8 induced significantly embryonic malformations and abnormal development of nervous system in zebrafish embryos with a concentration-dependent manner. Meanwhile, the locomotor behavior was obviously inhibited while the anxiety behavior was greatly increased after ZIF-8 exposure. Secondly, the levels of ROS and antioxidant enzyme activities (CAT, SOD and MDA) together with AChE and ATPase were substantially increased in the ZIF-8 exposed groups. At the molecular level, ZIF-8 NPs could down-regulate the expression profiles of neural development-related genes (gap43, synapsin 2a and neurogenin 1) and PD-like related genes (dj-1, dynactin and parkin), but up-regulate the expression levels of neuro-inflammatory genes (nox-1, glip1a and glip1b) in larval zebrafish. In addition, we further explored the molecular mechanism of neurotoxicity induced by ZIF-8 with pharmacological experiments. The results showed that specific inhibition of ROS-mediated oxidative stress by the astaxanthin could reverse the expression patterns of ATPase, AChE and neurodevelopmental genes. Moreover, astaxanthin can partially rescue the ZIF-8-modulated locomotor behavior. Taken together, our results demonstrated that ZIF-8 had the potential to cause neurotoxicity in zebrafish embryos. These informations presented in this study will help to elucidate the molecular mechanisms of ZIF-8 nanoparticles exposure in zebrafish, which providing a scientific evaluation of its safety to aquatic ecosystems.

Buffet-style Cu(II) for enhance disulfiram-based cancer therapy

Studies have shown that disulfiram (DSF) can combine with Cu2+ to form bis(N, N-diethyldithiocarbamate) copper(II) complex (CuET) as antitumor drugs. However, there is insufficient endogenous Cu2+ dose to eradicate cancer cells selectively. Inspired by the buffet, we use Cu2+ doped hollow zeolitic imidazolate framework nanoparticles (HZIFCu) as the carrier and equipped with DSF and indocyanine green (ICG) and targeted by folic acid (FA) (D&I@HZIFCu-FA) to enhance DSF-based cancer therapy. D&I@HZIFCu-FA could effectively supply Cu2+ by a buffet-style, assisting the “DSF-to-CuET” transformation in the tumor. Additionally, self-supply Cu2+ could convert H2O2 into ·OH by triggering a Fenton-like reaction for chemo-dynamic therapy, and ICG achieves photothermal therapy for tumors under laser irradiation. This work provides a buffet-style for Cu2+ to make DSF a strong candidate for cancer treatment by combining chemotherapy, chemo-dynamic therapy, and photothermal therapy and inspires more research about its applications in tumor therapy.

Microvesicle-camouflaged biomimetic nanoparticles encapsulating a metal-organic framework for targeted rheumatoid arthritis therapy

BackgroundMethotrexate (MTX) has been highlighted for Rheumatoid arthritis (RA) treatment, however, MTX does not accumulate well at inflamed sites, and long-term administration in high doses leads to severe side effects. In this study, a novel anti-RA nanoparticle complex was designed and constructed, which could improve the targeted accumulation in inflamed joints and reduce side effects.ResultsHere, we prepared a pH-sensitive biomimetic drug delivery system based on macrophage-derived microvesicle (MV)-coated zeolitic imidazolate framework-8 nanoparticles that encapsulated the drug methotrexate (hereafter MV/MTX@ZIF-8). The MV/MTX@ZIF-8 nanoparticles were further modified with 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[folate (polyethylene glycol)-2000] (hereafter FPD/MV/MTX@ZIF-8) to exploit the high affinity of folate receptor β for folic acid on the surface of activated macrophages in RA. MTX@ZIF-8 nanoparticles showed high DLE (~ 70%) and EE (~ 82%). In vitro study showed that effective drug release in an acidic environment could be achieved. Further, we confirmed the activated macrophage could uptake much more FPD/MV/MTX@ZIF-8 than inactivated cells. In vivo biodistribution experiment displayed FPD/MV/MTX@ZIF-8 nanoparticles showed the longest circulation time and best joint targeting. Furthermore, pharmacodynamic experiments confirmed that FPD/MV/MTX@ZIF-8 showed sufficient therapeutic efficacy and safety to explore clinical applications.ConclusionsThis study provides a novel approach for the development of biocompatible drug-encapsulating nanomaterials based on MV-coated metal-organic frameworks for effective RA treatment.Graphical

Stem Cell Membrane-Encapsulated Zeolitic Imidazolate Framework-8: A Targeted Nano-Platform for Osteogenic Differentiation.

Mesenchymal stem cells (MSCs) have been recognized as one of the most promising pharmaceutical multipotent cells, and a key step for their wide application is to safely and efficiently regulate their activities. Various methods have been proposed to regulate the directional differentiation of MSCs during tissue regeneration, such as nanoparticles and metal ions. Herein, nanoscale zeolitic imidazolate framework-8 (ZIF-8), a Zn-based metal-organic framework, is modified to direct MSCs toward an osteoblast lineage. Specifically, ZIF-8 nanoparticles are encapsulated using stem cell membranes (SCMs) to mimic natural molecules and improve the biocompatibility and targeted ability toward MSCs. SCM/ZIF-8 nanoparticles adjust the sustained release of Zn2+ , and promote their specific internalization toward MSCs. The internalized SCM/ZIF-8 nanoparticles show excellent biocompatibility, and increase MSCs' osteogenic potentials. Moreover, RNA-sequencing results elucidate that the activated cyclic adenosine 3,5-monophosphate (cAMP)-PKA-CREB signaling pathway can be dominant in accelerating osteogenic differentiation. In vivo, SCM/ZIF-8 nanoparticles greatly promote the formation of new bone tissue in the femoral bone defect detected by 3D micro-CT, hematoxylin and eosin staining, and Masson staining after 4 weeks. Overall, the SCM-derived ZIF-8 nanostructures achieve the superior targeting ability, biocompatibility, and enhanced osteogenesis, providing a constructive design for tissue repair.

ZIF-8 nanoparticles coated with macrophage-derived microvesicles for sustained, targeted delivery of dexamethasone to arthritic joints

Dexamethasone sodium phosphate (Dex) is widely used in the clinic for the treatment of rheumatoid arthritis. However, it circulates in the blood for a short time and it is linked to a high risk of severe side effects caused by repeated dosing. Here, we encapsulated Dex onto zeolitic imidazolate framework-8 (ZIF-8) to prepare metal–organic framework nanoparticles with high drug loading efficiency. To prevent clearance by the mononuclear phagocyte system and extend time in circulation, the nanoparticles were also camouflaged with macrophage-derived microvesicles (MV) to obtain the biomimetic drug delivery system MV/Dex/ZIF-8. In vitro and in vivo experiments showed that the nanosystem had high drug loading and encapsulation efficiency, high stability, and long circulation time, and it permitted sustained drug release longer in inflamed joint tissues. Our study provides new insights into designing camouflaged drug carriers to prevent their phagocytosis and prolong their time in circulation.

Stability of ZIF-8 Nanoparticles in Most Common Cell Culture Media.

Zeolite imidazolate framework-8 (ZIF-8) is a promising platform for drug delivery, and information regarding the stability of ZIF-8 nanoparticles in cell culture media is essential for proper interpretation of in vitro experimental results. In this work, we report a quantitative investigation of the ZIF-8 nanoparticle’s stability in most common cell culture media. To this purpose, ZIF-8 nanoparticles containing sterically shielded nitroxide probes with high resistance to reduction were synthesized and studied using electron paramagnetic resonance (EPR). The degradation of ZIF-8 in cell media was monitored by tracking the cargo leakage. It was shown that nanoparticles degrade at least partially in all studied media, although the degree of cargo leakage varies widely. We found a strong correlation between the amount of escaped cargo and total concentration of amino acids in the environment. We also established the role of individual amino acids in ZIF-8 degradation. Finally, 2-methylimidazole preliminary dissolved in cell culture media partially inhibits the degradation of ZIF-8 nanoparticles. The guidelines for choosing the proper cell culture medium for the in vitro study of ZIF-8 nanoparticles have been formulated.

Zeolitic Imidazolate Framework-8 Nanoparticles Exhibit More Severe Toxicity to the Embryo/Larvae of Zebrafish (Danio rerio) When Co-Exposed with Cetylpyridinium Chloride.

The combined application of nanoparticles and surfactants has attracted tremendous attention in basic research and industry. However, knowledge of their combined toxicity remains scarce. In this study, we exposed zebrafish embryos to cetylpyridinium chloride (CPC, a cationic surfactant, at 0 and 20 μg/L), zeolitic imidazolate framework nanoparticles (ZIF-NPs, at 0, 30, and 60 mg/L), and their mixtures until 120 h post-fertilization (hpf). Within the used concentration range, both single and combined exposures exhibited limited effects on the survival and hatching of zebrafish. However, the combined exposure of ZIF-NPs and CPC caused more severe effects on the heart rate at both 48 and 72 hpf. The combined exposure also induced significant hyperactivity (i.e., increasing the average swimming velocity) and oxidative stress in zebrafish larvae (at 120 hpf), although all single exposure treatments exhibited limited impacts. Furthermore, the level of reactive oxygen species (or malondialdehyde) exhibited a significantly positive correlation with the heart rate (or average swimming velocity) of zebrafish, suggesting that oxidative stress plays a role in mediating the combined toxicity of CPC and ZIF-NPs to zebrafish. Our findings suggest that the interaction of CPC and ZIF-NPs should not be ignored when assessing the potential risks of their mixtures.

Dual-crosslinked networks of superior stretchability and toughness polyacrylamide-carboxymethylcellulose hydrogel for delivery of alendronate

Hydrogels have been widely applied in biomedical, bionic, and intelligent devices. However, pure hydrogels suffer from poor elasticity and mechanical properties, which severely limit their application. Employing dual-crosslinked networks, comprising simultaneous existence of chemical and physical crosslinks, is an effective approach to circumvent these limitations. In this study, the zeolitic imidazolate framework-8 (ZIF-8) and alendronate loaded ZIF-8 (Aln@ZIF-8) nanoparticles were synthesized by one-pot method. Then, by incorporating ZIF-8 or Aln@ZIF-8 nanoparticles, the dual-crosslinked hydrogel consisting of hydrophilic polyacrylamide (PAM), carboxymethyl cellulose (CMC) was developed. Furthermore, the mechanical properties were measured using a universal testing machine. The results showed that the hydrogel exhibited superior tensile properties, compression properties, storage modulus (G′), and loss modulus (G″) in 10 wt% ZIF-8 nanoparticles. Therefore, considering the superior mechanical properties, the 10 wt% hydrogels were selected as promising candidates as Aln delivery carriers with a high loading capacity (63.83%) and a longer releasing profile (6 d), which might be a potential application in tissue engineering.

ZIF-8 channeled and coordination-bridging two-dimensional WS2 membrane for efficient organic solvent nanofiltration

Zeolitic imidazolate framework-8 (ZIF-8)/WS2 composite 2D membranes were constructed by in-situ growth of ZIF-8 in the interlayer of WS2 laminar membrane. The growth of ZIF-8 nanoparticles in WS2 membrane expanded the interlayer spacing, and endowed WS2 membrane with fixed interlayer spacing by coordination-bridges between WS2 and ZIF-8, which made ZIF-8/WS2 membrane possess not only high solvent permeance but also excellent stability in organic solvents. Isopropanol (IPA) permeance through ZIF-8/WS2 membrane reached 272 L/m2·h·bar, which was about 1.6 times higher than that through pristine WS2 membrane, and the rejection rates for Direct Black 38 (DB38), Congo Red (CR) and Rose Bengal (RosB) were 99%, 99% and 30% respectively. Furthermore, the IPA permeance through ZIF-8/WS2 membrane was almost unchanged after soaking in IPA for 192 h, and IPA permeance and rejection rate for DB 38 changed slightly during 100 h of cross-flow filtration, demonstrating remarkable stability of ZIF-8/WS2 membranes in organic solvents and a promising application potential in organic solvent nanofiltration.

ZIF-8 modified multifunctional injectable photopolymerizable GelMA hydrogel for the treatment of periodontitis

Periodontitis is a chronic inflammatory disease caused by plaque that leads to alveolar bone resorption. In the treatment of periodontitis, it is necessary to reduce the bacterial load and promote alveolar bone regeneration. In this study, zeolitic imidazolate framework-8 (ZIF-8) is used in the treatment of periodontitis, and an injectable photopolymerizable ZIF-8/gelatin methacryloyl (GelMA) composite hydrogel (GelMA-Z) is constructed. We confirm that ZIF-8 nanoparticles are successfully loaded into GelMA, which demonstrates fluidity and photopolymerizability. GelMA-Z continuously releases Zn2+ and shows good cytocompatibility. In vitro, GelMA-Z can effectively upregulate the expression of osteogenesis-related genes and proteins, increase alkaline phosphatase activity, promote extracellular matrix mineralization by rat bone mesenchymal stem cells, and exert an obvious antibacterial effect against Porphyromonas gingivalis. In vivo, GelMA-Z reduces the bacterial load, relieves inflammation and promotes alveolar bone regeneration in a rat model. The above results show that GelMA-Z has potential prospects in the treatment of periodontitis. Statement of significanceVarious methods have been explored for the treatment of periodontitis. However, current regiments have difficulty achieving ideal alveolar bone regeneration. In this study, we constructed a zeolitic imidazolate framework-8 (ZIF-8)/gelatin methacryloyl (GelMA) composite hydrogel (GelMA-Z). (1) The injectable and photopolymerizable GelMA-Z showed biocompatibility in vitro and in vivo. (2) GelMA-Z continually released zinc ions to promote the osteogenic differentiation of bone mesenchymal stem cells and kill bacteria in vitro. (3) In a rat model, the GelMA-Z pregel solution was used to fill the periodontal pocket and then crosslinked by UV exposure. GelMA-Z can stably remain in the periodontal pocket to reduce the bacterial load, relieve inflammation and promote alveolar bone regeneration. In conclusion, GelMA-Z has great potential for use in the treatment of periodontitis, especially in promoting alveolar bone regeneration.

Biomineralized Zeolitic Imidazolate Framework-8 Nanoparticles Enable Polymerase-Driven DNA Biocomputing for Reliable Cell Identification.

Investigating multiple miRNA expression patterns in living cells by DNA logic biocomputing is a valuable strategy for diagnosis and biomedical studies. The introduction of protein enzymes in DNA logic biocomputing circuits not only expands the toolbox of nucleic acid assembly techniques, but also further improves the specificity of recognizing and processing of DNA input. Herein, a polymerase-driven primer exchange reaction, acting as the sensing module, is introduced into the biocomputing system and transduces the multiple miRNAs sensing event into the intermediate triggers for activating the subsequent processing module, which further performs signal readout through DNAzyme catalytic substrate cleavage reaction. By using biomineralized zeolitic imidazolate framework-8 nanoparticles (ZIF-8 NPs) to deliver all the components of the biocomputing system, including polymerase and DNA probes, we realized polymerase-driven DNA biocomputing operations in living cells, including AND and OR gates. The results exhibited that biomineralized ZIF-8 NPs can protect the loaded cargoes against the external environment and deliver them efficiently to the cytoplasm. The polymerase-driven DNA biocomputing system based on multiple miRNAs sensing can be used for reliable cell identification and may provide a promising platform for more accurate diagnosis and programmable therapeutics.

Heterostructured ZIF-8/lamellar talc composites incorporated polydimethylsiloxane membrane with enhanced separation performance for butanol recovery

In this study, heterostructured MOF/lamellar talc composites was successfully synthesized by in-situ growth of zeolitic imidazolate framework-8 (ZIF-8) nanoparticles on acidified black talc (ABT) and introduced into polydimethylsiloxane (PDMS) matrix to prepare high-performance mixed matrix membranes (MMMs) via spin coating and thermal cross-linking. The submicron-size natural lamellar black talc (BT) was first explored as stable carrier to synthesize laminated composite with continuous MOF phase. Owing to its silica-oxygen tetrahedral structure, the resultant laminated composite presented good compatibility with PDMS matrix, avoiding the formation of interfacial defect between polymer and nanoparticles. Moreover, well-dispersed and continuous ZIF-8 nanoparticles on lamellar nanosheets had preferential adsorption effect for alcohol, enhancing the selectivity of membranes. The coupling effects of graphene-like lamellar structure from talc and sequential transport channels from ZIF-8 attributed to greatly enhance permeation flux. Various techniques such as FESEM, TEM, FTIR, XRD and EDS were applied to investigate the morphology and structure of composites and membranes, and pervaporation experiments were applied to probe the behavior of polymer-based composite membranes. High performance defect-free ZIF-8@ABT/PDMS MMMs exhibited excellent total permeate flux of 1711 g m−2 h−1 with very competitive separation factor of 41 for low concentration n-butanol recovery.

Synergistic modification of ZIF and silica on carbon spheres to enhance the flame retardancy of composites coatings

Herein, carbon spheres (CS) were obtained by a simple hydrothermal reaction using glucose as the raw material, which can be used as a green, cost-effective inorganic flame retardant. Then, the zeolitic imidazolate framework-8 (ZIF) nanoparticles were uniformly anchored on the surface of the CS, which could promote the formation of carbon residues, while the release of inert gas could reduce the substrate surface temperature, thereby delaying the combustion reaction. In addition, the SiO2 film was coated on the surface of ZIF-loaded CS (CS/ZIF) to fill the micropores left by thermal decomposition of ZIF nanoparticles. More importantly, the residual SiO2 shell after combustion can effectively improve the barrier effect of char layer on flame and heat. The effect of the obtained CS/ZIF@SiO2 hybrids on the fire performance of epoxy resins was characterized by fire performance tests. The experimental results showed that the backside temperature of the CS/ZIF@SiO2 based composite coating was stabilized at the lowest value (173.6 ℃) due to the combined effect of ZIF nanoparticles and silica film. In addition, the CS/ZIF@SiO2/EP showed the maximum expansion height and expansion rate after burning in a muffle furnace for 60 min. Meanwhile, the composite coating exhibited the maximum residual carbon (29.1%) and thermal decomposition temperature (Tmax, 378.1 ℃). The results of smoke density test proved that the composite coating had higher smoke suppression effect compared with other samples.

Stabilize thin nanoparticle layer of zeolitic imidazole framework-8 (ZIF-8) on different PVDF substrates by contra-diffusion method for high-efficiency ultrafiltration application

In this research, a contra-diffusion cell, which is an effective instrument for growing inorganic layers on porous substrates, was applied to prepare a thin layer of zeolitic imidazole framework-8 (ZIF-8) on polyvinylidene fluoride (PVDF) ultrafiltration membranes. With using of methanol as a solvent, a thin layer of ZIF-8 was fabricated resulted in a flexible inorganic coated organic membrane. The ZIF-8 nanoparticles were formed as a resistant layer on the outer surface and inner pores of PVDF support and its effect on permeability, flux recovery ratio (FRR) and treatment of colored wastewater was investigated. Manufacturing parameters such as the reaction time between Zn2+ ions and imidazole ligands (16, 24 and 36 h) and concentration of PVDF in the casting solution of the support membranes (18, 20 and 22 wt%) were considered. The SEM images showed the well-growing of uniform and a thin layer of ZIF-8. The membrane performance tests revealed that ZIF-8 decorated membranes have higher pure water flux, BSA protein rejection and FRR related to the uncoated PVDF membrane. The fabricated membranes indicated high removal efficiency in three different MW dyes (Rhodamine B, Reactive Green 19 and Direct Black 38), with 75, 85 and 98% rejection, respectively.

ZIF-8 Nanoparticles Based Electrochemical Sensor for Non-Enzymatic Creatinine Detection.

There is a consistent demand for developing highly sensitive, stable, cost-effective, and easy-to-fabricate creatinine sensors as creatinine is a reliable indicator of kidney and muscle-related disorders. Herein, we reported a highly sensitive and selective non-enzymatic electrochemical creatinine sensor via modifying poly(3,4 ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS) coated indium tin oxide (ITO) substrate by zeolitic imidazolate framework-8 nanoparticles (ZIF-8 NPs). The topography, crystallinity, and composition of the sensing electrode were characterized by field emission scanning electron microscopy (FESEM), atomic force microscopy (AFM), X-ray diffraction (XRD), and X-ray photoelectron spectroscopy (XPS). The peroxidase-like activity of ZIF-8 nanoparticles enabled it to detect creatinine forming a zinc-creatinine composite. The electrochemical behavior and sensing performance were evaluated by amperometric and impedimetric analysis. The sensor obtained a sufficiently low limit of detection (LOD) of 30 µM in a clinically acceptable linear range (0.05 mM–2.5 mM). The interference study demonstrated high selectivity of the sensor for creatinine concerning other similar biomolecules. The sensing performance of the creatinine sensor was verified in the actual human serum, which showed excellent recovery rates. Hence, the magnificent performance of ZIF-8 based non-enzymatic creatinine sensor validated it as a responsible entity for other complicated renal markers detection.

Desalination Characteristics of Cellulose Acetate FO Membrane Incorporated with ZIF-8 Nanoparticles.

Forward osmosis membranes have a wide range of applications in the field of water treatment. However, the application of seawater desalination is restricted, so the research of forward osmosis membranes for seawater desalination poses new challenges. In this study, zeolitic imidazolate framework-8 (ZIF-8) was synthesized by a mechanical stirring method, and its crystal structure, surface morphology, functional group characteristics, thermochemical stability, pore size distribution and specific surface area were analyzed. The cellulose acetate (CA)/ZIF-8 mixed matrix forward osmosis membrane was prepared by using the synthesized ZIF-8 as a modified additive. The effects of the additive ZIF-8 content, coagulation bath temperature, mixing temperature and heat treatment temperature on the properties of the CA/ZIF-8 forward osmosis membrane were systematically studied, and the causes were analyzed to determine the best membrane preparation parameters. The structure of the CA membrane and CA/ZIF-8 mixed matrix forward osmosis membranes prepared under the optimal conditions were characterized by Fourier Transform infrared spectroscopy (FTIR), Scanning electron microscopy (SEM), contact angle and Atomic force microscope (AFM). Finally, the properties of the HTI membrane (Membrane manufactured by Hydration Technology Innovations Inc.), CA forward osmosis membrane and CA/ZIF-8 mixed matrix forward osmosis membrane were compared under laboratory conditions. For the CA membrane, the water flux and reverse salt flux reached 48.85 L·m−2·h−1 and 3.4 g·m−2·h−1, respectively. The reverse salt flux and water flux of the CA/ZIF-8 membrane are 2.84 g·m−2·h−1 and 50.14 L·m−2·h−1, respectively. ZIF-8 has a promising application in seawater desalination.

Augmented EPR effect post IRFA to enhance the therapeutic efficacy of arsenic loaded ZIF-8 nanoparticles on residual HCC progression

BackgroundInsufficient radiofrequency ablation (IRFA) can promote the local recurrence and distal metastasis of residual hepatocellular carcinoma (HCC), which makes clinical treatment extremely challenging. In this study, the malignant transition of residual tumors after IRFA was explored. Then, arsenic-loaded zeolitic imidazolate framework-8 nanoparticles (As@ZIF-8 NPs) were constructed, and their therapeutic effect on residual tumors was studied.ResultsOur data showed that IRFA can dramatically promote the proliferation, induce the metastasis, activate the epithelial–mesenchymal transition (EMT) and accelerate the angiogenesis of residual tumors. Interestingly, we found, for the first time, that extensive angiogenesis after IRFA can augment the enhanced permeability and retention (EPR) effect and enhance the enrichment of ZIF-8 nanocarriers in residual tumors. Encouraged by this unique finding, we successfully prepared As@ZIF-8 NPs with good biocompatibility and confirmed that they were more effective than free arsenic trioxide (ATO) in sublethal heat-induced cell proliferation suppression, apoptosis induction, cell migration and invasion inhibition, and EMT reversal in vitro. Furthermore, compared with free ATO, As@ZIF-8 NPs exhibited remarkably increased therapeutic effects by repressing residual tumor growth and metastasis in vivo.ConclusionsThis work provides a new paradigm for the treatment of residual HCC after IRFA.Graphical

Tough ion gels composed of coordinatively crosslinked polymer networks using ZIF-8 nanoparticles as multifunctional crosslinkers.

Constructing crosslinked polymer networks via reversible interactions is a promising approach to recover the mechanical strength of damaged gels. In addition, by designing effective reversible crosslinks, the mechanical strength of the gel can be enhanced through energy dissipation based on the destruction of the crosslinks by an applied force. In this study, we introduced zeolitic imidazole framework-8 nanoparticles (ZIF-8 NPs), which acted as multifunctional crosslinkers, to provide multipoint coordination bonding with a poly(N,N-dimethylacrylamide)-based polymer network in a gel containing an ionic liquid. The mechanical strength of the gel increased with an increase in the content of ZIF-8 NPs up to 6 wt%. It was confirmed that the energy loaded onto the gel was dissipated through the desorption of the polymer network from the surface of the ZIF-8 NPs. Owing to the reversible destruction and reconstruction of the coordinative crosslinking between the polymer network and ZIF-8 NPs, the mechanical strength of the damaged gel was almost fully recovered through annealing.

Targeted therapy of atherosclerosis by zeolitic imidazolate framework-8 nanoparticles loaded with losartan potassium via simultaneous lipid-scavenging and anti-inflammation.

Atherosclerosis (AS) is a condition associated with dysfunctional lipid metabolism and an inflammatory immune microenvironment that remains the leading cause of severe cardiovascular events. Drugs exhibiting both anti-inflammatory and lipid-scavenging activity hold great promise for treating AS. In this study, zeolitic imidazolate framework-8 (ZIF-8) nanoparticles loaded with losartan potassium (LP) were developed as an anti-AS treatment to target both of these therapeutic arms simultaneously. LP@ZIF-8 accumulated within AS target tissues via the enhanced permeability and retention (EPR) effect, as confirmed via in vivo near-infrared fluorescence (NIRF) imaging and wasdisruptedin response tothe low pH. ZIF-8 could activate autophagy, thus regulatinglipid metabolism and restoringcholesterol homeostasis aspreviously reported, while thereleasedLPservedas an anti-inflammatory angiotensin receptor blocker (ARB) inhibitor, which was confirmed via the in vivo treatment studies. As such, our data highlight LP@ZIF-8 as a promising therapeutic agent capable of attenuating the severity of AS.