Imidazolate Framework-8 Nanoparticles Research Articles

Highly efficient suppression of zincate ion crossover in zinc–air batteries using selective membrane PVA-KOH/ZIF-8 gel polymer electrolytes

Rechargeable zinc–air batteries have attracted considerable attention in the industries due to their high energy density, affordability, and safety. However, these batteries still have limitations in their lifetime because of the issue of zincate ion (Zn(OH)42−) crossover. To suppress this issue, a new PVA-KOH-based gel polymer electrolyte membrane incorporating zeolitic imidazolate framework-8 (ZIF-8) nanoparticles was developed as a selective membrane. The influence of different-sized ZIF-8 nanoparticles synthesized with three different zinc salts on thermal, physical, and electrochemical properties was investigated. The PVA-KOH/ZIF-8 membrane significantly reduced the diffusion coefficient of zincate ions to 3.27 × 10−6, 2.01 × 10−6, and 1.99 × 10−6 cm2 min−1 by the incorporation of ZIF-8, synthesized with Zn(NO3)2, Zn(OAc)2, and ZnSO4, respectively. Because of the pore apertures of ZIF-8 that are equivalent to Zn(OH)42−, the PVA-KOH/ZIF-8 selective membrane could block Zn(OH)42−and allowed OH− to pass through the membrane. Moreover, a large external hydrophilic surface was achieved by the influence of smaller-sized particles, which improved the retention of electrolytes. As a result, the ionic conductivity of the PVA-KOH/ZIF-8 membrane increased up to 164.27 mS cm−1 when added 10 wt% ZIF-8, synthesized by ZnSO4. Furthermore, this membrane showed the highest value of battery life cycle of 89 cycles at a current density 10 mA cm−2 and the discharge capacity of 396 mAh g−1. These results indicated that the development of a PVA-KOH/ZIF-8 membrane has a high potential and suitability for use as a new class of separators in rechargeable zinc–air batteries.

Eco-friendly epoxidized Eucommia ulmoides gum based composite coating with enhanced super-hydrophobicity and corrosion resistance properties

Developing a green, non-toxic, and sustainable bio-based anticorrosive coating is significant for achieving the objective of "carbon reduction". In this study, superhydrophobic multilayer coatings based on epoxidized Eucommia ulmoides gum were prepared via a layer-by-layer assembly bottom-up approach, providing comprehensive protection for mild steel. The foundational layer, comprising the epoxidized Eucommia ulmoides gum/industrial lignin composite (EEUG-EHL), exhibited commendable adhesion, impermeability, and corrosion resistance. The intermediate layer was composed of 8-hydroxyquinoline/zeolitic imidazolate framework-8 (8HQ@ZIF-8) nanoparticles, which controlled the release of 8HQ through pH responsiveness and had self-healing properties. Employing a spraying method, a top layer with micro-nanostructured consisting of a modified ZIF-8 nanoparticle was created, inspired by the micro-nano structure observed in cicada wings. The multilayer coating exhibited remarkable super-hydrophobicity (contact angle > 150°, sliding angle < 5°), chemical stability, self-cleaning properties, and anti-fouling properties. Notably, the multilayer coating demonstrated exceptional corrosion resistance, maintaining an impedance modulus of 108 ohm cm2 (at 0.01 Hz) after immersion in a 3.5 wt% NaCl solution for 45 days. This work introduces a novel approach to enhance the corrosion protection of metal equipment, aligning with the "green development" strategy and holding significance in advancing marine anti-corrosion construction.

Multifunctional fucoidan-loaded Zn-MOF-encapsulated microneedles for MRSA-infected wound healing

Infected wound healing remains a challenging task in clinical practice due to several factors: (I) drug-resistant infections caused by various pathogens, (II) persistent inflammation that hinders tissue regeneration and (III) the ability of pathogens to persist intracellularly and evade antibiotic treatment. Microneedle patches (MNs), recognized for their effecacious and painless subcutaneous drug delivery, could greatly enhance wound healing if integrated with antibacterial functionality and tissue regenerative potential. A multifunctional agent with subcellular targeting capability and contained novel antibacterial components, upon loading onto MNs, could yield excellent therapeutic effects on wound infections. In this study, we sythesised a zeolitic imidazolate framework-8 nanoparticles (ZIF-8 NPs) loaded with low molecular weight fucoidan (Fu) and further coating by hyaluronic acid (HA), obtained a multifunctional HAZ@Fu NPs, which could hinders Methicillin-resistant Staphylococcus aureus (MRSA) growth and promotes M2 polarization in macrophages. We mixed HAZ@Fu NPs with photocrosslinked gelatin methacryloyl (GelMA) and loaded it into the tips of the MNs (HAZ@Fu MNs), administered to mice model with MRSA-infected full-thickness cutaneous wounds. MNs are able to penetrate the skin barrier, delivering HAZ@Fu NPs into the dermal layer. Since cells within infected tissues extensively express the HA receptor CD44, we also confirmed the HA endows the nanoparticles with the ability to target MRSA in subcellular level. In vitro and in vivo murine studies have demonstrated that MNs are capable of delivering HAZ@Fu NPs deep into the dermal layers. And facilitated by the HA coating, HAZ@Fu NPs could target MRSA surviving at the subcellular level. The effective components, such as zinc ions, Fu, and hyaluronic acid could sustainably released, which contributes to antibacterial activity, mitigates inflammation, promotes epithelial regeneration and fosters neovascularization. Through the RNA sequencing of macrophages post co-culture with HAZ@Fu, the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis reveals that the biological functionalities associated with wound healing could potentially be facilitated through the PI3K-Akt pathway. The results indicate that the synergistic application of HAZ@Fu NPs with biodegradable MNs may serve as a significant adjunct in the treatment of infected wounds. The intricate mechanisms driving its biological effects merit further investigation.

Preparation of stable multilayer PDMS composite pervaporation membrane incorporated with in-situ transformed metal organic frameworks for enhanced butanol recovery

In this study, stable and non-defective multilayer polydimethylsiloxane (PDMS) composite pervaporation mixed matrix membranes incorporated with in-situ transformed metal organic frameworks was successfully synthesized via ligand vapor phase infiltration and spin-coating. Metal zinc sources were uniformly distributed in PDMS which were in-situ transformed into homogeneous zeolitic imidazolate framework-8 (ZIF-8) nanoparticles, effectively alleviating the aggregation of ZIF-8. Thermal cross-linking of PDMS and the formation of MOFs occurred simultaneously, omitting the complicated preparation and re-dispersion steps of MOF nanoparticles. MOF nanoparticles and PDMS formed a more stabilized composite structure by in-situ transformation, in which PDMS and metal of MOFs can interact with the -Si-O- of silane coupling groups on membrane surface to construct solid multilayer composite membrane, ensuring long-term stability. Moreover, with the aid of hydrophobic interlayer, polymer infiltration into channels of substrate was restricted and casting solution spread out smoothly, facilitating the formation of defect-free PDMS selective layer. Various techniques including Attenuated Total Reflection-Fourier Transform Infrared Spectrometer, Field Emission Scanning Electron Microscopy, Atomic Force Microscope and X-ray Diffraction were applied to explore the morphology, composition and structure of nanoparticles and membranes, and pervaporation tests were taken to investigate the behavior of hydrophobic polymer-based multilayer membranes. For the recovery of low concentration n-butanol, the prepared non-defective multilayer TAO/ZIF-8/K-PDMS composite membrane displayed excellently total permeate flux of 2890 g m−2 h−1 with competitive separation factor of 40.3.

Construction of ternary Ni2P/ZIF-8/CdS composite for efficient photocatalytic hydrogen production and pollutant degradation: Accelerating separation of photogenerated carriers

Constructing heterojunctions for efficient charge separation is a crucial method to boost photocatalytic activity. Initially, zeolitic imidazolate framework-8 (ZIF-8) nanoparticles were synthesized in situ on the surface of cadmium sulfide (CdS) nanoflowers, creating a novel ZIF-8/CdS composite material. Subsequently, a ternary Ni2P/ZIF-8/CdS composite was fabricated for photocatalytic hydrogen production and pollution reduction. The optimally obtained Ni2P/ZIF-8/CdS composites showed excellent photocatalytic efficiency and structural stability under simulated solar light irradiation. The hydrogen production rate of Ni2P/ZIF-8/CdS composite was 21.05 mmol h−1 g−1. Additionally, Ni2P/ZIF-8/CdS degraded malachite green (MG) with 99% efficiency. It was found that the proximity of sulfides to porous MOFs accelerated the separation of light-induced charges. Nickel phosphide (Ni2P) played a vital role in photocatalytic reactions, serving the dual function of capturing photogenerated electrons and accelerating separation of photogenerated carriers. Mechanistic and characterization studies revealed that constructing heterojunction between CdS and ZIF-8 could promote photogenerated carrier transport, enhance the separation efficiency of photogenerated carriers, ultimately improving the photocatalytic hydrogen production performance and degradation efficiency.

Biologically produced and metal-organic framework delivered dual-cut CRISPR/Cas9 system for efficient gene editing and sensitized cancer therapy

Manipulation of the lactate metabolism is an efficient way for cancer treatment given its involvement in cancer development, metastasis, and immune escape. However, most of the inhibitors of lactate transport carriers suffer from poor specificity. Herein, we use the CRISPR/Cas9 system to precisely downregulate the monocarboxylate carrier 1 (MCT1) expression. To avoid the self-repairing during the gene editing process, a dual-Cas9 ribonucleoproteins (duRNPs) system is generated using the biological fermentation method and delivered into cells by the zeolitic imidazolate framework-8 (ZIF-8) nanoparticles, enabling precise removal of a specific DNA fragment from the genome. For efficient cancer therapy, a specific glucose transporter 1 inhibitor (BAY-876) is co-delivered with the duRNPs, forming BAY/duRNPs@ZIF-8 nanoparticle. ZIF-8 nanoparticles can deliver the duRNPs into cells within 1 h, which efficiently downregulates the MCT1 expression, and prohibits lactate influx. Through simultaneous inhibition of the lactate and glucose influx, BAY/duRNPs@ZIF-8 prohibits ATP generation, arrests cell cycle, inhibits cell proliferation, and finally induces cellular apoptosis both in vitro and in vivo. Consequently, we demonstrate that the biologically produced duRNPs delivered into cells by the nonviral ZIF-8 carrier have expanded the CRISPR/Cas gene editing toolbox and elevated the gene editing efficiency, which will promote biological studies and clinical applications. Statement of significanceThe CRISPR/Cas9 system, widely used as an efficient gene editing tool, faces a challenge due to cells’ ability to self-repair. To address this issue, a strategy involving dual-cutting of the genome DNA has been designed and implemented. This strategy utilizes biologically produced dual-ribonucleoproteins delivered by a metal-organic framework. The effectiveness of this dual-cut CRISPR-Cas9 system has been demonstrated through a therapeutic approach targeting the simultaneous inhibition of lactate and glucose influx in cancer cells. The utilization of the dual-cut gene editing strategy has provided valuable insights into gene editing and expanded the toolbox of the CRISPR/Cas-based gene editing system. It has the potential to enable more efficient and precise manipulation of specific protein expression in the future.

Mild low-temperature photothermal therapy demonstrated a distinctive 'hot spring' effect in the multichannel regulation of atherosclerosis instead of inducing foam cell apoptosis

Atherosclerosis (AS), characterized by endothelial injury, progressive inflammation, and lipid deposition, can cause adverse cardiovascular events. However, effectively addressing all these pathological conditions simultaneously is challenging. To devise a comprehensive treatment strategy for AS, we developed a nanoparticle-based mild photothermal therapy (PTT) approach, which controlled the temperature within the range of 42–45 ℃, creating a unique 'hot spring' effect. The nanoparticles used in this therapy consist of a core made of zeolitic imidazolate framework-8 (ZIF-8) nanoparticles loaded with indocyanine green (IR820), and an outer shell made of L-arginine (LA)-modified polydopamine (PDA), which is further modified with hyaluronic acid (HA) to target plaques. In vitro studies have demonstrated that mild PTT can open the TRPV1 channel in foam cells and regulate lipid metabolic diseases by maintaining a controlled temperature range of 42–45 ℃. Furthermore, the LA-PDA shell has anti-inflammatory properties, decreasing NLRP3 expression. Moreover, the eNOS/NO pathway was activated by LA, promoting the healing of injured endothelial cells (ECs). Additionally, the increased temperature enhances HSP90 expression, thereby helping to maintain eNOS. In vivo studies further confirmed that the HLPIZ-guided ‘hot spring’ effect has impressive anti-atherosclerotic capability by scavenging lipids, reducing inflammation, and repairing injured ECs simultaneously. In conclusion, our study confirmed that HLPIZ-guided mild PTT can exhibit a ‘hot spring’ effect, effectively regulating three key pathophysiological processes of AS, being a novel, potentially effective strategy for anti-AS therapy.

Ultrathin nitrogen-doped carbon Ti3C2Tx-TiN heterostructure derived from ZIF-8 nanoparticles sandwiched MXene for high-performance capacitive deionization

Rational design of high-performance electrode materials is crucial for enhancing desalination performance of capacitive deionization (CDI). Here, ultrathin nitrogen-doped carbon/Ti3C2Tx-TiN (NC/MX-TiN) heterostructure was developed by pyrolyzing zeolite imidazolate framework-8 (ZIF-8) nanoparticles sandwiched MXene (ZSM), which were formed by assembling ultrafine ZIF-8 nanoparticles with size of 20 nm on both sides of MXene nanosheets. The introduction of ultrasmall ZIF-8 particles allowed for in situ nitridation of the MXene during pyrolysis, forming consecutive TiN layers tightly connected to the internal MXene. The two-dimensional (2D) heterostructure exhibited remarkable properties, including high specific surface area and excellent conductivity. Additionally, the resulting TiN demonstrated exceptional redox capability, which significantly enhanced the performance of CDI and ensured cycling stability. Benefiting from these advantages, the NC/MX-TiN exhibited a maximum adsorption capacity of 45.6 mg g−1 and a steady cycling performance in oxygenated saline water over 50 cycles. This work explores the rational design and construction of MXene-based 2D heterostructure and broadens new horizons for the development of novel CDI electrode materials.

Development of an electrochemical sensitive aptasensor based on a zeolite imidazolate framework-8 and gold nanoparticles for the determination of Staphylococcus aureus bacteria.

Staphylococcus aureus (S. aureus) is one of the most important pathogens that cause illness and food poisoning. In this research, using a glassy carbon electrode (GCE)modified with zeolite imidazolate framework-8 (ZIF 8) and gold nanoparticles (AuNPs), a sensitive electrochemical aptasensor has been made for the detection of the S. aureus bacteria. The morphology of the prepared AuNPs-ZIF 8 nanocomposite has been carefully characterized by means of transmission electron microscopy (TEM), field emission scanning electron microscopy (FESEM), and energy-dispersive X-ray spectroscopy (EDS). In the manufacturing process, the S. aureus aptamer is immobilized on the AuNPs-ZIF 8 surface. Electrochemical impedance spectroscopy (EIS) method has been used for quantitative determination of S. aureus bacteria. The changes in the charge transfer resistance (Rct) of the aptamer due to the change in the concentration of bacteria are consideredas theanalytical signals. The proposed aptasensor has linear response in the concentration range of 1.5 × 101 to 1.5 × 107CFUmL-1 of S. aureus bacteria. The detection limit of the method is 3.4CFUmL-1. Using the developed aptasensor, it is possible to determine S. aureus bacteria in water and milk samples.

A new era in cancer treatment: harnessing ZIF-8 nanoparticles for PD-1 inhibitor delivery.

This review delves into the potential of zeolitic imidazolate framework-8 (ZIF-8) nanoparticles in augmenting the efficacy of cancer immunotherapy, with a special focus on the delivery of programmed cell death receptor 1 (PD-1) inhibitors. The multifunctional nature of ZIF-8 nanoparticles as drug carriers is emphasized, with their ability to encapsulate a range of therapeutic agents, including PD-1 inhibitors, and facilitate their targeted delivery to tumor locations. By manipulating the pore size and surface characteristics of ZIF-8 nanoparticles, controlled drug release can be realized. The strategic use of ZIF-8 nanoparticles to deliver PD-1 inhibitors presents a precise and targeted modality for cancer treatment, reducing off-target impacts and enhancing therapeutic effectiveness. This combined strategy addresses the existing challenges and constraints of current immunotherapy techniques, with the ultimate goal of enhancing patient outcomes in cancer therapy.

Electrospun polycaprolactone/gelatin mat incorporated with glucosamine-loaded zeolite imidazolate framework-8 nanoparticles for cartilage tissue engineering

Electrospun polycaprolactone/gelatin mat incorporated with glucosamine-loaded zeolite imidazolate framework-8 nanoparticles for cartilage tissue engineering

Acute toxicity of nanoscale zeolitic imidazolate framework 8 (ZIF-8) to saltwater planktonic species Artemia salina and Nannochloropsis oculata.

Zeolitic imidazolate framework-8 nanoparticles (ZIF-8 NPs) are metal-organic frameworks (MOFs) that have gained significant attention in various fields due to their unique properties. They have potential applications in drug delivery, gas storage, and catalysis. However, their increasing use raises concerns about their potential environmental impact. Our study evaluates the effects of ≈90nm ZIF-8 NPs in two planktonic species, the green microalga Nannochloropsis oculata and the brine shrimp Artemia salina. After synthesis and characterization (SEM, EDS, BET, and DLS) of nanoporous ZIF-8 NPs, a growth inhibition test on microalgae (72h) and acute immobilization test on instar I and II of Artemia nauplii (48h) were conducted following, OECD 201 and ISO/TS 20787, respectively. The toxicity of ZIF-8 NPs to both species was time- and concentration-dependent. The 72-h median inhibitory concentration (IC50) of ZIF-8 NPs for N. oculata based on average specific growth rate and yield were calculated as 79.71 ± 8.55mg L-1 and 51.73 ± 5.16mg L-1, respectively. Also, the 48-h median effective concentration (EC50) of ZIF-8 NPs on immobilization rate of instar I and II were calculated as 175.09 ± 4.14mg L-1 and 4.69 ± 0.34mg L-1, respectively. Moreover, the swimming type of non-immobilized animals was affected by ZIF-8 NPs. These findings provide a good insight into the toxicity of nanoparticulate ZIF-8 to saltwater planktons and also confirm that instar II Artemia is more sensitive than instar I. This study demonstrated that ZIF-8 NPs, despite all their advantages, could have toxic effects on aquatic organisms. More studies are required to assess their potential environmental impact and develop strategies to mitigate their toxicity.

A versatile polyphenol-coordinated eco-friendly hollow ZIF-based nanohybrid for precise fungicide delivery and highly efficient suppression of Botrytis cinerea

Considerable attention has been focused on the development of smart and environmentally friendly nano-pesticides that can respond to environmental stimuli, to enhance pesticide utilization while mitigating environmental risks. In this study, boscalid (Bos), a potent fungicide, was loaded into hollow zeolitic imidazolate framework-8 nanoparticles (HZNs) and coordinated with tannic acid (TA) to fabricate a pH-responsive nanohybrid platform (Bos@HZNs@TA). Results demonstrated that the HZNs@TA carriers possessed a distinct rhombic dodecahedral morphology and enhanced hydrophilic properties. The loading capacity of Bos in HZNs@TA was approximately 38.43%. Bos@HZNs@TA exhibited excellent adhesion to tomato leaves and washout resistance. Notably, the release amount of Bos from Bos@HZNs@TA at pH = 5.5 reached 84.6%, which was higher than that at neutral pH conditions for 72 h. The pH-responsive release characteristics of Bos@HZNs@TA was advantageous for its response to the acidic microenvironment created by Botrytis cinerea (B. cinerea). Additionally, Bos@HZNs@TA demonstrated exceptional effectiveness in controlling B. cinerea, surpassing the commercial Bos suspension concentrate. Importantly, Bos@HZNs@TA had no discernible adverse effects on the three non-target organisms, implying a good biocompatibility. This study provides a smart, eco-friendly, and sustainable approach to control B. cinerea effectively for plant protection.

Near-infrared light and pH-responsive hyaluronic acid-enveloped ZIF-8 nanoparticles for the treatment of pneumonia caused by methicillin-resistant Staphylococcus aureus

There is a serious threat to public health posed by the rapid spread of methicillin-resistant Staphylococcus aureus (MRSA). Photodynamic sterilization is the most effective method of combating bacterial infection, especially multidrug-resistant bacterial infection. In this study, zeolitic imidazolate framework-8 (ZIF-8) nanoparticles, one of the most attractive metal–organic framework material, were used to encapsulate the indocyanine green (ICG, a potent PS); after that, hyaluronic acid (HA) coating was applied to the nanoparticle to create a host cell-tracking nanoplatform (ICG@ZIF-8/HA). Upon near-infrared light irradiation, ICG@ZIF-8/HA exhibit excellent efficacy in producing reactive oxygen species (ROS) and killing multidrug-resistant bacteria in vitro. After the tail vein injection, ICG@ZIF-8/HA can precisely deliver to lung infection sites, and display an effective PDT-based elimination of multidrug-resistant bacteria in mouse lung infection models. These results suggest that the ICG@ZIF-8/HA nanoplatform may exhibit potent curative effects on infectious diseases.

Hierarchical porous tannic-acid-modified MOFs/alginate particles with synergized adsorption-photocatalysis for water remediation

Organic dye contaminants pose increasing threats to water ecological systems and global sustainability. Rational development of functional particles with adsorption-catalysis synergy is envisioned as a powerful route for enhanced water remediation. Here, hierarchical porous MOF-integrated alginate particles with synergized adsorption and photocatalytic degradation is developed for effective water remediation. The particles exhibit unique mesh-like Ca-alginate (CaAlg) networks with incorporated macro-/micro-porous zeolitic imidazolate framework-8 (ZIF-8) nanoparticles, both modified with negatively-charged tannic acid (TA). The TA-modified mesh-like CaAlg (CaAlg@TA) networks serve as highly porous absorbents, while the TA-modified ZIF-8 (ZIF-8@TA) nanoparticles serve as both hierarchical porous nano-absorbents and photoactive nano-catalysts. This combination simultaneously harnesses the advantages of CaAlg@TA networks and ZIF-8@TA nanoparticles to achieve adsorption-photocatalysis synergy for efficient water remediation. As demonstrated by removal of toxic and carcinogenic dye methylene blue (MB), these particles show much higher performances with fast adsorption and high capacity (1277 mg g−1), as compared to control group particles without adsorption-photocatalysis synergy. Meanwhile, the adsorption-photocatalysis synergy largely suppresses undesired secondary water contamination from the MB-adsorbed particles, and benefits particle regeneration to achieve good reusability for repeated MB removal (>95.5 % for 10 cycles). This work provides a simple and flexible route for rational fabrication of MOF-integrated particles with adsorption-photocatalysis synergy, and thus may open up new horizons for developing advanced functional particles for effective water remediation.

Metal-Organic Framework-Based Insecticide and dsRNA Codelivery System for Insecticide Resistance Management.

Targeted silencing of resistance-associated genes by specific double-stranded RNA (dsRNA) is an attractive strategy for overcoming insecticide resistance in insect pests. However, silencing target genes of insect pests by feeding on dsRNA transported via plants remains challenging. Herein, a codelivery system of insecticide and dsRNA is designed by encapsulating imidacloprid and dsNlCYP6ER1 within zeolitic imidazolate framework-8 (ZIF-8) nanoparticles to improve the susceptibility of Nilaparvata lugens (Stål) to imidacloprid. With an average particle size of 195 nm and a positive surface charge, the derived imidacloprid/dsNlCYP6ER1@ZIF-8 demonstrates good monodispersity. Survival curve results showed that the survival rates of N. lugens treated with imidacloprid and imidacloprid@ZIF-8 were 82 and 62%, respectively, whereas, in the imidacloprid/dsNlCYP6ER1@ZIF-8 treatment group, the survival rate of N. lugens is only 8%. Pot experiments demonstrate that the survival rate in the imidacloprid/dsNlCYP6ER1@ZIF-8 treatment group was much lower than that in the imidacloprid treatment group, decreasing from 54 to 24%. The identification of NlCYP6ER1 expression and the fluorescence tracking of ZIF-8 demonstrate that ZIF-8 can codeliver dsRNA and insecticide to insects via rice. Safety evaluation results showed that the dsNlCYP6ER1@ZIF-8 nanoparticle had desirable biocompatibility and biosafety to silkworm. This dsRNA and insecticide codelivery system may be extended to additional insecticides with potential resistance problems in the future, greatly enhancing the development of pest resistance management.

Autophagy-amplifying nanoparticles evoke immunogenic cell death combined with anti-PD-1/PD-L1 for residual tumors immunotherapy after RFA

Incomplete radiofrequency ablation (IRFA) triggers mild protective autophagy in residual tumor cells and results in an immunosuppressive microenvironment. This accelerates the recurrence of residual tumors and causes resistance to anti-PD-1/PDL1 therapy, which bringing a great clinical challenge in residual tumors immunotherapy. Mild autophagy activation can promote cancer cell survival while further amplification of autophagy contributes to immunogenic cell death (ICD). To this regard, we constructed active targeting zeolitic imidazolate framework-8 (ZIF-8) nanoparticles (NPs) loaded with STF62247 or both STF62247 and BMS202, namely STF62247@ZIF-8/PEG-FA (SZP) or STF62247-BMS202@ZIF-8/PEG-FA (SBZP) NPs. We found that SZP NPs inhibited proliferation and stimulated apoptosis of residual tumor cells exposed to sublethal heat stress in an autophagy-dependent manner. Further results discovered that SZP NPs could amplify autophagy in residual tumor cells and evoke their ICD, which dramatically boosted the maturation of dendritic cells (DCs). Through vaccination experiments, we found for the first time that vaccination with heat + SZP treatment could efficiently suppress the growth of new tumors and establish long-term immunological memory. Furthermore, SBZP NPs could remarkably promote the ICD of residual tumor cells, obviously activate the anti-tumor immune microenvironment, and significantly inhibit the growth of residual tumors. Thus, amplified autophagy coupled with anti-PD-1/PDL1 therapy is potentially a novel strategy for treating residual tumors after IRFA.Graphical

Co-delivery of pirfenidone and siRNA in ZIF-based nanoparticles for dual inhibition of hepatic stellate cell activation in liver fibrotic therapy

Hepatic fibrosis, as a destructive liver disease, occurs due to activated hepatic stellate cells (HSCs) producing excessive extracellular matrix deposition. If left untreated, it could further deteriorate into cirrhosis and hepatoma with high morbidity and mortality. Currently, to break the dilemma of poor targeting efficiency on HSCs and limited effect of monotherapy, it is urgent to explore a precise and efficient treatment against liver fibrosis. In the present work, a novel multifunctional nanoplatform based on vitamin A (VA) modified zeolitic imidazolate framework-8 (ZIF-8) nanoparticles was designed for co-delivery of chemical drug (Pirfenidone) and genetic drug (TGF-β1 siRNA) to achieve HSCs targeting mediated synergistic chemo-gene therapy against liver fibrosis. With the large specific surface area and acid-responsive degradation characteristics, ZIF-8 nanoparticles have great advantages to achieve high loading efficiency of Pirfenidone and enable acid-reactive drug release. After complexing siRNA, the prepared chemo-gene drug co-delivered nanocomplex (GP@ZIF-VL) proved excellent serum stability and effectively protected siRNA from degradation. Importantly, in vitro cell uptake and in vivo biodistribution demonstrated that VA functionalization markedly enhanced the delivery efficiency of GP@ZIF-VL nanocomplex into HSCs. As expected, GP@ZIF-VL significantly reduced extracellular matrix deposition and ameliorated hepatic fibrosis, as evidenced by decreased levels of liver enzymes in serum and a reduction in the hydroxyproline content in liver tissue. Therefore, GP@ZIF-VL nanocomplex displayed a bright future on the treatment of liver fibrosis with HSCs-targeting mediated chemo-gene synergetic therapy.

Preparation, identification, and application of PEG/ZIF-8@ Dendrobium huoshanense polysaccharide as an adjuvant to enhance immune responses

Zeolitic imidazolate framework-8 (ZIF-8) nanoparticles loaded with polysaccharides are excellent drug-delivery carriers with high loading capacity and pH sensitivity. This study describes the one-step encapsulation of Dendrobium huoshanense polysaccharides (DHP) in ZIF-8. The resultant PEG6000/ZIF-8@DHP complex exhibited drug release properties in acidic microenvironments, possessed water solubility, demonstrated high drug loading capacity, and displayed effective encapsulation. The effects of PEG6000/ZIF-8@ DHP administration on immunoregulation, antioxidant activities, and resistance against Aeromonas veronii in channel catfish were assessed. The study revealed that the PEG6000/ZIF-8@DHP complex stimulated cellular proliferation and phagocytosis, while also inducing the production of cytokines and nitric oxide. Additionally, the complex exhibited improved antioxidant properties and increased serum lysozyme and alkaline phosphatase activities. PEG6000/ZIF-8@DHP exhibited efficacy in vivo against Aeromonas veronii infection. These results indicate that PEG6000/ZIF-8@DHP is an efficient immunostimulant and vaccine adjuvant for enhancing immunity in channel catfish.

Enzymatic hydrolysates of κ-carrageenan by κ-carrageenase-CLEA immobilized on amine-modified ZIF-8 confer hypolipidemic activity in HepG2 cells

κ-Carrageenase can degrade κ-carrageenan to produce bioactive κ-carrageenan oligosaccharides (KCOs) that have potential applications in pharmaceutical, food, agricultural, and cosmetics industries. Immobilized enzymes gain their popularity due to their good reusability, enhanced stability, and tunability. In this study, the previously characterized catalytic domain of Pseudoalteromonas purpurea κ-carrageenase was covalently immobilized on the synthesized amine-modified zeolitic imidazolate framework-8 nanoparticles with the formation of cross-linked enzyme aggregates, and the immobilized κ-carrageenase was further characterized. The immobilized κ-carrageenase demonstrated excellent pH stability and good reusability, and exhibited higher optimal reaction temperature, better thermostability, and extended storage stability compared with the free enzyme. The KCOs produced by the immobilized κ-carrageenase could significantly decrease the TC, TG, and LDL-C levels in HepG2 cells, increase the HDL-C level in HepG2 cells, and reduce the free fatty acids level in Caco-2 cells. Biochemical assays showed that the KCOs could activate AMPK activity, increase the ratios of p-AMPK/AMPK and p-ACC/ACC, and downregulate the expression of the lipid metabolism related proteins including SREBP1 and HMGCR in the hyperlipidemic HepG2 cells. This study provides a novel and effective method for immobilization of κ-carrageenase, and the KCOs produced by the immobilized enzyme could be a potential therapeutic agent to prevent hyperlipidemia.