Zeolitic Imidazolate Framework Research Articles

Designing Artificial Laccase Catalysts by Introducing Substrate Oxidation Metals into Oxygen-Reducing Metal-Organic Frameworks: Cu-Doped ZIF-67.

Laccase, a multi-copper oxidase, is limited by its optimal temperature range and isolation costs. To overcome these challenges, we synthesized copper-doped zeolitic imidazolate framework-67 (Cu-doped ZIF-67) with 16 mol % Cu as an artificial laccase catalyst. The introduced Cu site acts as the phenol oxidation site, and Co-based ZIF-67 is the four-electron oxygen reduction site. Laccase also employs this division of oxidation and reduction sites. Cu-doped ZIF-67 demonstrated significant catalytic activity, superior to natural laccase, especially at elevated temperatures, and maintained stability across multiple reaction cycles. These findings suggest that Cu-doped ZIF-67 is a robust, reusable alternative for industrial applications requiring high thermal stability and efficient catalysis.

Nanobiohybrid Extracellular Vesicle Nanoreactor with Improving Metabolical Activity for Biocatalytic Therapy.

Extracellular vesicles (EVs) hosting enzymatic activities that function as independent metabolic units are attractive natural biocatalytic platforms. However, directly using these metabolically active nanoreactors for effective biocatalytic applications remains challenging, mainly due to their constrained catalytic capabilities. Here, we construct an EV-templated nanobiohybrid system by engineering an EV surface with a photoresponsive zeolitic imidazolate framework (ZIF). The deposition of ZIF nanostructures on EVs not only contributes to improved biocatalytic stability but also enables interfacial coupling between photoexcited electrons from the ZIF and the enzymatic reaction of metabolically active EVs. Nearly 300% of biomass conversion efficiency increment could be achieved by EVs derived from macrophages. This enhanced biocatalysis, high catalytic stability, and low cytotoxicity endowed the EV@ZIF nanosystem with robust biosynthesis and antimicrobial activity. When evaluated in a mouse periodontitis model, we show that the autologous biocatalytic EV@ZIF demonstrated efficient therapeutic capability by killing bacteria and inhibiting inflammation. This nanoengineering strategy will benefit the future optimization of metabolically active EV nanoreactors as biocatalysts for a broad range of therapeutics.

Atomically Tailored Zn-ZIF-8 via RuNi Nanoalloy Replacement for Improved Photocatalytic H2 Evolution.

In this study, we developed a solid-state atomic replacement method for metal catalysts, enabling the exchange of metal atoms between single atoms and nanoalloys to create new combinations of nanoalloys and single atoms. We observed that partial metal interchange occurred between the RuNi nanoalloy and Zn from the zeolitic imidazolate framework-8 (ZIF-8) on a carbon-nitrogen framework (CNF) at a high temperature of 900 °C, leading to the creation of RuZn nanoparticles and single nickel atoms (Ni-CN). Extended X-ray absorption fine structure (EXAFS) and X-ray absorption near edge structure (XANES) analyses revealed that Ni is atomically dispersed within (RuZn)/Ni-CN. This finding confirms the migration of Zn and Ni during the pyrolysis of the RuNi@ZIF-8 precursor, providing definitive evidence of atomic replacement. Due to the synergistic influence of RuZn nanocrystals and Ni-CN, the resulting (RuZn)/Ni-CN multisite catalyst exhibited superior hydrogen evolution reaction (HER) ability compared to the conventional nanoalloy-based catalysts. Density functional theory calculations revealed that the integration of the (RuZn)n cluster on Ni surrounded with different N-coordinated carbon structures enhanced HER activity with the optimized (RuZn)n/NiN2C2 catalyst exhibiting a low ΔGH and improved electron charge redistribution, thereby promoting favorable hydrogen adsorption. Our findings provide valuable insights into the design and optimization of photocatalysts through atomic-level engineering, opening new avenues for efficient and sustainable energy conversion technologies.

PH-Responsive Metal–Organic Framework for Targeted Delivery of Fungicide, Release Behavior, and Sustainable Plant Protection

A smart and environmentally friendly pesticide system was developed that could respond to environmental stimuli while mitigating environmental risks. In this study, thiabendazole (Thi), an effective fungicide, was loaded onto zeolitic imidazolate framework-8 (ZIF-8) using the impregnation method to fabricate a pH-responsive nano hybrid delivery system (Thi@ZIF-8). The results demonstrated that Thi@ZIF-8 had a rhombic dodecahedral morphology and a loading capacity of approximately 25%. Notably, the amount of Thi released from Thi@ZIF-8 at a pH of 5.0 reached 79.54%, which was higher than that at pH 7.0 and 9.0, for 251 h. Such pH-responsive release characteristics of Thi@ZIF-8 were probably related to the pH-dependent structure stability of ZIF-8. The release mechanism of Thi@ZIF-8 conformed to non-Fickian diffusion. Additionally, Thi@ZIF-8 showed a higher control efficacy against B. cinerea compared with Thi alone. Importantly, the ZIF-8 carrier could effectively reduce the leaching loss of Thi in soil and showed no negative effects on the three varieties of tomato seedlings, implying good biocompatibility. This work provides a novel and eco-friendly approach to control B. cinerea effectively that has great potential in modern sustainable agriculture.

Modulating Fibrotic Mechanical Microenvironment for Idiopathic Pulmonary Fibrosis Therapy.

Idiopathic pulmonary fibrosis (IPF) is exacerbated by injurious mechanical forces that destabilize the pulmonary mechanical microenvironment homeostasis, leading to alveolar dysfunction and exacerbating disease severity. However, given the inherent mechanosensitivity of fibrotic lungs, where type II alveolar epithelial cells (AEC IIs) are subjected to persistent stretching and overactivated myofibroblasts experience malignant interactions during mechanotransduction, it becomes imperative to develop effective strategies to modulate the pulmonary mechanical microenvironment. Herein, cyclo (RGDfC) peptide-decorated zeolitic imidazolate framework-8 nanoparticles (named ZDFPR NPs) are constructed to target and repair the aberrant mechanical force levels in pathological lungs. Specifically, reduces mechanical tension in AEC IIs by pH-responsive ZDFPR NPs that release zinc ions and 7, 8-dihydroxyflavone to promote alveolar repair and differentiation. Meanwhile, malignant interactions between myofibroblast contractility and extracellular matrix stiffness during mechanotransduction are disrupted by the fasudil inhibition ROCK signaling pathway. The results show that ZDFPR NPs successfully restored pulmonary mechanical homeostasis and terminated the fibrosis process in bleomycin-induced fibrotic mice. This study not only presents a promising strategy for modulating pulmonary mechanical microenvironment but also pioneers a novel avenue for IPF treatment.

FeN4S1 Single-Atom Sites Anchored on Three-Dimensional Porous Carbon for Highly Efficient and Durable Oxygen Electrocatalysis.

Precisely designing asymmetric active centers and exploring their electronic regulation effects to prepare efficient bifunctional single-atom catalysts (SACs) is important for boosting the practical applications of zinc-air batteries (ZABs). Herein, an effective strategy has been developed by introducing an axial S atom to the FeN4 active center, simultaneously assisted by pyrolyzing the graphene oxide (GO) sheathed zeolitic-imidazolate framework-8 (ZIF8) composite and constructing a three-dimensional (3D) porous framework with abundant FeN4S1 moieties. This structure can accelerate the oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) kinetics owing to the modulated electronic redistribution and d-band center with a reduced energy barrier. The optimal S-Fe-NC/rGO showcases a lower voltage gap (ΔE) of 0.64 V between both the ORR and OER half-wave potentials at 10 mA cm-2, highlighting the excellent bifunctional activities. The assembled S-Fe-NC/rGO rechargeable liquid ZABs deliver a power density of 154.05 mW·cm-2 and a desirable durability of >900 h. More importantly, the corresponding flexible solid-state ZABs exhibit considerable foldability.

Injectable Photocrosslinked Hydrogel Dressing Encapsulating Quercetin-Loaded Zeolitic Imidazolate Framework-8 for Skin Wound Healing

Background: Wound management is a critical component of clinical practice. Promoting timely healing of wounds is essential for patient recovery. Traditional treatments have limited efficacy due to prolonged healing times, excessive inflammatory responses, and susceptibility to infection. Methods: In this research, we created an injectable hydrogel wound dressing formulated from gelatin methacryloyl (GelMA) that encapsulates quercetin-loaded zeolitic imidazolate framework-8 (Qu@ZIF-8) nanoparticles. Next, its ability to promote skin wound healing was validated through in vitro experiments and animal studies. Results: Research conducted both in vitro and in vivo indicated that this hydrogel dressing effectively mitigates inflammation, inhibits bacterial growth, and promotes angiogenesis and collagen synthesis, thus facilitating a safe and efficient healing process for wounds. Conclusions: This cutting-edge scaffold system provides a novel strategy for wound repair and demonstrates significant potential for clinical applications.

Twinned Metal-Organic Framework Nanoplates for Hydrocarbon Separation Membranes.

Filler morphology control is critical for enhancing the gas separation performance of mixed matrix membranes (MMMs). A vertical transport channel using the crystal twinning phenomenon is designed on the zeolitic imidazolate framework (ZIF) nanoplate. Twinned ZIF-8 (TZIF-8) nanoplate is prepared by controlling the shape of ZIF-L from nanosheet to twinned flake, followed by conversion into the ZIF-8 phase. With the addition of TZIF-8 in 6FDA-DAM polymer, propylene/propane selectivity is dramatically enhanced, showing propylene permeability of 40 Barrer and propylene/propane selectivity of 82. The separation performance surpasses the performance of MMMs reported so far, and the selectivity is comparable to that of polycrystalline ZIF-8 membranes. A transport mechanism study using mathematical models implies that the percolated twin fillers create rapid and selective gas channels for desired molecules and substantial tortuous pathways for undesired molecules.

Engineering pH and Temperature-Triggered Drug Release with Metal-Organic Frameworks and Fatty Acids

This study reports the successful synthesis of core-shell microparticles utilizing coaxial electrospray techniques, with zeolitic imidazolate framework-8 (ZIF-8) encapsulating rhodamine B (RhB) in the core and a phase change material (PCM) shell composed of a eutectic mixture of lauric acid (LA) and stearic acid (SA). ZIF-8 is well-recognized for its pH-responsive degradation and biocompatibility, making it an ideal candidate for targeted drug delivery. The LA-SA PCM mixture, with a melting point near physiological temperature (39 °C), enables temperature-triggered drug release, enhancing therapeutic precision. The structural properties of the microparticles were extensively characterized through scanning electron microscopy (SEM), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), and thermogravimetric analysis (TGA). Drug release studies revealed a dual-stimuli response, where the release of RhB was significantly influenced by both temperature and pH. Under mildly acidic conditions (pH 4.0) at 40 °C, a rapid and complete release of RhB was observed within 120 h, while at 37 °C, the release rate was notably slower. Specifically, the release at 40 °C was 79% higher than at 37 °C, confirming the temperature sensitivity of the system. Moreover, at physiological pH (7.4), minimal drug release occurred, demonstrating the system’s potential for minimizing premature drug release under neutral conditions. This dual-stimuli approach holds promise for improving therapeutic outcomes in cancer treatment by enabling precise control over drug release in response to both pH and localized hyperthermia, reducing off-target effects and improving patient compliance.

The Throttle Effect in Metal-Organic Frameworks for Distinguishing Water Isotopes.

Metal-organic frameworks (MOFs) have been widely used for separation, but amplifying subtle differences between similar molecules to achieve effective separation remains a great challenge. In this study, we utilize the fluorescent molecule uranine (Ura) to modulate the pores of zeolitic-imidazolate framework 8 (ZIF8), creating an unusual throttle effect. By monitoring fluorescence intensity changes in Ura, the transport diffusion process could be quantified to reveal the diffusion constant of solvents. When we pushed the Ura occupancy to its limit (from 59% to 76% and 98%), the diffusion rate decreases by 2 orders of magnitude. Most importantly, there is a significant dissymmetry between the two-way exchange rates of solvents, and the rates of H2O and D2O became distinguishable. Such unusual throttle effects disappear at low Ura occupancy of 59% and 76%. We believe that the throttle effect with small-molecule loading could provide a universal design principle for MOF-based applications, especially for isotope separation.

Layer-by-Layer Ligands Engineered Gold Nanoclusters on Zeolitic Imidazolate Framework-8 for Efficient Sensing of Lead Ions

Layer-by-Layer Ligands Engineered Gold Nanoclusters on Zeolitic Imidazolate Framework-8 for Efficient Sensing of Lead Ions

Stem Cell Membrane-Camouflaged Biomimetic Nanoparticles Inhibiting Leptin Pathway for Intervertebral Disc Degeneration Therapy.

Leptin, a kind of adipokine, with its receptor in which the long isoform plays a crucial role in signal transduction, has been identified in intervertebral disc (IVD) tissues, especially showing an increased expression in degenerated discs. Initially identified as a metabolic sensor, leptin has recently been found able to regulate inflammation into imbalance, which favors catabolic degradative processes, thus contributing to progressive intervertebral disc degeneration (IDD). Therefore, efficiently inhibiting the leptin pathway may provide a new strategy to treat IDD. In this study, we introduced an innovative drug delivery system (DDS) that employs stem cell membranes (SCM) to encapsulate (Zeolitic imidazolate frameworks-8) ZIF-8 nanoparticles. These nanoparticles are used to transport a plasmid containing shRNA targeting the leptin receptor (LEPR), with the aim of facilitating repair in IDD. The regenerative performances of this DDS in IDD were verified through a combination of the in vitro western blot and immunofluorescence with the in vivo radiologic examination and histological staining. The DDS demonstrated excellent cell adhesion properties and gene transfection efficiency in vitro, along with impressive treatment outcomes in vivo. Both in vitro and in vivo studies revealed that the DDS effectively reduced leptin receptor expression and alleviated the inflammatory environment, thereby promoting regeneration in degenerated IVDs. We propose that the DDS represents a promising novel approach for treating IDD and may also be beneficial for other degenerative diseases linked to leptin pathway dysfunction.

Tailoring-Orientated Deposition of Li2S for Extreme Fast-Charging Lithium-Sulfur Batteries.

Precipitation/dissolution of insulating Li2S has long been recognized as the rate-determining step in lithium-sulfur (Li-S) batteries, which dramatically undermines sulfur utilization at elevated charging rates. Herein, we present an orientated Li2S deposition strategy to achieve extreme fast charging (XFC, ≤15 min) through synergistic control of porosity, electronic conductivity, and anchoring sites of electrode substrate. Via magnesiothermic reduction of a zeolitic imidazolate framework, a nitrogen-doped and hierarchical porous carbon with highly graphitic phase was developed. This design effectively reduces interfacial resistance and ensures efficient sequestration of polysulfides during deposition, leading to (110)-preferred growth of Li2S nanocrystalline between (002)-dominated graphitic layers. Our approach directs an alternative Li2S deposition pathway to the commonly reported lateral growth and 3D thickening growth mode, ameliorating the electrode passivation. Therefore, a Li-S cell capable of charging/discharging at 5C (12 min) while maintaining excellent cycling stability (82% capacity retention) for 1000 cycles is demonstrated. Even under high S loading (8.3 mg cm-2) and low electrolyte/sulfur ratio (3.8 mL mg-1), the sulfur cathode still delivers a high areal capacity of >7 mAh cm-2 for 80 cycles.

Synthesis, Characterization, Density Functional Theory Study, Antibacterial Activity and Molecular Docking of Zeolitic Imidazolate Framework‐8

ABSTRACTIn this study, Zeolitic Imidazolate Framework‐8 (ZIF‐8) nanomaterials were synthesized using a co‐precipitation one‐pot method that uses ethanol, methanol, and water as solvents for the precursors (2‐methylimidazole and Zinc nitrate hexahydrate), resulting in yields of 66.77%, 73.14%, and 68.12%, respectively. The as‐synthesized ZIF‐8 nanomaterials were thoroughly characterized by X‐ray diffraction analysis, transmission electron microscopy, ultraviolet–visible spectroscopy, and Fourier‐transform infrared spectroscopy. The X‐ray diffraction analysis showed that the crystallite size of ethanol‐based ZIF‐8 (24.76 ± 1.67 nm) was smaller than those synthesized in water (26.92 ± 1.89 nm) and methanol (31.39 ± 1.03 nm). However, methanol‐based ZIF‐8 exhibited lower crystallinity (85.93%) than water‐based ZIF‐8 (91.48%) and ethanol‐based ZIF‐8 (92.71%). Zeta potential studies revealed that ethanol‐based ZIF‐8 had a larger surface charge (+37 mV) than water‐based ZIF‐8 (+35 mV) or methanol‐based ZIF‐8 (+24 mV). Transmission electron microscopy analysis confirmed particle sizes of 54.35 ± 2.11 nm for ethanol‐based ZIF‐8, 57.91 ± 2.26 nm for water‐based ZIF‐8, and 63.25 ± 4.12 nm for methanol‐based ZIF‐8. Thermogravimetric analysis indicated thermal stability up to 800 °C, with mass losses of 55.98% for ethanol‐ZIF‐8, 50.12% for water‐based ZIF‐8, and 65.36% for methanol‐based ZIF‐8 by 600 °C. In antibacterial studies, water‐based ZIF‐8 exhibited the largest zone of growth inhibition (17.30 ± 0.26 mm) against Escherichia coli compared to ethanol‐based ZIF‐8 (15.57 ± 0.32 mm) and methanol‐based ZIF‐8 (14.70 ± 0.20 mm). Pearson's correlation study revealed that zeta potential, crystallinity, and antibacterial activity are positively related. Furthermore, water‐based ZIF‐8, with a minimum inhibitory concentration of 50 μg/100 μL, confirmed evident cell membrane disruption. Molecular docking experiments revealed ZIF‐8's significant binding affinity for the E. coli protein 5AZC, supporting its robust antibacterial activity.

Pore Structure Modulation in Kirigamic Zeolitic Imidazolate Framework

Paper crafts, such as origami and kirigami, have become an interdisciplinary research theme transportable from art to science, and further to engineering. Kirigami‐inspired architectural design strategies allow the establishment of three‐dimensional (3D) mechanical linkages with unprecedented mechanical properties. Herein, we report a crystalline zeolitic imidazolate framework (ZIF), displaying folding mechanics based on a kirigami tessellation, originated from the double‐corrugation surface (DCS) pattern. Pressure‐ and guest‐induced responses demonstrate the kirigami mechanism of the ZIF, wherein imidazolate linkers act as hinges, controlling pore dimensionality, resembling the check valve‐adapted mechanical manifold. This discovery of the kirigami tessellation inside a flexible ZIF reveals foldable mechanics at the molecular level.

Pore Structure Modulation in Kirigamic Zeolitic Imidazolate Framework.

Paper crafts, such as origami and kirigami, have become an interdisciplinary research theme transportable from art to science, and further to engineering. Kirigami-inspired architectural design strategies allow the establishment of three-dimensional (3D) mechanical linkages with unprecedented mechanical properties. Herein, we report a crystalline zeolitic imidazolate framework (ZIF), displaying folding mechanics based on a kirigami tessellation, originated from the double-corrugation surface (DCS) pattern. Pressure- and guest-induced responses demonstrate the kirigami mechanism of the ZIF, wherein imidazolate linkers act as hinges, controlling pore dimensionality, resembling the check valve-adapted mechanical manifold. This discovery of the kirigami tessellation inside a flexible ZIF reveals foldable mechanics at the molecular level.

Cascade-catalysed nanocarrier degradation for regulating metabolism homeostasis and enhancing drug penetration on breast cancer

The abnormal structure of tumor vascular seriously hinders the delivery and deep penetration of drug in tumor therapy. Herein, an integrated and tumor microenvironment (TME)-responsive nanocarrier is designed, which can dilate vessle and improve the drug penetration by in situ releasing nitric oxide (NO). Briefly, S-nitroso-glutathione (GSNO) and curcumin (Cur) were encapsulatd into the Cu-doped zeolite imidazole framework-8 (Cu-ZIF-8) and modified with hyaluronic acid. The nanocarrier degradation in the weakly acidic of TME releases Cu2+, then deplete overexpressed intratumourally glutathione and transformed into Cu+, thus disrupting the balance between nicotinamide adenine dinucleotide phosphate and flavin adenine dinucleotide (NADPH/FAD) during the metabolism homeostasis of tumor. The Cu+ can generate highly toxic hydroxyl radical through the Fenton-like reaction, enhancing the chemodynamic therapeutic effect. In addition, Cu+ also decomposes GSNO to release NO by ionic reduction, leading to vasodilation and increased vascular permeability, significantly promoting the deep penetration of Cur in tumor. Afterwards, the orderly operation of cell cycle is disrupted and arrested in the S-phase to induce tumor cell apoptosis. Deep-hypothermia potentiated 2D/3D fluorescence imaging demonstrated nanocarrier regulated endogenous metabolism homeostasis of tumor. The cascade-catalysed multifunctional nanocarrier provides an approach to treat orthotopic tumor.

Ce-doped NiFe-layered-double-hydroxide hierarchical nanocomposite and metal/imidazolate framework carbon nanotube nanocomposite: A bifunctional material for OER electrocatalyst and supercapacitor electrode applications

The development of nanocomposites as electrocatalysts with low cost and high efficiency for OER and as electrode material enhancing the electrochemical performance of supercapacitors are the most popular investigations in this field. Herein, a new bifunctional composite including Ce-doped NiFe-LDH Nanosheets and ZIF-derived carbon base incorporating neodymium and Fe into the structure of Zeolitic Imidazolate Framework is proposed and the construction was through entering Fe-ZIF8@Nd-ZIF67 into the structure of NiFeCe-LDH in different ratios of 10, 20 and 30 %. Various physical and electrochemical tests were conducted to evaluate the nanocomposites. Results indicated that the composite presented a hierarchical porous structure and exhibited outstanding performance for OER and supercapacitor applications. According to the results, the 30 % composite of NiFeCe-LDH/ Fe-ZIF8@Nd-ZIF67 exhibits a superior onset overpotential of 170 mV and an overpotential of 300 mV at a current density of 10 mA·cm−2. Besides, it shows an excellent specific capacitance of 345.36 (F.g−1) at 1 A.g−1. Hence, the synthesized nanocomposite demonstrated outstanding performance in both OER and supercapacitor applications.

Research Progress in Enhancing Proton Conductivity of Sulfonated Aromatic Polymers with ZIFs for Fuel Cell Applications

The escalating global temperatures and their adverse effects underscore the growing imperative for the widespread adoption of clean fuels, notably hydrogen. Proton Exchange Membrane Fuel Cells (PEMFC) emerge as a pivotal green energy technology, facilitating electricity and water generation. The optimization of PEMFC efficiency hinges on the judicious selection and fabrication of polymer membranes. Within innovative materials, Zeolitic Imidazolate Frameworks (ZIFs) represent a novel subclass within the expansive family of Metal-Organic Frameworks (MOFs). ZIFs exhibit promising potential in PEMFCs, owing to their distinctive properties such as a substantial contact surface, inherent porosity, and a sizable pore volume. This comprehensive review delves into composite membranes featuring ZIFs, shedding light on their chemical and thermal attributes. Additionally, the exploration extends to elucidating the diverse applications of ZIF compounds, accompanied by an in-depth discussion of selected chemical and thermal properties inherent to ZIF compounds. Incorporating ZIFs into various polymers yielded intriguing outcomes, demonstrating a notable enhancement in proton conductivity. The compilation of this review aims to provide researchers with foundational insights into the realm of ZIFs, serving as a valuable resource for future investigations and advancements in the field.

Impact of Ligand Concentration on the Properties of Nucleic-Acid-Encapsulated MOFs and Inflammation Modulation in Prostate Cancer Cells.

The zeolitic imidazolate framework (ZIF) is one of the most explored metal-organic-framework-based systems for nucleic acid delivery to cancer cells. Current nucleic acid delivery tools exhibit several drawbacks, such as high manufacturing costs, endosomal entrapment, toxicity, and immunogenicity. However, the biomimetic mineralization of Zn-based ZIFs offers a low-cost and facile encapsulation of nucleic acids at room temperature in aqueous conditions. The efficiency of nucleic acid delivery and its subsequent impact on inflammation in cells are influenced by the physicochemical properties of the material. The imidazole content determines the formation and crystallinity of ZIF, and an optimal ratio ensures the formation of well-defined and highly crystalline structures. In this study, a series of siRNA-encapsulated ZIFs (siRNA@ZIF) were systematically prepared by varying ligand-to-metal (L/M) molar ratios. Our study demonstrates that variations in ligand concentrations influence the crystalline structures, particle size, and shape of siRNA@ZIF particles. At low L/M, two-dimensional siRNA@ZIF particles form with a size of 1 μm. As the L/M ratio increases gradually, the particle size decreases, resulting in three-dimensional particles ∼200 nm in size. We also observed better stability of siRNA@ZIF in water prepared using high L/M values and time-dependent cellular uptake by the cells. Additionally, no significant impact of the biocomposites on inflammation was found, indicating the lack of an unwanted immune response and nonimmunotoxic nature over longer periods (96 h). These findings highlight the necessity of fine-tuning ligand concentrations and synthesis chemistry in designing efficient and optimal ZIF-based systems as versatile delivery platforms for nucleic acids.