Nanoscale Metal-organic Frameworks Research Articles

Light‐Responsive Nanoantennas Integrated into Nanoscale Metal–Organic Frameworks for Photothermal Drug Delivery

Nanoscale metal–organic frameworks (NMOFs) exhibit unique properties for drug delivery, including ultrahigh storage capabilities, biocompatibility, biodegradability, and sustained release of encapsulated cargo. However, due to their localized electronic states, MOFs are nonresponsive to external stimuli such as light or magnetic fields. This study investigates the integration of light‐responsive nanoantennas into NMOFs to enhance their application as smart drug delivery nanosystems. By integrating gold bipyramid nanoantennas within ZIF‐8 and NU‐1000 NMOFs, core@shell nanosystems are created with photothermal capabilities. Utilizing cresyl violet as a model drug, the loading and release dynamics of these nanosystems are analyzed, demonstrating controlled drug release under near‐infrared (NIR) light stimulation. Photothermal release studies conducted in living cells reveal the potential of these nanocomposites for spatiotemporal targeted, light‐activated drug delivery. Further evaluation of the NU‐1000 nanocomposite loaded with chemotherapeutics—doxorubicin, carboplatin, and oxaliplatin—in both 2D and 3D cell cultures shows the nanosystem effectiveness in cell internalization and therapeutic NIR activation. The findings demonstrate that the incorporation of stimuli‐responsive elements into NMOFs offers a promising approach for developing advanced drug delivery platforms.

STING agonist-conjugated metal-organic framework induces artificial leukocytoid structures and immune hotspots for systemic antitumor responses

Abstract Radiotherapy is widely used for cancer treatment, but its clinical utility is limited by radioresistance and its inability to target metastases. Nanoscale metal-organic frameworks (MOFs) have shown promise as high-Z nanoradiosensitizers to enhance radiotherapy and induce immunostimulatory regulation of the tumor microenvironment. We hypothesized that MOFs could deliver small-molecule therapeutics to synergize with radiotherapy for enhanced antitumor efficacy. Herein, we developed a robust nanoradiosensitizer, GA-MOF, by conjugating a STING agonist, 2',3'-cyclic guanosine monophosphate–adenosine monophosphate (GA), on MOF for synergistic radiosensitization and STING activation. GA-MOF demonstrated strong anticancer efficacy by forming immune cell-rich nodules (artificial leukocytoid structures) and transforming them into immunostimulatory hotspots with radiotherapy. Further combination with immune checkpoint blockade suppressed distant tumors through systemic immune activation. Our work not only demonstrates potent radiosensitization of GA-MOF, but also provides the detailed mechanisms regarding MOF distribution, immune regulatory pathways, and long-term immune effects.

Two-photon NIR-responsive carbon dots incorporated into NMOFs for targeted photodynamic therapy

In recent years, Photodynamic therapy (PDT) has shown great potential in clinics to treat cancer. Due to the limited depth range of UV or visible laser light penetration, the eradication of solid tumors using traditional photosensitizer is difficult. Here, we report the development of a new NIR active photosensitizer covalently conjugated to nanoscale metal-organic frameworks (NMOFs) for the eradication of deep-seated tumors. This photosensitizer can generate reactive oxygen species (ROS) in the presence of near-infrared light irradiation (980 nm) for PDT. Therefore, we use a strategy to develop two-photon absorbing carbon dots with a fluorescence quantum yield of 13%. The NMOFs are fabricated in the presence of folic acid, which enables them to target cancer cells that overexpress the folate receptor. NMOFs are used as a nanocarrier for CDs and are employed to achieve targeted PDT. This study is the first to observe that carbon dots embedded in NMOF composite could generate singlet oxygen (1O2) under the 980 nm laser light irradiation and also specifically target cancer cells. At a concentration of 100 μg/ml, the nanocomposite demonstrated a 73% rate of cell inhibition. The primary results reported here will show great potential in the future to develop multifunctional carbon dots for targeted two-photon PDT in the presence of higher wavelength light irradiation.

Aptamer-Functionalized Nanoscale Metal–Organic Frameworks for Targeted Photothermal-Chemo Combined Tumor Therapy

Aptamer-Functionalized Nanoscale Metal–Organic Frameworks for Targeted Photothermal-Chemo Combined Tumor Therapy

Application of metal–organic frameworks in stomatology

Metal–organic frameworks (MOFs), a new class of porous organic–organic hybrid materials controlled by self-assembly of metal atoms and organic pillars, are attracting considerable interest because of their specific properties. More recently, the advantages of different types of nanoscale metal–organic frameworks for the use of MOF nanoparticles in stomatology have been reported in the literature. This article covers the treatment of oral cancer, surface modification of implants, antibacterial dressings, and treatment of periodontitis and periodontal regeneration. It presents recent applications, future challenges, and prospects for MOFs in stomatology in four areas. It provides an overview of recent advances in the design and application of MOFs in stomatology from their intrinsic properties to different syntheses and their use as smart drug delivery systems or a combination of these.

Nanoscale Metal-Organic Frameworks and Nanoscale Coordination Polymers: From Synthesis to Cancer Therapy and Biomedical Imaging.

Recently, there has been significant interest in nanoscale metal-organic frameworks (NMOFs) characterized by ordered crystal structures and nanoscale coordination polymers (NCPs) featuring amorphous structures. These structures arise from the coordination interactions between inorganic metal ions or clusters and organic ligands. Their advantages, such as the ability to tailor composition and structure, efficiently encapsulate diverse therapeutic or imaging agents within porous frameworks, inherent biodegradability, and surface functionalization capability, position them as promising carriers in the biomedical fields. This review provides an overview of the synthesis and surface modification strategies employed for NMOFs and NCPs, along with their applications in cancer treatment and biological imaging. Finally, future directions and challenges associated with the utilization of NMOFs and NCPs in cancer treatment and diagnosis are also discussed.

Zirconium-Based Nanoscale Metal–Organic Framework with Metal-Bridged Cationic Linkers for the Selective Removal of Anionic Dyes

Zirconium-Based Nanoscale Metal–Organic Framework with Metal-Bridged Cationic Linkers for the Selective Removal of Anionic Dyes

Effective antibacterial action of a 2D bimetallic Al/Fe-TCPP NMOF loaded with glucose oxidase by a cascade catalytic reaction and depleting glutathione simultaneously

Nanoscale metal–organic frameworks (NMOFs) with peroxidase-mimicking activity emerged as promising antibacterial agents instead of antibiotics.

Luminescent lanthanide-based molecular materials: applications in photodynamic therapy.

Luminescent lanthanide molecular compounds have recently attracted attention as potential photosensitizers (PSs) for photodynamic therapy (PDT) against malignant cancer tumours because of their predictable systemic toxicity, temporospatial specificity, and minimal invasiveness. A photosensitizer exhibits no toxicity by itself, but in the presence of light and oxygen molecules, it can generate reactive oxygen species (ROS) to cause damage to proteins, nucleic acids, lipids, membranes, and organelles, which can induce cell apoptosis. This review focuses on the latest developments in luminescent lanthanide-based molecular materials as photosensitizers and their applications in photodynamic therapy. These molecular materials include lanthanide coordination complexes, nanoscale lanthanide coordination polymers, and lanthanide-based nanoscale metal-organic frameworks. In the end, the future challenges in the development of robust luminescent lanthanide molecular materials-based photosensitisers are outlined and emphasized to inspire the design of a new generation of phototheranostic agents.

Aptamer-functionalized MOFs and AI-driven strategies for early cancer diagnosis and therapeutics.

Metal-Organic Frameworks (MOFs) have exceptional inherent properties that make them highly suitable for diverse applications, such as catalysis, storage, optics, chemo sensing, and biomedical science and technology. Over the past decades, researchers have utilized various techniques, including solvothermal, hydrothermal, mechanochemical, electrochemical, and ultrasonic, to synthesize MOFs with tailored properties. Post-synthetic modification of linkers, nodal components, and crystallite domain size and morphology can functionalize MOFs to improve their aptamer applications. Advancements in AI and machine learning led to the development of nonporous MOFs and nanoscale MOFs for medical purposes. MOFs have exhibited promise in cancer therapy, with the successful accumulation of a photosensitizer in cancer cells representing a significant breakthrough. This perspective is focused on MOFs' use as advanced materials and systems for cancer therapy, exploring the challenging aspects and promising features of MOF-based cancer diagnosis and treatment. The paper concludes by emphasizing the potential of MOFs as a transformative technology for cancer treatment and diagnosis.

Nanocomposites Based on Magnetic Nanoparticles and Metal-Organic Frameworks for Therapy, Diagnosis, and Theragnostics.

In the last two decades, metal-organic frameworks (MOFs) with highly tunable structure and porosity, have emerged as drug nanocarriers in the biomedical field. In particular, nanoscaled MOFs (nanoMOFs) have been widely investigated because of their potential biocompatibility, high drug loadings, and progressive release. To enhance their properties, MOFs have been combined with magnetic nanoparticles (MNPs) to form magnetic nanocomposites (MNP@MOF) with additional functionalities. Due to the magnetic properties of the MNPs, their presence in the nanosystems enables potential combinatorial magnetic targeted therapy and diagnosis. In this Review, we analyze the four main synthetic strategies currently employed for the fabrication of MNP@MOF nanocomposites, namely, mixing, in situ formation of MNPs in presynthesized MOF, in situ formation of MOFs in the presence of MNPs, and layer-by-layer methods. Additionally, we discuss the current progress in bioapplications, focusing on drug delivery systems (DDSs), magnetic resonance imaging (MRI), magnetic hyperthermia (MHT), and theragnostic systems. Overall, we provide a comprehensive overview of the recent advances in the development and bioapplications of MNP@MOF nanocomposites, highlighting their potential for future biomedical applications with a critical analysis of the challenges and limitations of these nanocomposites in terms of their synthesis, characterization, biocompatibility, and applicability.

Metal-Organic Framework Based Nanozyme System for NLRP3 Inflammasome-Mediated Neuroinflammatory Regulation in Parkinson's Disease.

Neuroinflammation is associated with a series of pathological symptoms in Parkinson's disease (PD), including α-synuclein aggregation and dopaminergic neuronal death. The NOD-like receptor protein 3 (NLRP3) inflammasome plays a crucial role in neuroinflammation at the lesion site and is a promising target for PD treatment. In this study, a nanoscale metal-organic framework (Zr-FeP MOF) based nanozyme is fabricated using Fe-5,10,15,20-tetra (4-carboxyphenyl) porphyrin (Fe-TCPP) and Zr6 cluster as ligands. The Zr-FeP MOF is subsequently encapsulated with mannitol (Man)-liposome, resulting in theformation of Zr-FeP MOF@Man liposome (MOF@Man Liposome) nanozyme system. The in vitro studies show that this nanozyme system is effective in relieving the formation of NLRP3 inflammasome and mitochondrial dysfunction. In mouse models of PD, the nanozyme system demonstrates a significant blood-brain barrier-crossing capability attributed to the Man-mediated brain targeting. Additionally, transcriptomic and biochemical studies show that the nanozyme system effectively inhibits the formation and assembly of inflammasome components, mitigating the activation of glial cells and neuroinflammatory response, and ultimately regulating the pathological symptoms of PD effectively.

A "One Arrow Three Eagle" Strategy to Improve CM-272 Primed Bladder Cancer Immunotherapy.

Immunotherapy using an immune-checkpoint blockade has significantly improved its therapeutic effects. CM-272, which is a novel epigenetic inhibitor of G9a, induces immunogenic cell death (ICD) for recovering the sensitivity to anti-PD-1 antibodies; however, the efficacy of CM-272 is greatly limited by promoting the transcription activity of HIF-1α to form a hypoxic environment. Here, a Fe3+ -based nanoscale metal-organic framework (MIL-53) is used to load CM-272 (ultra-high loading rate of 56.4%) for realizing an MIL-53@CM-272 nanoplatform. After entering bladder cancer cells, Fe3+ not only promotes the decomposition of H2 O2 into O2 for O2 -compensated sonodynamic therapy but reduces the high level of glutathione in the tumor microenvironment (TME) for enhancing reactive oxygen species, including ferroptosis and apoptosis. MIL-53 carriers can be degraded in response to the TME, accelerating the release of CM-272, which helps achieve the maximum effectiveness in an O2 -sufficient TME by attenuating drug resistance. Furthermore, MIL-53@CM-272 enhances dendritic cell maturation and synergistically combines it with an anti-programmed cell death protein 1 antibody during the study of immune-related pathways in the transcriptomes of bladder cancer cells using RNA-seq. This study presents the first instance of amalgamating nanomedicine with CM-272, inducing apoptosis, ferroptosis, and ICD to achieve the "one arrow three eagle" effect.

Spatial targeting of fibrosis-promoting macrophages with nanoscale metal-organic frameworks for idiopathic pulmonary fibrosis therapy

Targeted delivery of therapeutic drugs to fibrosis-promoting macrophages (FPMs) holds promise as a challenging yet effective approach for the treatment of idiopathic pulmonary fibrosis (IPF). Here, nanocarriers composed of Mn-curcumin metal-organic frameworks (MOFs) were utilized to deliver the immune inhibitor BLZ-945 to the lungs, with the goal of depleting fibrosis-promoting macrophages (FPMs) from fibrotic lung tissues. FPM targeting was achieved by functionalizing the nanocarrier surface with an M2-like FPM binding peptide (M2pep). As a result, significant therapeutic benefits were observed through the successful depletion of approximately 80 % of the M2-like macrophages (FPMs) in a bleomycin-induced fibrosis mouse model treated with the designed M2-like FPM-targeting nanoparticle (referred to as M2NP-BLZ@Mn-Cur).Importantly, the released Mn2+ and curcumin after the degradation of M2NP-BLZ@Mn-Cur accumulated in the fibrotic lung tissue, which can alleviate inflammation and oxidative stress reactions, thereby further improving IPF therapy. This study presents a novel strategy with promising prospects for molecular-targeted fibrosis therapy. Statement of significanceMetal−organic frameworks (MOFs)- based nanocarriers equipped with both fibrosis-promoting macrophage (FPM)-specific targeting ability and therapeutic drugs are appealing for pulmonary fibrosis treatment. Here, we prepared M2pep (an M2-like FPM binding peptide)-modified and BLZ945 (a small molecule inhibitor of CSF1/CSF-1R axis)-loaded Mn-curcumin MOF nanoparticles (M2NP-BLZ@Mn-Cur) for pulmonary fibrosis therapy. The functionalized M2NP-BLZ@Mn-Cur nanoparticles can be preferentially taken up by FPMs, resulting in their depletion from fibrotic lung tissues. In addition, Mn2+and curcumin released from the nanocarriers have anti-inflammation and immune regulation effects, which further enhance the antifibrotic effect of the nanoparticles.

An Ellagic Acid Coordinated Copper-Based Nanoplatform for Efficiently Overcoming Cancer Chemoresistance by Cuproptosis and Synergistic Inhibition of Cancer Cell Stemness.

Drug resistance is one of the leading causes of treatment failure in current cancer chemotherapy. In addition to the classical drug efflux transporter-mediated chemoresistance, cancer cells with stemness features play a crucial role in escaping the maximum impact of chemotherapy. To sensitize cancer chemotherapy, in a novel approach, the hedgehog pathway inhibitor ellagic acid (EA) is coordinated with Cu2+ to develop nanoscale metal-organic frameworks (EA-Cu), which are then loaded with doxorubicin (DOX) and modified with targeted chondroitin sulfate (CS) to form the CS/E-C@DOX nanoplatform (CS/NPs). Notably, EA inhibits stemness maintenance by suppressing the hedgehog pathway, while Cu2+ further decreases stemness features of tumor cells by disrupting mitochondrial metabolism, effectively enhancing DOX-mediated chemotherapy. Meanwhile, EA can act synergistically with Cu2+ to cause mitochondrial dysfunction and cuproptosis, which effectively decreases ATP levels and subsequently suppresses the activity of P-glycoprotein (P-gp), thus reducing drug efflux and sensitizing DOX-mediated chemotherapy. Additionally, the attached CS endows CS/NPs with specific tumor targeting properties, whereas EA-Cu endows this nanoplatform with pH/glutathione (GSH) dual-responsive release behavior. Taken together, CS/NPs exhibited excellent antitumor effects by inducing cuproptosis and significantly inhibiting cancer cell stemness, which has great potential for overcoming cancer chemoresistance.

Dissipative enzymatic catalysis-driven modulation of coordination mode and cation valence in MOFs responsive for dual-modality enzyme assay

A dual-modality enzyme assay combining the fluorescence and colorimetry merits based on nanoscale metal-organic frameworks (nMOFs) was established for the analysis of glutathione S-transferase (GST). In this design, HKUST-1 with CuII metal nodes, was chosen as nMOFs and encapsulated with rhodamine 6 G (Rho 6 G) in one-step reaction to fabricate the functional nMOFs (Rho 6 G@Cu-MOFs). As a proof of concept, as a GST binding substrate, reductive glutathione (GSH) invokes competitive coordination with Cu nodes through sulfur atom as well as the valence transformation, of which the process results in coordination bond leakage and even framework collapse, leading to the releasing of internal Rho 6 G dyes for fluorescence-modality analysis. In addition, reductive GSH can interact with Cu nodes in the nMOFs and modulate CuII to CuI, along with a color change for colorimetry analysis. The dual-modality assay shows high analytical performance for GST quantification in a linear range of 0.25–100 nM with a detection limit down to 0.13 nM for fluorescence modality, and a linear range of 1–100 nM with a detection limit of 0.64 nM for colorimetry modality. In addition, the precision of the dual-modality assay shows good agreements with commercial GST activity assay kit.

Facile preparation of metal-organic framework beads for effective capture of indium ion

The adsorption and recovery of indium (In) ions from water is necessary while still faces challenges. Current adsorbents for this valuable metal commonly show powder states, which easily results in mass loss and goes against their convenient recovery. In this work, the nanoscale metal-organic framework UiO-66-(COOH)2 particles were successfully embedded in sodium alginate (SA)-calcium structure, to fabricate UiO-66-(COOH)2/SA composite beads. The beads show a homogenous size of ∼3 mm, cellular-like interior structure, and high MOF loading amount (70.4 wt%). Besides, their high water stability and anti-pressure property were proved. UiO-66-(COOH)2/SA beads exhibit a large adsorption amount for In3+ ions (81.2 mg g−1) and rapid adsorption equilibrium time (∼5 min) at low concentrations. Importantly, it is found that In3+ ions can diffuse into the interior frameworks of the beads via the transparent transmission channels. The optimal pH for adsorption locates at 4.0 and temperature may have only a slight effect. Furthermore, the beads can be regenerated based on a simple solvent elution method. The mechanism analysis confirms that the C–O–C and C–OH (or –COOH) groups from both SA and MOF contents contribute to the adsorption. So, our work provides an effective bead-state adsorbent for In3+ ions.

Self‐Aggregated Nanoscale Metal–Organic Framework for Targeted Pulmonary Decorporation of Uranium (Adv. Healthcare Mater. 25/2023)

Self‐Aggregated Nanoscale Metal–Organic Framework for Targeted Pulmonary Decorporation of Uranium (Adv. Healthcare Mater. 25/2023)

Nanoscale Metal-Organic Frameworks Combined with Metal Nanoparticles and Metal Oxide/Peroxide to Relieve Tumor Hypoxia for Enhanced Photodynamic Therapy.

Photodynamic therapy (PDT) is a clinically approved noninvasive tumor therapy that can selectively kill malignant tumor cells, with promising use in the treatment of various cancers. PDT is typically composed of three important parts: the specific wavelength of light, photosensitizer (PS), and oxygen. With the progressing investigation on PDT treatment, the most recent attention has focused on improving photodynamic efficiency. Tumor hypoxia has always been a critical factor hindering the efficacy of PDT. Nanoscale metal-organic frameworks (nMOF), the fourth generation of PS, present great potential in photodynamic therapy. In particular, nMOF combined with metal nanoparticles and metal oxide/peroxide has demonstrated unique properties for enhanced PDT. The metal and metal oxide nanoparticles can catalyze H2O2 to generate oxygen or automatically produces oxygen, alleviating the hypoxia and improving the photodynamic efficiency. Metal peroxide nanoparticles can spontaneously produce oxygen in water or under acidic conditions. Therefore, this Review summarizes the recent development of nMOF combined with metal nanoparticles (platinum nanoparticles and gold nanoparticles) and metal oxide/peroxide (manganese dioxide, ferric oxide, cerium oxide, calcium peroxide, and magnesium peroxide) for enhanced photodynamic therapy by alleviating tumor hypoxia. Finally, future perspectives of nMOF combined nanomaterials in PDT are put forward.

PEGylated chitosan decorated UiO-66 nanoscale metal–organic frameworks as promising carriers for drug delivery

PEGylated chitosan decorated UiO-66 nanoscale metal–organic frameworks as promising carriers for drug delivery