Effect of sub-acute exposure of metal-organic framework-199 on cognitive function and oxidative stress level of brain tissue in rat.

Metal-Organic Framework-199 (MOF-199) is a subgroup of MOFs that is utilized in different medical fields such as drug delivery. In the current study, the effect of sub-acute exposure to MOF-199 on spatial memory, working memory, inflammatory mediators' expression, and oxidative stress level of brain tissue has been investigated. Thirty-two male Wistar rats were randomly divided into four groups as vehicle, MOF-199 at doses 0.3, 3, or 6 mg/kg. After four injections of relevant interventions via tail vein during 14 days, behavioral parameters were investigated using Y-maze and Morris Water Maze (MWM) tests. Oxidative stress was measured by ferric reducing antioxidant power (FRAP) and thiobarbituric acid-reacting substance (TBARS) tests. The expression levels of TNF-α and IL-1ß were assessed by quantitative real-time reverse-transcription PCR (qRT-PCR). No significant differences were observed in working memory, spatial learning and memory of MOF-199 receiving rats. Additionally, the level of oxidative stress and inflammatory genes expression were not remarkably changed in the brain tissues of MOF-199 treated rats. Despite the lack of remarkable toxic effects of sub-acute exposure to MOF-199, more studies with a longer duration of administration are necessary to use this substance for drug delivery systems in diseases related to the nervous system.

In-silico green toxicology approach toward discovering safer ligands for development of safe-by-design metal-organic frameworks.

A vast variety of chemical compounds have been fabricated and commercialized, they not only result in industrial exposure during manufacturing and usage, but also have environmental impacts throughout their whole life cycle. Consequently, attempts to assess the risk of chemicals in terms of toxicology have never ceased. In-silico toxicology, also known as predictive toxicology, has advanced significantly over the last decade as a result of the drawbacks of experimental investigations. In this study, ProTox-III was applied to predict the toxicity of the ligands used for metal-organic framework (MOF) design and synthesis. Initially, 35 ligands, that have been frequently utilized for MOF synthesis and fabrication, were selected. Subsequently, canonical simplified molecular-input line-entry system (SMILES) of ligands were extracted from the PUBCHEM database and inserted into the ProTox-III online server. Ultimately, webserver outputs including LD50 and the probability of toxicological endpoints (cytotoxicity, carcinogenicity, mutagenicity, immunotoxicity, and ecotoxicity) were obtained and organized. According to retrieved LD50 data, the safest ligand was 5-hydroxyisophthalic. In contrast, the most hazardous ligand was 5-chlorobenzimidazole, with an LD50 of 8 mg/kg. Among evaluated endpoints, ecotoxicity was the most active and was detected in several imidazolate ligands. This data can open new horizons in design and development of green MOFs.

In situ investigation of detoxification and metabolic effects of polyfluoroalkyl substances on metal-organic frameworks combined with cell-cultured microfluidics.

Over 9000 types of per- and polyfluoroalkyl substances (PFASs) have been produced that exhibit environmental persistence, bioaccumulation and biotoxicity, and pose a potential hazard to human health. Although metal-organic frameworks (MOFs) are promising structure-based materials for adsorbing PFASs, the enormous structural diversity and variability of the pharmacologic action of PFASs present challenges to the development of structure-based adsorbents. To address this issue, we propose an in situ platform for the high-throughput identification of efficient MOF sorbents that can adsorb PFASs and their metabolism using a filter-chip-solid phase extraction-mass spectrometry (SPE-MS) system. As a proof of concept, we screened BUT-16 as an attractive material for in situ fluorotelomer alcohol (FTOH) adsorption. The results demonstrated that FTOH molecules were adsorbed around the surface of the large hexagonal pores of BUT-16 by forming multiple hydrogen bonding interactions with its Zr6 clusters. The FTOH removal efficiency of the BUT16 filter was 100% over a period of 1 min. To determine the FTOH metabolism effects in different organs, HepG2 human hepatoma, HCT116 colon cancer, renal tubular HKC, and vascular endothelial HUVEC cells were cultured on a microfluidic chip, and SPE-MS was used to track a variety of cell metabolites in real time. Overall, the filter-Chip-SPE-MS system is a versatile and robust platform for the real-time monitoring of noxious pollutant detoxification, biotransformation, and metabolism, which facilitates pollutant antidote development and toxicology assay.

Size- and shape-dependent cytotoxicity of nano-sized Zr-based porphyrinic metal-organic frameworks to macrophages.

The wide utilization of nano-sized metal-organic frameworks (NMOFs) leads to inevitable health risks to humans. Previous studies on health risks of NMOFs mainly focus on the cytotoxic tests of typical NMOFs，but lack sufficient studies on the effects of physiochemical characteristics of NMOFs on the cytotoxicity and the related mechanisms. Here, four kinds of Zr-based porphyrinic NMOFs (PCNs), including spherical 30, 90, and 180 nm PCN-224 and rod-like 90 nm PCN-222, were taken as a proof of the concept to investigate the effects of the size and shape of NMOFs on the cytotoxicity and related mechanisms to macrophages. The 30 nm spherical PCN-224 induced significant rupture of cell membrane and dissolved in lysosome, leading to the most significant cell necrosis among the studied other nano-sized PCNs. However, other studied PCNs showed insignificant membrane rupture and their dissolution in lysosome. Furthermore, the 90 nm-sized PCN-224 led to much more significant cell necrosis by inducing lysosome damage and inhibiting of autophagy flux than the rod-like 90 nm PCN-222. These findings reveal the size- and shape-dependent cytotoxicity of PCNs and the related mechanisms and are helpful to the assessment of the potential health risks of NMOFs and the safe application of NMOFs.

Light-Activated Biodegradable Covalent Organic Framework-Integrated Heterojunction for Photodynamic, Photothermal, and Gaseous Therapy of Chronic Wound Infection.

Chronic wound healing, impeded by bacterial infections and drug resistance, poses a threat to global human health. Antibacterial phototherapy is an effective way to fight microbial infection without causing drug resistance. Covalent organic frameworks (COFs) are a class of highly crystalline functional porous carbon-based materials composed of light atoms (e.g., carbon, nitrogen, oxygen, and borane), showing potential applications in the biomedical field. Herein, we constructed porphyrin-based COF nanosheets (TP-Por CON) for synergizing photodynamic and photothermal therapy under red light irradiation (e.g., 635 nm). Moreover, a nitric oxide (NO) donor molecule, BNN6, was encapsulated into the pore volume of the crystalline porous framework structure to moderately release NO triggered by red light irradiation for realizing gaseous therapy. Therefore, we successfully synthesized a novel TP-Por CON@BNN6-integrated heterojunction for thoroughly killing Gram-negative bacteria Escherichia coli and Gram-positive bacteria Staphylococcus aureus in vitro. Our research identified that TP-Por CON@BNN6 has favorable biocompatibility and biodegradability, low phototoxicity, anti-inflammatory properties, and excellent mice wound healing ability in vivo. This study indicates that the TP-Por CON@BNN6-integrated heterojunction with multifunctional properties provides a potential strategy for COF-based gaseous therapy and microorganism-infected chronic wound healing.

Metal-Organic Framework-Based Nanoagents for Effective Tumor Therapy by Dual Dynamics-Amplified Oxidative Stress.

Overproduction of reactive oxygen species (ROS) within tumors can cause oxidative stress on tumor cells to induce death, which has motivated us to develop ROS-mediated tumor therapies, such as typical photodynamic therapy (PDT) and Fenton reaction-mediated chemodynamic therapy (CDT). However, these therapeutic modalities suffer from compromised treatment efficacy owing to their limited generation of highly reactive ROS in a tumor microenvironment (TME). In this work, a nanoscale iron-based metal-organic framework, MIL-101(Fe), is synthesized as a Fenton nanocatalyst to perform the catalytic conversion of hydroxyl radicals (·OH) from hydrogen peroxide (H2O2) under the acidic environment and as a biocompatible and biodegradable nanocarrier to deliver a 5,10,15,20-tetrakis(4-carboxyphenyl)porphyrin (TCPP) photosensitizer for light-activated singlet oxygen (1O2) generation. By coupling such chemodynamic/photodynamic effects, the photosensitizer-integrated nanoagents (MIL-101(Fe)@TCPP) could enable more ROS production within tumors to induce amplified oxidative damage for tumor-specific synergistic therapy. In vitro results show that MIL-101(Fe)@TCPP nanoagents achieve the acid-responsive CDT and effective PDT, and synergistic CDT/PDT provides an enhanced therapeutic effect. Ultimately, based on such synergistic therapy, MIL-101(Fe)@TCPP nanoagents cause a significant tumor growth inhibition in vivo without severe side effects, showing great potential for anti-tumor application.

Black Phosphorus Nanosheet Encapsulated by Zeolitic Imidazole Framework-8 for Tumor Multimodal Treatments.

Black phosphorus (BP) nanosheet is easily oxidized by oxygen and water under ambient environment, thus, reliable BP passivation techniques for biomedical applications is urgently needed. A simple and applicable passivation strategy for biomedical applications was established by encapsulating BP nanosheet into zeolitic imidazole framework-8 (ZIF-8). The resulted BP nanosheet in ZIF-8 (BP@ZIF-8) shows not only satisfied chemical stability in both water and phosphate buffered saline (PBS), but also excellent biocompatibility. Notably, BP nanosheet endows the prepared BP@ZIF-8 with prominent photothermal conversion efficiency (31.90%). Besides passivation BP, ZIF-8 provides the BP@ZIF-8 with high drug loading amount (1353.3 mg g-1). Moreover, the loaded drug can be controlled release by pH stimuli. Both in vitro and in vivo researches verified the resulted BP@ZIF-8 an ideal candidate for tumor multimodal treatments.

Covalent Organic Framework-Derived Carbonous Nanoprobes for Cancer Cell Imaging.

Covalent organic frameworks (COFs) have emerged as promising materials for biomedical applications, but their functions remain to be explored and the potential toxicity concerns should be resolved. Herein, it is presented that carbonization significantly enhances the fluorescence quenching efficiency and aqueous stability of nanoscale COFs. The probes prepared by physisorbing dye-labeled nucleic acid recognition sequences onto the carbonized COF nanoparticles (termed C-COF) were employed for cell imaging, which could effectively light up biomarkers (survivin and TK1 mRNA) in living cells. The C-COF has enhanced photothermal conversion capacity, indicating that the probes are also promising candidates for photothermal therapy. The potential toxicity concern from the aromatic rigid building units of COFs was detoured by carbonization. Overall, carbonization is a promising strategy for developing biocompatible and multifunctional COF-derived nanoprobes for biomedical applications. This work may inspire more versatile COF-derived nanoprobes for bioanalysis and nanomedicine.

Synthesis of Polyhedral Metal-Organic Framework@Mesoporous Silica Hybrid Nanocomposites with Branched Shapes.

The structural modulation of multicompartment porous nanomaterials is one of the major challenges of nanoscience. Herein, by utilizing the polyhedral effects/characteristics of metal-organic frameworks (MOFs), we present a versatile approach to construct MOF-organosilica hybrid branched nanocomposites with MOF cores, SiO2 shells, and periodic mesoporous organosilica (PMO) branches. The morphology, structure, and functions of the obtained hybrid nanocomposites can be facilely modulated by varying particle size, shape, or crystalline structures of the MOF cores. Specifically, these branched multicompartment porous nanoparticles exhibit evasion behaviors in epithelial cells compared with macrophage cells, which may endow them great potential as a vehicle for immunotherapy.

Cellular evaluation of the metal-organic framework PCN-224 associated with inflammation and autophagy.

Metal-organic frameworks (MOFs) are innovative porous structures consisting of metal ions and organic ligands, which have been verified for extraordinary applications in nanomedicine and pharmaceuticals. PCN-224 is a type of Zr-based MOFs, which has recently emerged as one of the most attractive nanomaterials for various applications, such as drug delivery, bioimaging and cancer therapy due to its favorable and fascinating physical-chemical properties. However, the safety evaluation and the potential toxicological properties remain unclear. In this study, the general cytotoxicity of PCN-224 were examined in both human hepatocytes L-02 cells and mouse macrophages RAW264.7. Furthermore, the effect of inflammation and autophagy were measured in L-02 cells. The results indicated that PCN-224 was engulfed in L-02 cells and subsequently resulted in morphological changes, cell membrane destruction, and oxidative stress in L-02 cells. PCN-224 might trigger inflammation by promoting the secretion of inflammatory factors such as Tumor necrosis factors (TNF-α) and Interleukin (IL-6). PCN-224 might induce autophagosome accumulation and subsequently autophagic dysfunction. Additionally, PCN-224 induced cytotoxicity in RAW264.7 cells and increased the protein levels of the inflammasome component NLR Family Pyrin Domain Containing 3 (NLRP3) molecular, which indicated its cellular effects in different cell types. All of these results will support the reasonable use of PCN-224.

Core-Shell Nanosystems for Self-Activated Drug-Gene Combinations against Triple-Negative Breast Cancer.

The combination of gene therapy with chemotherapeutics provides an efficacious strategy for enhanced tumor therapy. RNA-cleaving DNAzyme has been recognized as a promising gene-silencing tool, while its combination with chemotherapeutic drugs has been limited by the lack of an effective codelivery system to allow sufficient intracellular DNAzyme activation, which requires specific metal ions as a cofactor. Here, a self-activatable DNAzyme/drug core-shell codelivery system is fabricated to combat triple-negative breast cancer (TNBC). The hydrophobic chemotherapeutic, rapamycin (RAP), is self-assembled into the pure drug nanocore, and the metal-organic framework (MOF) shell based on coordination between Mn2+ and tannic acid (TA) is coated on the surface to coload an autophagy-inhibiting DNAzyme. The nanosystem efficiently delivers the payloads into tumor cells, and upon endocytosis, the MOF shell is disintegrated to release the therapeutics in response to an acidic endo/lysosome environment and intracellular glutathione (GSH). Notably, the coreleased Mn2+ serves as the cofactor of DNAzyme for effective self-activation, which suppresses the expression of Beclin 1 protein, the key initiator of autophagy, resulting in a significantly strengthened antitumor effect of RAP. Using tumor-bearing mouse models, the nanosystem could passively accumulate into the tumor tissue, impose potent gene-silencing efficacy, and thus sensitize chemotherapy to inhibit tumor growth upon intravenous administration, providing opportunities for combined gene-drug TNBC therapy.

MOF-derived novel porous Fe3O4@C nanocomposites as smart nanomedical platforms for combined cancer therapy: magnetic-triggered synergistic hyperthermia and chemotherapy.

Multifunctional nanomedical platforms have broad prospects in imaging-guided combination therapy in cancer precision medicine. In this work, metal-organic framework (MOF)-derived novel porous Fe3O4@C nanocomposites were developed as an intelligent cancer nanomedical platform for combined cancer therapy with MRI-guided magnetic-triggered hyperthermia and chemotherapy functions. The magnetic behavior, porous character and good surface modification endowed this smart nanoplatform with favorable biocompatibility, high-efficiency MRI imaging, magnetic-triggered on-demand DOX release function, and synergistic therapy of magnetic hyperthermia and chemotherapy, which proposed an all-in-one platform for cancer therapy. Additionally, in vivo animal experiments verified the significant suppression of malignant tumor growth with negligible side effects, which were attributed to the consecutive 13 day synergistic therapy of magnetic hyperthermia and chemotherapy in one. To be specific, Fe3O4@C-PVP@DOX significantly decreases the volume (2.5 to 0.44 of tumor volume ratio) and weight (0.49 g to 0.10 g) of tumors after magnetic-triggered hyperthermia and chemotherapy treatments. Moreover, no big difference of body weight and associated damage was observed among all major organs. Therefore, owing to its high-efficiency combined therapy of magnetic-triggered hyperthermia and chemotherapy, this smart nanoplatform holds great potential application in the precise treatments of clinical cancer.

Size- and dose-dependent cytotoxicity of ZIF-8 based on single cell analysis.

ZIF-8 nanoparticles (NPs) has been demonstrated with good potential in drug delivery, which causes an increasing attention on relevant toxicity study. In this work, MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide), glutathione (GSH), reactive oxygen species (ROS), stain analysis and gene detection assays were performed on ZIF-8 (50, 90 and 200 nm) incubated HepG2 cells. Moreover, time-resolved inductively coupled plasma mass spectrometry (TRA-ICP-MS) was applied for single cell analysis; the variation in cellular zinc amount and the proportion of zinc up-taken cells was investigated as a function of NPs size, incubation concentration/time and elimination. Smaller size of ZIF-8 NPs would lead to higher zinc accumulation and toxicity. The function of ZIF-8 on cells is assumed to be mainly related to zinc intracellular accumulation. The possible action path is presented as high accumulation of zinc in ZIF-8 incubated cells lead to high ROS level and cellular inflammation, ultimately inducing necrocytosis. For better understanding of the bio-effect of ZIF-8, ZnO NPs and Zn2+ incubated HepG2 cells were evaluated in the same way. Higher accumulation of zinc in larger part of the cell population was found in ZIF-8 incubated cells than that in ZnO NPs incubated cells. It demonstrated higher bioavailability for ZIF-8 over ZnO NPs. While, in drug delivery application, the possible risk of the remained intracellular ZIF-8 cannot be ignored.

MOF-Derived Double-Layer Hollow Nanoparticles with Oxygen Generation Ability for Multimodal Imaging-Guided Sonodynamic Therapy.

The high reactive oxygen species (ROS) generation ability and simple construction of sonosensitizer systems remain challenging in sonodynamic therapy against the hypoxic tumor. In this work, we rationally prepared MOF-derived double-layer hollow manganese silicate nanoparticle (DHMS) with highly effective ROS yield under ultrasound irradiation for multimodal imaging-guided sonodynamic therapy (SDT). The presence of Mn in DHMS increased ROS generation efficiency because it could be oxidized by holes to improve the electron-hole separation. Moreover, DHMS could produce oxygen in the tumor microenvironment, which helps overcome the hypoxia of the solid tumor and thus enhance the treatment efficiency. In vivo experiments demonstrated efficient tumor inhibition in DHMS-mediated SDT guided by ultrasound and magnetic resonance imaging. This work presents a MOF-derived nanoparticle with sonosensitive and oxygen generating ability, which provides a promising strategy for tumor hypoxia in SDT.

Bioinspired Construction of a Nanozyme-Based H2O2 Homeostasis Disruptor for Intensive Chemodynamic Therapy.

The insufficient intracellular H2O2 level in tumor cells is closely associated with the limited efficacy of chemodynamic therapy (CDT). Despite tremendous efforts, engineering CDT agents with a straightforward and secure H2O2 supplying ability remains a great challenge. Inspired by the balance of H2O2 generation and elimination in cancer cells, herein, a nanozyme-based H2O2 homeostasis disruptor is fabricated to elevate the intracellular H2O2 level through facilitating H2O2 production and restraining H2O2 elimination for enhanced CDT. In the formulation, the disruptor with superoxide dismutase-mimicking activity can convert O2•- to H2O2, promoting the production of H2O2. Simultaneously, the suppression of catalase activity and depletion of glutathione by the disruptor weaken the transformation of H2O2 to H2O. Thus, the well-defined system could perturb the H2O2 balance and give rise to the accumulation of H2O2 in cancer cells. The raised H2O2 level would ultimately amplify the Fenton-like reaction-based CDT efficiency. Our work not only paves a way to engineer alternative CDT agents with a H2O2 supplying ability for intensive CDT but also provides new insights into the construction of bioinspired materials.

Biocompatible, Crystalline, and Amorphous Bismuth-Based Metal-Organic Frameworks for Drug Delivery.

The synthetic flexibility of metal-organic frameworks (MOFs) with high loading capacities and biocompatibility makes them ideal candidates as drug delivery systems (DDSs). Here, we report the use of CAU-7, a biocompatible bismuth-based MOF, for the delivery of two cancer drugs, sodium dichloroacetate (DCA) and α-cyano-4-hydroxycinnamic acid (α-CHC). We achieved loadings of 33 and 9 wt % for DCA and α-CHC, respectively. Interestingly, CAU-7 showed a gradual release of the drugs, achieving a release time of up to 17 days for DCA and 31 days for α-CHC. We then performed mechanical and thermal amorphization processes to attempt to delay the delivery of guest molecules even more. With the thermal treatment, we were able to achieve an outstanding 32% slower release of α-CHC from the thermally treated CAU-7. Using in vitro studies and endocytosis inhibitors, confocal microscopy, and fluorescence-activated cell sorting, we also demonstrated that CAU-7 was successfully internalized by cancer cells, partially avoiding lysosome degradation. Finally, we showed that CAU-7 loaded either with DCA or α-CHC had a higher therapeutic efficiency compared with the free drug approach, making CAU-7 a great option for biomedical application.

Construction of an iridium(iii)-complex-loaded MOF nanoplatform mediated with a dual-responsive polycationic polymer for photodynamic therapy and cell imaging.

A multifunctional photodynamic therapy (PDT) nanoplatform, characterized by red-shifted absorption and emission, was fabricated using an UiO-66-based metal-organic framework (MOF), a biscyclometalated iridium(iii) complex, and a pH/ROS-responsive polycationic polymer. Noticeably, this promising nanoplatform exhibited good biocompatibility in the dark and produced abundant ROS upon light irradiation, which could achieve apparent endo/lysosome escape and kill cancer cells effectively.

Multifunctional drug carrier on the basis of 3d-4f Fe/La-MOFs for drug delivery and dual-mode imaging.

Multifunctional drug carriers for simultaneous imaging and drug delivery have emerged as an important new direction for the treatment of cancer. In this study, 3d-4f heterometallic Fe/La-MOFs, with excellent fluorescence and superior positive magnetic resonance imaging with high resolution, were synthesized successfully. The feasibility of Fe/La-MOFs for use in multifunctional drug delivery was demonstrated using doxorubicin hydrochloride (DOX) as the drug model. After modification with tunable amino modified silica layers, the drug loading increased to 150.2 mg g-1 from 23.9 mg g-1, and the pH responsive drug release climbed 80% from 10% upon regulating the pH from 5.8 to 7.4. T2-Weighted magnetic resonance imaging (MRI) and fluorescence optical imaging (FOI) both showed a clear concentration-dependent contrast enhancement, indicating potential application as a MRI/FOI dual mode imaging agent. In addition, the FOI of 4T1 cells loaded with Fe/La-MOFs demonstrated their capacity for imaging living cells. The particles were tracked by MRI, and the transverse relativity (r2) ranks among the highest reported for Fe3+complexes (100.49 mM-1 s-1). In summary, this is the first report on 3d-4f MOF particles displaying pH-responsive delivery and MRI/FOI dual mode imaging.

Toxicity screening of two prevalent metal organic frameworks for therapeutic use in human lung epithelial cells.

INTRODUCTION: The flexibility and tunability of metal organic frameworks (MOFs), crystalline porous materials composed of a network of metal ions coordinated by organic ligands, confer their variety of applications as drug delivery systems or as sensing and imaging agents. However, such properties also add to the difficulty in ensuring their safe implementation when interaction with biological systems is considered. METHODS: In the current study, we used real-time sensorial strategies and cellular-based approaches to allow for fast and effective screening of two MOFs of prevalent use, namely, MIL-160 representative of a hydrophilic and ZIF-8 representative of a hydrophobic framework. The two MOFs were synthesized "in house" and exposed to human bronchial epithelial (BEAS-2B) cells, a pertinent toxicological screening model. RESULTS: Analysis allowed evaluation and differentiation of particle-induced cellular effects as well identification of different degrees and routes of toxicity, all in a high-throughput manner. Our results show the importance of performing screening toxicity assessments before introducing MOFs to biomedical applications. DISCUSSION: Our proposed screening assays could be extended to a wider variety of cell lines to allow for identification of any deleterious effects of MOFs, with the range of toxic mechanisms to be differentiated based on cell viability, morphology and cell-substrate interactions, respectively. CONCLUSION: Our analysis highlights the importance of considering the physicochemical properties of MOFs when recommending a MOF-based therapeutic option or MOFs implementation in biomedical applications.

A fluorescent nanoprobe based on azoreductase-responsive metal-organic frameworks for imaging VEGF mRNA under hypoxic conditions.

As VEGF mRNA is an endothelial cell-specific mitogen and a key regulator of angiogenesis in a variety of physiological and pathological processes, high expression levels of VEGF messenger RNA (mRNA) contribute to VEGF-driven angiogenesis in the hypoxic areas of solid tumors and then disrupt the vascular barrier, which may potentiate tumor cell extravasation. Thus, monitoring the changes in VEGF mRNA is necessary to understand the genetic programme under hypoxic conditions and thus facilitate risk assessment and risk reduction in hypoxic environments. Herein, a new fluorescent nanoprobe based on azoreductase-responsive functional metal-organic frameworks (AMOFs) was developed to realize the imaging of VEGF mRNA under hypoxic conditions. Since the azobenzene units in the AMOFs can be reduced to amines by the highly expressed azoreductase in an oxygen-deficient environment, the VEGF mRNA-targeted molecular beacon (MB), which is adsorbed on the surface of AMOFs via electrostatic interactions, can be released due to the structural damage of AMOFs. Moreover, TAMRA (carboxytetramethylrhodamine, donor) and Cy5 (acceptor) were close to each other due to the stem-loop conformation of MB, thus inducing high fluorescence energy resonance transfer (FRET) efficiency. Upon the addition of VEGF mRNA, the hybridization of VEGF mRNA destroyed the stem-loop conformation of MB, and then, the two fluorophores labeled on MB were separated with low FRET efficiency. This constructed fluorescent nanoprobe enables the quantitative analysis and in situ imaging of the VEGF mRNA level in living cells under hypoxic conditions. We expect that it will offer a potentially rich opportunity to understand the physiological processes of genetic programme.