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WIREs Nanomed Nanobiotechnol
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Two‐dimensional metal organic frameworks for biomedical applications

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Abstract Two‐dimensional (2D) metal organic frameworks (MOFs), are an emerging class of layered nanomaterials with well‐defined structure and modular composition. The unique pore structure, high flexibility, tunability, and ability to introduce desired functionality within the structural framework, have led to potential use of MOFs in biomedical applications. This article critically reviews the application of 2D MOFs for therapeutic delivery, tissue engineering, bioimaging, and biosensing. Further, discussion on the challenges and strategies in next generation of 2D MOFs are also included. This article is categorized under: Nanotechnology Approaches to Biology > Nanoscale Systems in Biology
2D MOFs. (a) Metal ions connected by organic linkers to form 2D MOF structures. (b) Number of publications since 2010, when keywords “2D MOFs” were used, indicating the recent increasing popularity of 2D MOFs (data obtained December 2019). (c) Overview of different biomedical applications of 2D MOFs. (d) Number of publications since 2010, when keywords “2D MOFs” and different biomedical application keywords were used like “drug delivery,” “biosensing,” “bioimaging,” and “tissue engineering” (data obtained December 2019)
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MOFs loaded scaffolds used to ablate bone tumors and promote osteogenesis at the defect site. (a) Scheme of fabrication of 3D printed TCP scaffolds and in situ growth of Cu‐TCCP nanosheets on the surface of the scaffold. (b) Cu‐TCCP‐TCP scaffolds enabled killing of bone tumor cells using the thermal energy generated upon NIR light activation and also promoted osteogenesis at the bone defect site because of release of bioactive ions Cu2+, PO43−, and Ca2+. Created with BioRender.com
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Fabrication of tunable hydrogel‐MOF composites by 3D printing hydrogel MOF precursor mixture followed by UV curing of the printed structure. The cured structure was then ionically crosslinked in Cu(NO3)2 solution to facilitate in situ synthesis of HKUST to yield hydrogel‐MOF composites. (Reprinted with permission from Liu et al. (2020). Copyright 2020, American Chemical Society)
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2D MOF‐based sensor arrays. (a) Scheme of 2D MOF nanozyme sensor arrays to discriminate phosphates. (b) Catalytic activity with the nanozymes were differentially modulated based on the presence of different phosphates. (Reprinted with permission from Qin et al. (2018). Copyright 2018, Analytical Chemistry)
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2D MOFs for bioimaging applications. (a) Schematic representation of radioactive isotope‐tagged 2D MOFs for bioimaging. (b) in vivo SPECT images of tumor‐bearing Balb/c mice post i.v. injection of 99mTc‐Hf‐TCPP MOFs. (c) Quantitative distribution of the MOFs in tumor, liver, kidney, and muscle. (Reprinted with permission from Zhu et al. (2018). Copyright 2019, Coordination Chemistry Reviews)
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2D MOFs for photodynamic therapy (PDT). (a) Scheme for the synthesis of hafnium‐and porphyrin‐based MOF. (b) TEM image of DBP‐UiO MOF with nanoplate morphology. (c) PDT caused improved tumor growth inhibition in mice treated with DBP‐UiO MOFs. (d) DBP‐UiO MOFs resulted in tumor size shrinkage after 8 days of PDT treatment. (Reproduced with permission from Schellenberg et al. (2014). Copyright 2014, Journal of the American Chemical Society)
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2D MOFs used for drug delivery applications. (a) Schematic representation of 2D MOFs used for delivery of cisplatin and Cu into the cancer cells. (b) Accumulated release of cisplatin from Cu‐TCPP(Fe) nanosheets at pH 5.0 and 7.4. (c) Significant reduction in viability of A549 cells were observed upon treatment with Cu‐TCPP(Fe) compared to that of cells treated with free cisplatin (Li et al., 2018). Copyright 2018, American Chemical Society
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2D MOFs‐based nanozyme. (a) Scheme representing the synthesis of 2D Zn‐TCPP nanosheets. (b) Scheme representing the use of 2D MOF nanosheets with peroxidase activity to monitor the elimination of heparin in vivo. (c) Kinetic assay with time‐dependent fluorescence intensity indicating increased activation of 2D nanosheets that is modified with anti‐heparin peptide, AG73, in heparin‐treated rats. (d) Heparin elimination was tracked by monitoring the heparin concentrations in the artery of live rats for 4 hr after heparin administration. (Reprinted with permission from Cheng et al. (2017). Copyright 2017, Analytical Chemistry)
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Surface engineering of 2D MOFs. (a) Schematic illustration of functionalization of 2D MOFs with chitosan. (b) List of common ligands that are used to functionalize 2D MOFs. Created with BioRender.com
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Overview of top‐down and bottom‐up approaches for synthesis of 2D MOFs
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