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WIREs Nanomed Nanobiotechnol
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Emerging two‐dimensional monoelemental materials (Xenes): Fabrication, modification, and applications thereof in the field of bioimaging as nanocarriers

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Abstract In recent years, more and more research enthusiasm has been devoted to the development of emerging two‐dimensional (2D) monoelement materials (Xenes) and explored potential applications in various fields, especially biomedicine and bioimaging. The inspiring results attribute to their excellent physicochemical properties, including adjustable band gap, surface electronic layout characteristics, and so on, making it easier for surface modification in order to meet designated needs. As a popular interdisciplinary research frontier, a variety of methods for fabricating 2D Xenes have recently been adopted for pre‐preparing future practical bioimaging applications, which implies that these materials will have broad clinical application prospects in the future. In this review, we will concentrate on the family of 2D Xenes and summarize their fabrication and modification methods firstly. Then, their applications in bioimaging as nanocarriers will be described according to the Periodic Table of Elements. In addition, current challenges and prospects for further clinical applications will be under discussion and use black phosphorus as a typical example. At last, general conclusion will be made that it is worth expecting that 2D Xenes will play a key role in the next generation of oncologic bioimaging in the future. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease Toxicology and Regulatory Issues in Nanomedicine > Toxicology of Nanomaterials Toxicology and Regulatory Issues in Nanomedicine > Regulatory and Policy Issues in Nanomedicine
Schematic of the classification, fabrication methods and applications of 2D Xenes in bioimaging
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Tumor imaging dealing with AM‐PEG/DOX NS. (a) Illustration of synthetic 2D AM‐PEG/DOX NS. (b) in vivo fluorescence imaging of tumors at different time points postinjection with Cy5.5‐labeled AM‐PEG NSs. (c) Ex vivo fluorescence imaging of the tumor tissue and major organs at 24 h postinjection. (d) Semiquantitative biodistribution of Cy5.5‐labeled AM‐PEG NSs by the average fluorescence intensity of tumors and major organs per gram. (e) in vivo PA imaging of tumors postinjection with AM‐PEG NSs. (f) Quantitative analysis of each ROI signal in (e). (g) PT imaging after different treatments (Group 1: Saline; Group 2: DOX; Group 3: AM‐PEG/DOX NSs; Group 4: AM‐PEG NSs + NIR; and Group 5: AM‐PEG/DOX NSs + NIR). Adapted from Farokhzad et al. (2018). Copyright 2018, Wiley‐VCH. Biodistribution and clearance of AMNFs in organs of tumor‐bearing mice. (h) Top panel: 3D reconstruction of the photoacoustic signal in liver and kidney pre‐ and postinjection at different time points. Bottom panel: Histogram plot of the photoacoustic signal at different time points. (i) Histogram plot of photoacoustic signal of various organs obtained from the MCF‐7 bearing mice at 24 h postinjection. In vivo photoacoustic imaging of tumor in a mouse model. (j) 3D reconstruction of photoacoustic signal at the tumor site pre‐ and post‐systematically admission of AMNFs (a representative of three parallel experimental mice). (k) Statistical analysis of the obtained photoacoustic signal at different time points. Adapted from Wang et al. (2019). Copyright 2019, Wiley‐VCH. Bioimaging of Sb–THPP–PEG NS. (l) in vivo infrared thermal images of MCF‐7 tumor‐bearing mice postinjection of various materials with various treatment. Group 1: PBS; Group 2: PBS + 660 nm + 808 nm; Group 3: THPP+660 nm; Group 4: Sb–PEG NS + 808 nm; Group 5: Sb–THPP–PEG NS + 660 nm; Group 6: Sb–THPP–PEG NS + 808 nm; Group 7: Sb–THPP–PEG NS + 660 nm + 808 nm. (m) In vivo fluorescence images of MCF‐7 tumor‐bearing mice at different time after intravenous injection of Sb–THPP–PEG NSs. (n) Fluorescence images of tumor and major organs after postinjection of 24 h. (o) Quantitative fluorescence intensity determination of Sb–THPP–PEG NSs in major organs and tumor tissues. (p) In vivo real‐time photoacoustic imaging of MCF‐7 tumor‐bearing mice after intravenous injection with Sb–THPP–PEG NSs. Adapted from Zhang et al. (2021). Copyright 2021, Wiley‐VCH
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Tumor imaging dealing with BP‐based nanocomposites. (a) In vivo PA imaging of the 4 T1 tumor‐bearing mice at different time points. (b) PT imaging of tumors after injection of BP‐DEX/PEI‐FA/Cy7 solution or PBS and NIR irradiation. (c) in vivo fluorescence imaging of tissues before and after injection. Adapted from Li, Jing, et al. (2018). Copyright 2018, Elsevier B.V. and Science China Press. In vivo PA imaging of BPQD vesicles. (d) PA imaging of tumor location at different time (1) without and (2) with laser irradiation. (e) The PA amplitudes of tumors at different postinjection time points. (f) PA imaging of tumor location at different depths 24 h postinjection, and (g) the corresponding PA amplitudes originating from (f). Adapted from Yang et al. (2019). Copyright 2019, Wiley‐VCH. Photothermal imaging and biodegradation performance of BPQD/PLGA. (h) Photothermal imaging after intravenous injection. (i) Residual weight of the BPQDs/PLGA NSs after degradation in PBS. (j) SEM imaging of the BPQDs/PLGA NSs after degradation in PBS at different time together with the corresponding TEM image after degradation for 8 weeks. (k) Schematic illustration for the degradation process. Adapted from Chu et al. (2016)
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Tumor imaging of [email protected] (a) In vitro PA imaging of solution and in vivo PA imaging of the tumor location at different time. (b) Linear relationship between the concentrations and the PA signals in (a). (c) Quantitative analysis of PA signals originating from tumors in (a). (d) PT imaging of mice (G1: Control; G2: NIR; G3: [email protected]; G4: [email protected]+NIR). Adapted from Farokhzad et al. (2019). Copyright 2019, Wiley‐VCH. In vivo imaging of the [email protected] NS. (e) Time‐dependent in vivo fluorescence imaging of mice after intravenous injection of Cy5.5‐[email protected] NS. Red circles represent tumor regions. (f) Fluorescence images of main organs and tumor excised from mice 8 h after intravenous injection. I–VI represent heart, spleen, lung, liver, kidney and tumor, respectively. (g) Quantitative fluorescence intensity of the tissues in image (f). (h) PA images of the tumor tissues excised from mice at predetermined time points after intravenous injection. (i) PT imaging of tumor‐bearing mice with different treatments. G1, control; G2, NIR; G3, [email protected] NS without NIR; G4, [email protected] NS with NIR. NIR, 808 nm laser (1 W/cm2, 5 min). NIR irradiation was executed 8 h after intravenous injection. Adapted from Tao et al. (2020). Copyright 2020, Elsevier
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Multi‐modality imaging after dealing with GO/BaGdF5/PEG. (a) Time‐dependent T1‐weighted MR imaging of tumor location postinjection of GO/BaGdF5/PEG. (b) Photothermal imaging of tumor tissue postinjection with (a1) or without (a2) GO/BaGdF5/PEG dealing with NIR irradiation. (c) CT imaging of tumor location before and after injection of GO/BaGdF5/PEG. (d) the 3D CT imaging before and after injection of GO/BaGdF5/PEG. Adapted from Yang et al. (2015). Copyright 2014, Elsevier. Multi‐modality imaging after dealing with rGO‐IONP‐PEG. (e) Fluorescence imaging using Cy5 labeled rGO–IONP–PEG; (f) T2‐weighted MR imaging and (g) photoacoustic imaging using rGO–IONP–PEG. (h) MR images of rGO–IONP–PEG injected mice with (the upper low) and without (the lower row) laser irradiation. Arrows point the tumor sites. Adapted from Liu et al. (2012). Copyright 2012, Wiley‐VCH
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Tumor imaging dealing with B NS‐based nanocomposites. (a) Schematic illustration of the designed B‐PEG/DOX nanosheets. (b) Ex vivo fluorescence imaging of the tumor tissue and main organs 24 h postinjection of the designed nanosheets. (c) PA imaging of the tumor location at different time. (d) Photothermal imaging dealing with several groups (Group 1: Saline; Group 2: DOX; Group 3: DOX/B‐PEG NSs; Group 4: B‐PEG NSs + NIR; Group 5: DOX/B‐PEG NSs + NIR). Adapted from Shi et al. (2018). Copyright 2018, Wiley‐VCH
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Schematic diagram of the common synthetic methods for Xenes: (a) bottom‐up fabrication and (b) top‐down fabrication
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The corresponding structures for Xenes from different groups. (a) Group III: Borophene. (b) Group VI: Tellurophene. (c) Group IV: Graphene and its derivates. (d) Group V: Arsenene and black phosphorous (α phase), and (e) Arsenene, black phosphorous and Antimonene (β phase)
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Toxicology and Regulatory Issues in Nanomedicine > Regulatory and Policy Issues in Nanomedicine
Toxicology and Regulatory Issues in Nanomedicine > Toxicology of Nanomaterials
Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease

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