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WIREs Nanomed Nanobiotechnol
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Functional carbon nanodots for multiscale imaging and therapy

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As an emerging class of carbon nanomaterials, carbon dots (CDs) have garnered many researchers’ interests in the past decade due to their excellent biocompatibility, replete surface functional groups, water dispersibility, and unique photoluminescence. These extraordinary properties have opened new avenues for their advanced application in cell labeling, bioimaging, drug delivery, sensors, and energy‐related devices. In this paper, we critically review recent advances in the synthetic strategies and the application of CDs for biological purposes, specifically, imaging and therapy. Finally, a perspective has been given on the potential challenges facing the translation of these materials from the bench to the market. WIREs Nanomed Nanobiotechnol 2017, 9:e1436. doi: 10.1002/wnan.1436 This article is categorized under: Diagnostic Tools > In Vitro Nanoparticle-Based Sensing
Versatile application of carbon dots for biomedical applications.
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In vivo treatment of the MCF‐7 tumor bearing mice with a STAT‐3 inhibitor delivered via the host–guest chemistry approach on the surface of the carbon nanoparticles (CNPs). Panel (a) shows the treatment stages. Panels (c), (e), and (g) represent the mice treated with saline, CB[6] drug (CB6 Nic) and CNPs decorated with CB[6] delivering the drug (CB6 CNP Nic), respectively. A size reduction in the tumor is visible according to the data in (h–j). Panels (k), (l), and (m) show the H&E staining of the tumor tissue treated with saline, CB6 Nic and CB6 CNP Nic where the cell apoptosis is readily observed. (Reprinted with permission from Ref . Copyright 2016 John Wiley and sons)
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Proof of concept experiment of using carbon dots (CDs) for Raman tissue imaging. (a) The pig's skin was incubated with near‐infrared fluorescent CDs and was subsequently imaged using Raman vibrational imaging. Panel (a) shows the schematics of the experiment indicating that after the injection of the nanoparticles to the skin, Raman imaging can be used to identify the chemical signatures on the surface while fluorescent imaging can indicate the imaging in‐depth. (b) The average Raman spectrum of the I treated and II untreated skin with CDs. Panels (c) and (d) represent the image formed by the integration of the C − H peak (2900 cm−1) of the treated and untreated pig skin, respectively. Panels (e) and (f) are the corresponding 3D light sheet fluorescence images of untreated and treated samples demonstrating an enhancement of 100 µm inside the skin surface. LCN stands for luminescent carbon nanoparticles. (Reprinted with permission from Ref . Copyright 2015 John Wiley and Sons)
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Photoacoustic imaging using honey‐derived carbon dots (CDs). (a) Red indicates the optical absorbance from blood. Blood vessel (BV), lymph vessel (LV), and sentinel lymph node (SLN) are shown by arrows. (b) The 3D photoacoustic image after CD injection. Panel (c) shows the accumulation of CDs in SLN. (Reprinted with permission from Ref . Copyright 2013 Springer Science+Business Media)
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The proof of concept study on the application of hyperspectral imaging for the tracking of the drug‐loaded carbon dots (CDs) for quantitative and visualization assessments inside the cells (MCF‐7). Panels (a, b) indicate that signal from the drug‐loaded CDs could be detected in this imaging modality. These are the 3D demonstration. (c) Side view, (d) top view, (e) horizontal axis of the same. (f–j) are the same as (a–e) where the cellular features have been removed for better clarity. The arrows point to the location of the CD‐loaded drugs in the cells. (Reprinted with permission from Ref . Copyright 2016 John Wiley and Sons)
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In vitro and in vivo imaging with CDS. (a) and (b) Two‐photon luminescence image (800 nm excitation) of human ER(+) breast cancer MCF‐7 cells with internalized carbon dots (CDs); in vivo fluorescence imaging of CDs in athymic nude mice using the near‐infrared (NIR) emitting CDs under various excitation wavelengths. Green is the autofluorescence signal from skin while red is the signal from CDs. The animals were injected subcutaneously with the nanoparticles in three different sites as has been delineated with numbers. (k) The separation of signal from background taken under NIR (704 nm) excitation demonstrating the distinct signals from CDs and enhanced signal: noise due to the attenuation of the autofluorescence from the tissue making the overall ratio more pronounced. (1) represents the signal from the nanoparticles and (2) is the signal from the autofluorescence. (Reprinted with permission from Ref . Copyright 2012 John Wiley and Sons)
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Physicochemical characters of carbon dots (CDs). (a), (b), and (c) Typical Transmission Electron Microscopy (TEM) images of the CDs indicating semispherical morphology. In this case, carbon dots were prepared from modified thermal pyrolysis using citric acid as carbon source and polyene polyamine as passivation agent. (d) The Atomic Force Microscopy (AFM) height profile of the same particles. (Reprinted with permission from Ref . Copyright 2014 John Wiley and Sons) (e) Excitation‐dependent emission of CDs; red, black, green, and blue curves correspond to the photoluminescence spectra for blue‐, green‐, yellow‐, and red‐emitting CDs, respectively. (f) The corresponding optical images under visible (left) and UV light (right: 365 nm). (Reprinted with permission from Ref . Copyright 2010 John Wiley and Sons)
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