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      Cell Nucleus-Targeting Zwitterionic Carbon Dots

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      1 , 1 , a , 1 , 2
      Scientific Reports
      Nature Publishing Group

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          Abstract

          An innovative nucleus-targeting zwitterionic carbon dot (CD) vehicle has been developed for anticancer drug delivery and optical monitoring. The zwitterionic functional groups of the CDs introduced by a simple one-step synthesis using β-alanine as a passivating and zwitterionic ligand allow cytoplasmic uptake and subsequent nuclear translocation of the CDs. Moreover, multicolor fluorescence improves the accuracy of the CDs as an optical code. The CD-based drug delivery system constructed by non-covalent grafting of doxorubicin, exhibits superior antitumor efficacy owing to enhanced nuclear delivery in vitro and tumor accumulation in vivo, resulting in highly effective tumor growth inhibition. Since the zwitterionic CDs are highly biocompatible and effectively translocated into the nucleus, it provides a compelling solution to a multifunctional nanoparticle for substantially enhanced nuclear uptake of drugs and optical monitoring of translocation.

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          Most cited references34

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          Cellular uptake, intracellular trafficking, and cytotoxicity of nanomaterials.

          The interactions of nanoparticles with the soft surfaces of biological systems like cells play key roles in executing their biomedical functions and in toxicity. The discovery or design of new biomedical functions, or the prediction of the toxicological consequences of nanoparticles in vivo, first require knowledge of the interplay processes of the nanoparticles with the target cells. This article focusses on the cellular uptake, location and translocation, and any biological consequences, such as cytotoxicity, of the most widely studied and used nanoparticles, such as carbon-based nanoparticles, metallic nanoparticles, and quantum dots. The relevance of the size and shape, composition, charge, and surface chemistry of the nanoparticles in cells is considered. The intracellular uptake pathways of the nanoparticles and the cellular responses, with potential signaling pathways activated by nanoparticle interactions, are also discussed. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
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            DNA and its associated processes as targets for cancer therapy.

            DNA is the molecular target for many of the drugs that are used in cancer therapeutics, and is viewed as a non-specific target of cytotoxic agents. Although this is true for traditional chemotherapeutics, other agents that were discovered more recently have shown enhanced efficacy. Furthermore, a new generation of agents that target DNA-associated processes are anticipated to be far more specific and effective. How have these agents evolved, and what are their molecular targets?
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              Nano-carrier for gene delivery and bioimaging based on carbon dots with PEI-passivation enhanced fluorescence.

              Polyethylenimine (PEI) functionalized carbon dots (CD-PEI) were fabricated by one-step microwave assisted pyrolysis of glycerol and branched PEI25k mixture where the formation of carbon nanoparticles and the surface passivation were accomplished simultaneously. In this hybrid C-dot, PEI molecule played two key roles in the system - as a nitrogen-rich compound to passivate surface to enhance the fluorescence and as a polyelectrolyte to condense DNA. This CD-PEI was shown to be water soluble and emit stable bright multicolor fluorescence relying on excitation wavelength. The DNA condensation capability and cytotoxicity of CD-PEI could be regulated by pyrolysis time possibly due to the somewhat destruction of PEI during the formation of carbon dots. CD-PEI obtained at an appropriate pyrolysis time exhibited lower toxicity, higher or comparable gene expression of plasmid DNA in COS-7 cells and HepG2 cells relative to control PEI25k. Intriguingly, the CD-PEIs internalized into cells displayed tunable fluorescent emission under varying excitation wavelength, suggesting the potential application of CD-PEI in gene delivery and bioimaging. Copyright © 2012 Elsevier Ltd. All rights reserved.
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                Author and article information

                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group
                2045-2322
                22 December 2015
                2015
                : 5
                : 18807
                Affiliations
                [1 ]Department of Chemistry, Ulsan National Institute of Science and Technology (UNIST), UNIST-gil 50 , Ulsan 689-798, Republic of Korea
                [2 ]Department of Energy Engineering, Ulsan National Institute of Science and Technology (UNIST), UNIST-gil 50 , Ulsan 689-798, Republic of Korea
                Author notes
                Article
                srep18807
                10.1038/srep18807
                4686939
                26689549
                f73d80fd-d6dd-438d-81a7-963f4803bb2e
                Copyright © 2015, Macmillan Publishers Limited

                This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

                History
                : 20 July 2015
                : 25 November 2015
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