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Toxicology of chemically modified graphene-based materials for medical application.

Nezakati T, Cousins BG, Seifalian AM - Arch. Toxicol. (2014)

Bottom Line: Graphene is one of the most promising nanomaterials due to unique physicochemical properties including enhanced optical, thermal, and electrically conductive behavior in addition to mechanical strength and high surface-to-volume ratio.Several studies investigating important material properties such as surface charge, concentration, shape, size, structural defects, and chemical functional groups relate to their safety profile and influence cyto- and geno-toxicology.The advent of graphene technology has led to many promising new opportunities for future applications in the field of electronics, biotechnology, and nanomedicine to aid in the diagnosis and treatment of a variety of debilitating diseases.

View Article: PubMed Central - PubMed

Affiliation: UCL Centre for Nanotechnology and Regeneration Medicine, Division of Surgery and Interventional Science, University College London, London, UK, toktam.nezakati.11@ucl.ac.uk.

ABSTRACT
This review article aims to provide an overview of chemically modified graphene, and graphene oxide (GO), and their impact on toxicology when present in biological systems. Graphene is one of the most promising nanomaterials due to unique physicochemical properties including enhanced optical, thermal, and electrically conductive behavior in addition to mechanical strength and high surface-to-volume ratio. Graphene-based nanomaterials have received much attention over the last 5 years in the biomedical field ranging from their use as polymeric conduits for nerve regeneration, carriers for targeted drug delivery and in the treatment of cancer via photo-thermal therapy. Both in vitro and in vivo biological studies of graphene-based nanomaterials help understand their relative toxicity and biocompatibility when used for biomedical applications. Several studies investigating important material properties such as surface charge, concentration, shape, size, structural defects, and chemical functional groups relate to their safety profile and influence cyto- and geno-toxicology. In this review, we highlight the most recent studies of graphene-based nanomaterials and outline their unique properties, which determine their interactions under a range of environmental conditions. The advent of graphene technology has led to many promising new opportunities for future applications in the field of electronics, biotechnology, and nanomedicine to aid in the diagnosis and treatment of a variety of debilitating diseases.

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Schematic diagram of the procedure for GO–PEI–UNCP: Numbers of core-shell structured UCNPs covalently grafted with GO through polyethylenimine for advanced imaging, drug delivery, and photo-thermal therapy
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Fig4: Schematic diagram of the procedure for GO–PEI–UNCP: Numbers of core-shell structured UCNPs covalently grafted with GO through polyethylenimine for advanced imaging, drug delivery, and photo-thermal therapy

Mentions: Photo-thermal therapy (PTT) converts light or optical energy to heat by absorption of a range of nanomaterial (e.g., silica-coated gold nanoparticles), leading to the thermal ablation resulting in the death of cancer cells. In recent years, PTT as a minimally invasive, controllable, and highly efficient treatment method has drawn widespread attention in the treatment of cancer. A large number of research groups have developed various light-absorbing nanomaterials as PTT agents (Huang et al. 2006; Chen et al. 2007; Yavuz et al. 2009; Wu et al. 2010; Dong et al. 2011; Tian et al. 2011; Cheng et al. 2011, 2012; Yang et al. 2010, 2012b, c; Moon et al. 2009; Liu et al. 2011; Wang et al. 2011, 2012), all with absorbance values in the near-infrared (NIR) region (560–760 nm), which is the region ideal for controlling interactions with biological tissues. Despite the great promise of PTT in cancer treatment using nanomaterials, the development of a new generation of PTT agents with enhanced NIR absorption and multiple functions to realize imaging-guided highly effective cancer therapy still merits further effort. Carbon-based nanomaterials, such as CNTs, carbon nanohorns, and graphene, are being extensively studied as potential PTT agents (Moon et al. 2009; Liu et al. 2011; Wang et al. 2011, 2012; Yang et al. 2010, 2012b). Besides inorganic materials, organic nanoparticles, such as polypyrrole and other light-absorbing conductive polymers, have also shown potential in PTT cancer ablation in a few recent studies (Cheng et al. 2012; Yang et al. 2012c; Chen et al. 2012c; Zha et al. 2013). Nanoparticle-based NIR-PTT provides an encouraging remedy and strategy for efficient tumor ablation with minimum injury to the surrounding tissues. Up-conversion of nanoparticles (UCNPs) is a further approach to PTT. As an example, UNCP, water-dispersible nanocrystals, which is fluorophores and magnetic nanoparticles, whereby ferric oxide (Fe3O4) is reacted with polyethylenimine-modified GO (PEI-GO) acting as a nanocarrier attached to the nanocrystals to yield PEI-GO–nanocrystal (Yan et al. 2013). PEI-GO–UCNP is able to load water-insoluble anticancer drugs, such as doxorubicin (DOX), with a superior loading capacity of 100 wt%, through hydrophobic, π–π stacking interaction between PEI-GO–UCNP, and an aromatic drug highlighted in Fig. 4. Chemotherapy and PTT when used in combination have been proven to reduce drug resistance, and to be an effective strategy to improve the cancer therapy efficacy (Tang et al. 2010; Tang and Mcgoron 2009; Hauck et al. 2008; Lee et al. 2010). In contrast, undesired damage to normal tissues may be caused by non-specific, untargeted drug delivery and heat supplied to the tumor area. Moreover, recent studies suggest that graphene possesses a higher photo-thermal sensitivity than CNTs, and is more effective in PTT in the treatment of cancer (Markovic et al. 2011; Yang et al. 2010, 2012a; Tian et al. 2011).Fig. 4


Toxicology of chemically modified graphene-based materials for medical application.

Nezakati T, Cousins BG, Seifalian AM - Arch. Toxicol. (2014)

Schematic diagram of the procedure for GO–PEI–UNCP: Numbers of core-shell structured UCNPs covalently grafted with GO through polyethylenimine for advanced imaging, drug delivery, and photo-thermal therapy
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4201927&req=5

Fig4: Schematic diagram of the procedure for GO–PEI–UNCP: Numbers of core-shell structured UCNPs covalently grafted with GO through polyethylenimine for advanced imaging, drug delivery, and photo-thermal therapy
Mentions: Photo-thermal therapy (PTT) converts light or optical energy to heat by absorption of a range of nanomaterial (e.g., silica-coated gold nanoparticles), leading to the thermal ablation resulting in the death of cancer cells. In recent years, PTT as a minimally invasive, controllable, and highly efficient treatment method has drawn widespread attention in the treatment of cancer. A large number of research groups have developed various light-absorbing nanomaterials as PTT agents (Huang et al. 2006; Chen et al. 2007; Yavuz et al. 2009; Wu et al. 2010; Dong et al. 2011; Tian et al. 2011; Cheng et al. 2011, 2012; Yang et al. 2010, 2012b, c; Moon et al. 2009; Liu et al. 2011; Wang et al. 2011, 2012), all with absorbance values in the near-infrared (NIR) region (560–760 nm), which is the region ideal for controlling interactions with biological tissues. Despite the great promise of PTT in cancer treatment using nanomaterials, the development of a new generation of PTT agents with enhanced NIR absorption and multiple functions to realize imaging-guided highly effective cancer therapy still merits further effort. Carbon-based nanomaterials, such as CNTs, carbon nanohorns, and graphene, are being extensively studied as potential PTT agents (Moon et al. 2009; Liu et al. 2011; Wang et al. 2011, 2012; Yang et al. 2010, 2012b). Besides inorganic materials, organic nanoparticles, such as polypyrrole and other light-absorbing conductive polymers, have also shown potential in PTT cancer ablation in a few recent studies (Cheng et al. 2012; Yang et al. 2012c; Chen et al. 2012c; Zha et al. 2013). Nanoparticle-based NIR-PTT provides an encouraging remedy and strategy for efficient tumor ablation with minimum injury to the surrounding tissues. Up-conversion of nanoparticles (UCNPs) is a further approach to PTT. As an example, UNCP, water-dispersible nanocrystals, which is fluorophores and magnetic nanoparticles, whereby ferric oxide (Fe3O4) is reacted with polyethylenimine-modified GO (PEI-GO) acting as a nanocarrier attached to the nanocrystals to yield PEI-GO–nanocrystal (Yan et al. 2013). PEI-GO–UCNP is able to load water-insoluble anticancer drugs, such as doxorubicin (DOX), with a superior loading capacity of 100 wt%, through hydrophobic, π–π stacking interaction between PEI-GO–UCNP, and an aromatic drug highlighted in Fig. 4. Chemotherapy and PTT when used in combination have been proven to reduce drug resistance, and to be an effective strategy to improve the cancer therapy efficacy (Tang et al. 2010; Tang and Mcgoron 2009; Hauck et al. 2008; Lee et al. 2010). In contrast, undesired damage to normal tissues may be caused by non-specific, untargeted drug delivery and heat supplied to the tumor area. Moreover, recent studies suggest that graphene possesses a higher photo-thermal sensitivity than CNTs, and is more effective in PTT in the treatment of cancer (Markovic et al. 2011; Yang et al. 2010, 2012a; Tian et al. 2011).Fig. 4

Bottom Line: Graphene is one of the most promising nanomaterials due to unique physicochemical properties including enhanced optical, thermal, and electrically conductive behavior in addition to mechanical strength and high surface-to-volume ratio.Several studies investigating important material properties such as surface charge, concentration, shape, size, structural defects, and chemical functional groups relate to their safety profile and influence cyto- and geno-toxicology.The advent of graphene technology has led to many promising new opportunities for future applications in the field of electronics, biotechnology, and nanomedicine to aid in the diagnosis and treatment of a variety of debilitating diseases.

View Article: PubMed Central - PubMed

Affiliation: UCL Centre for Nanotechnology and Regeneration Medicine, Division of Surgery and Interventional Science, University College London, London, UK, toktam.nezakati.11@ucl.ac.uk.

ABSTRACT
This review article aims to provide an overview of chemically modified graphene, and graphene oxide (GO), and their impact on toxicology when present in biological systems. Graphene is one of the most promising nanomaterials due to unique physicochemical properties including enhanced optical, thermal, and electrically conductive behavior in addition to mechanical strength and high surface-to-volume ratio. Graphene-based nanomaterials have received much attention over the last 5 years in the biomedical field ranging from their use as polymeric conduits for nerve regeneration, carriers for targeted drug delivery and in the treatment of cancer via photo-thermal therapy. Both in vitro and in vivo biological studies of graphene-based nanomaterials help understand their relative toxicity and biocompatibility when used for biomedical applications. Several studies investigating important material properties such as surface charge, concentration, shape, size, structural defects, and chemical functional groups relate to their safety profile and influence cyto- and geno-toxicology. In this review, we highlight the most recent studies of graphene-based nanomaterials and outline their unique properties, which determine their interactions under a range of environmental conditions. The advent of graphene technology has led to many promising new opportunities for future applications in the field of electronics, biotechnology, and nanomedicine to aid in the diagnosis and treatment of a variety of debilitating diseases.

Show MeSH
Related in: MedlinePlus