Alberto Bianco

The University of Manchester, Manchester, England, United Kingdom

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Publications (210)1262.68 Total impact

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    ABSTRACT: Given the promise of carbon nanotubes (CNTs) for photothermal therapy, drug delivery, tissue engineering, and gene therapy, there is a need for non-invasive imaging methods to monitor CNT distribution and fate in the body. In this study, non-ionizing whole-body high field magnetic resonance imaging (MRI) is used to follow the distribution of water-dispersible non-toxic functionalized CNTs administrated intravenously to mice. Oxidized CNTs are endowed with positive MRI contrast properties by covalent functionalization with the chelating ligand diethylenetriaminepentaacetic dianhydride (DTPA), followed by chelation to Gd3+. The structural and magnetic properties, MR relaxivities, cellular uptake, and application for MRI cell imaging of Gd-CNTs in comparison to the precursor oxidized CNTs are evaluated. Despite the intrinsic T2 contrast of oxidized CNTs internalized in macrophages, the anchoring of paramagnetic gadolinium onto the nanotube sidewall allows efficient T1 contrast and MR signal enhancement, which is preserved after CNT internalization by cells. Hence, due to their high dispersibility, Gd-CNTs have the potential to produce positive contrast in vivo following injection into the bloodstream. The uptake of Gd-CNTs in the liver and spleen is assessed using MRI, while rapid renal clearance of extracellular Gd-CNTs is observed, confirming the evidences of other studies using different imaging modalities.
    Advanced Functional Materials 09/2014; · 10.44 Impact Factor
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    ABSTRACT: Carbon nanotubes (CNTs) exhibit unique properties which have led to their applications in the biomedical field as novel delivery systems for diagnosis and therapy purposes. We have previously reported that the degree of functionalization of CNTs is a key factor determining their biological behaviour. The present study broadens the spectrum by investigating the impact of the diameter of CNTs using two series of multi-walled CNTs (MWNTs) with distinct differences in their diameters. Both MWNTs were doubly functionalized by 1,3-dipolar cycloaddition and amidation reactions, allowing the appended functional groups to be further conjugated with radionuclide chelating moieties and antibodies or antibody fragments. All constructs possessed comparable degree of functionalization and were characterized by thermogravimetric analysis, transmission electron microscopy, gel electrophoresis and surface plasmon resonance. The MWNT conjugates were radio-labelled with indium-111, which thereby enabled in vivo single photon emission computed tomography/computed tomography (SPECT/CT) imaging and organ biodistribution study using γ-scintigraphy. The narrow MWNTs (average diameter: 9.2 nm) demonstrated enhanced tissue affinity including non-reticular endothelial tissues compared to the wider MWNTs (average diameter: 39.5 nm). The results indicate that the higher aspect ratio of narrow MWNTs may be beneficial for their future biological applications due to higher tissue accumulation.
    Biomaterials 08/2014; · 8.31 Impact Factor
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    ABSTRACT: Carbon nanotubes (CNTs) are recognized as promising nanomaterials for technological advancement. However, the stigma of structural similarity with asbestos fibers has slowed down progress of CNTs in nanomedicine. Nevertheless, it also prompted thorough studies that have revealed that functionalized CNTs (fCNTs) can biologically behave in a very different and safer manner. Here we review pristine and fCNT fate in biological settings, focusing on the importance of protein interaction, formation of the protein corona, and modulation of immune response. The emerging consensus on the desirable fCNT properties to achieve immunological neutrality, and even biodegradation, shows great promise for CNT adoption in medicine.
    Materials Today 08/2014; · 6.07 Impact Factor
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    ABSTRACT: Spaceflights lead to dysregulation of the immune cell functionality affecting the expression of activation markers and cytokine production. Short oxidized multi-walled carbon nanotubes functionalized by 1,3-dipolar cycloaddition have been reported to activate immune cells. In this Communication we have performed surface marker assays and multiplex ELISA on primary monocytes and T cells under microgravity. We have discovered that carbon nanotubes, through their immunostimulatory properties, are able to fight spaceflight immune system dysregulations.
    Nanoscale 07/2014; · 6.73 Impact Factor
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    ABSTRACT: Carbon-based nanomaterials, including carbon nanotubes and graphene, have created great attention in the scientific community for their unique physico-chemical properties, which could be also promising in many biomedical-related fields. In particular, their low cytotoxicity, achieved when properly functionalized, along with the possibility to link multiple bioactive molecules, realistically allows envisaging their potential use as therapeutic platform. In this context, the immune system and immune responses play an important role in our organism, as they are involved either directly or indirectly in many diseases. Therefore, the possibility to prevent or block a disease by controlling and/or modulating the immune responses has become one important task in nanomedicine. In this feature article the advantages to use carbon-based materials in immunotherapy are presented. Important goals obtained using carbon nanotubes and graphene are described, highlighting the promising use of these nanomaterials in cancer treatment, imaging and vaccine development. The capacity of functionalized carbon nanotubes to modulate the immune responses is also discussed, highlighting the current state of the art and the future developments on this subject.
    J. Mater. Chem. B. 07/2014;
  • ChemInform 06/2014; 45(23).
  • Angewandte Chemie 06/2014;
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    ABSTRACT: Graphing graphene: Because the naming of graphene-based materials (GBMs) has led to confusion and inconsistency, a classification approach is necessary. Three physical-chemical properties of GBMs have been defined by the GRAPHENE Flagship Project of the European Union for the unequivocal classification of these materials (see grid).
    Angewandte Chemie International Edition in English 06/2014; · 13.45 Impact Factor
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    ABSTRACT: It has been recently proposed that nanomaterials, alone or in concert with their specific biomolecular conjugates, can be used to directly modulate the immune system, therefore offering a new tool for the enhancement of immune-based therapies against infectious disease and cancer. Here, we revised the publications on the impact of functionalized carbon nanotubes (f-CNTs), graphene and carbon nanohorns on immune cells. Whereas f-CNTs are the nanomaterial most widely investigated, we noticed a progressive increase of studies focusing on graphene in the last couple of years. The majority of the works (56%) have been carried out on macrophages, following by lymphocytes (30% of the studies). In the case of lymphocytes, T cells were the most investigated (22%) followed by monocytes and dendritic cells (7%), mixed cell populations (peripheral blood mononuclear cells, 6%), and B and natural killer (NK) cells (1%). Most of the studies focused on toxicity and biocompatibility, while mechanistic insights on the effect of carbon nanotubes on immune cells are generally lacking. Only very recently high-throughput gene-expression analyses have shed new lights on unrecognized effects of carbon nanomaterials on the immune system. These investigations have demonstrated that some f-CNTs can directly elicitate specific inflammatory pathways. The interaction of graphene with the immune system is still at a very early stage of investigation. This comprehensive state of the art on biocompatible f-CNTs and graphene on immune cells provides a useful compass to guide future researches on immunological applications of carbon nanomaterials in medicine.
    Journal of translational medicine. 05/2014; 12(1):138.
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    ABSTRACT: The high versatility of graphene has attracted significant attention in many areas of scientific research from electronics to physics and mechanics. One of the most intriguing utilisation of graphene remains however in nanomedicine and synthetic biology. In particular, the last decade has witnessed an exponential growth in the generation of novel candidate therapeutics of multiple biological activities based on graphene constructs with small molecules, such as anti-cancer drugs. In this Digest, we summarise the different synthetic strategies and routes available to fabricate these promising graphene conjugates and the opportunities for the design of multi-functional tools for synthetic biology that they offer.
    Bioorganic & medicinal chemistry letters 02/2014; · 2.65 Impact Factor
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    ABSTRACT: Carbon nanotubes (CNTs) are promising drug delivery systems due to their external functionalizable surface and their hollowed cavity that can encapsulate several bioactive molecules. In this study, the chemotherapeutic drug cisplatin or an inert platinum(IV) complex were entrapped inside functionalized-multi-walled-CNTs and intravenously injected into mice to investigate the influence of CNTs on the biodistribution of Pt-based molecules. The platinum levels in vital organs suggested that functionalized-CNTs did not affect cisplatin distribution, while they significantly enhanced the accumulation of Pt(IV) sample in some tissues (e.g. in the lungs, suggesting their potential application in lung cancer therapy) and reduced both kidney and liver accumulation (thus decreasing eventual nephrotoxicity, a typical side effect of cisplatin). Concurrently, CNTs did not induce any intrinsic abnormal immune response or inflammation, as confirmed by normal cytokine levels and histological evaluations. Therefore, functionalized nanotubes represent an efficient nano-carrier to improve accumulation of Pt species in targeted tissues/organs.
    Nanomedicine: nanotechnology, biology, and medicine 01/2014; · 6.93 Impact Factor
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    ABSTRACT: Dendrons constituted of an adamantane core, a focal point and three arms, were synthetized starting from a multifunctional adamantane derivative. Maleimido groups at the periphery of the scaffold were used to covalently attach the peptide called P140, a therapeutic phosphopeptide controlling disease activity in systemic lupus, both in mice and patients. Biotinylation of the trimers at the focal point was performed using click chemistry and the conjugates were studied in terms of solubility, binding affinity to its receptor, the HSPA8/HSC70 chaperone protein, effect on HSPA8 folding property and in vivo activity. The results showed that the trimerization of P140 peptide does not trigger aggregation or steric hindrances during the interaction with HSPA8 protein. Compared to the monomeric cognate peptide, the trivalent P140 peptide displayed the same capacity, in vitro, to down-regulate HSPA8 activity and, in vivo in MRL/lpr lupus-prone mice, to reduce abnormal blood hypercellularity. The control trimer synthesized with the same scaffold and a scrambled sequence of P140 showed no effect in vivo. This work reveals that adamantane-based scaffolds with a well-defined spatial conformation are promising trivalent systems for molecular recognition and for biomedical applications.
    Biomaterials 01/2014; 35(26):7553–7561. · 8.31 Impact Factor
  • Maxime Grillaud, Julie Russier, Alberto Bianco
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    ABSTRACT: Dendrons used as synthetic carriers are promising nanostructures for biomedical applications. Some polycationic dendritic systems, like the commercially available PEI (polyethylenimine), have the ability to deliver genetic material into cells. Nevertheless polycationic vectors are often associated with potential cellular toxicity which prevents their use in clinical development. In this context our research focused on the design and the synthesis of a novel type of polycationic dendrons which are able to penetrate into cells without triggering cytotoxic effects. We synthesized 1st and 2nd generation polycationic adamantane-based dendrons via a combined protection/deprotection strategy starting from different adamantane scaffolds. The linker between the adamantane cores is constituted of short ethylene glycol chains and the periphery consists of ammonium and guanidinium groups. None of these dendritic structures which we previously called HYDRAmers displayed significant cytotoxicity effects on two different cell lines (RAW 264.7 and HeLa). Conjugation of the fluorescent probe cyanine 5 at their focal point via click chemistry permitted the evaluation of their cellular internalization. All dendrons penetrated trough the membrane with efficient cellular uptake depending of the dendron generation and the nature of the peripheral groups. These results suggest that the polycationic HYDRAmers are potentially interesting as new vectors in biomedical applications including gene and drug delivery.
    Journal of the American Chemical Society 12/2013; · 10.68 Impact Factor
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    ABSTRACT: Nanomaterials interact with cells and modify their function and biology. Manufacturing this ability can provide tissue-engineering scaffolds with nanostructures able to influence tissue growth and performance. Carbon nanotube compatibility with biomolecules motivated ongoing interest in the development of biosensors and devices including such materials. More recently, carbon nanotubes have been applied in several areas of nerve tissue engineering to study cell behavior or to instruct the growth and organization of neural networks. To gather further knowledge on the true potential of future constructs, in particular to assess their immune-modulatory action, we evaluate carbon nanotubes interactions with human dendritic cells (DCs). DCs are professional antigen-presenting cells and their behavior can predict immune responses triggered by adhesion-dependent signaling. Here, we incorporate DC cultures to carbon nanotubes and we show by phenotype, microscopy and transcriptional analysis that in vitro differentiated and activated DCs show, when interfaced to carbon nanotubes a lower immunogenic profile.
    Nano Letters 11/2013; · 13.03 Impact Factor
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    ABSTRACT: Graphene family nanomaterials are currently being extensively explored for applications in the field of nanotechnology. The unique intrinsic properties treasured in their simple molecular design and their ability to work in coherence with other existing nanomaterials make graphene family nanomaterials the most promising candidates for different types of applications. This review highlights the scope and utility of these multifaceted nanomaterials in nanobiotechnology and biomedicine. In a tandem approach, this review presents the smooth inclusion of these nanomaterials into existing designs for creating efficient working models at the nanoscale level as well as discussing their broad future possibilities.
    Nanomedicine 10/2013; 8(10):1669-88. · 5.26 Impact Factor
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    ABSTRACT: Graphene oxide (GO) is attracting an ever-growing interest in different fields and applications. Not much is known about the possible impact of GO sheet lateral dimensions on their effects in vitro, especially on human primary cells. In an attempt to address this issue, we present a study to evaluate, how highly soluble 2-dimensional GO constituted of large or small flakes affects human monocyte derived macrophages (hMDM). For this purpose, the lateral size of GO was tuned using sonication and three samples were obtained. The non sonicated one presented large flakes (∼1.32 μm) while sonication for 2 and 26 hours generated small (∼0.27 μm) and very small (∼0.13 μm) sheets of GO, respectively. Cell studies were then conducted to evaluate the cytotoxicity, the oxidative stress induction, the activation potential and the pro-inflammatory effects of these different types of GO at increasing concentrations. In comparison, the same experiments were run on murine intraperitoneal macrophages (mIPM). The interaction between GO and cells was further examined by TEM and Raman spectroscopy. Our data revealed that the GO sheet size had a significant impact on different cellular parameters (i.e. cellular viability, ROS generation, and cellular activation). Indeed, the more the lateral dimensions of GO were reduced, the higher were the cellular internalization and the effects on cellular functionality. Our data also revealed a particular interaction of GO flakes with the cellular membrane. In fact, a GO mask due to the parallel arrangement of the graphene sheets on the cellular surface was observed. Considering the mask effect, we have hypothesized that this particular contact between GO sheets and the cell membrane could either promote their internalization or isolate cells from their environment, thus possibly accounting for the following impact on cellular parameters.
    Nanoscale 10/2013; · 6.73 Impact Factor
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    ABSTRACT: Multi-walled carbon nanotubes (MWCNTs) were functionalized with fibroblast growth factor (FGF) and the advantages of their use as scaffolds for bone augmentation were evaluated in vitro and in vivo. The activity of FGF was assessed by measuring the effect on the proliferation of rat bone marrow stromal cells (RBMSCs). The presence of FGF enhanced the proliferation of RBMSCs and the FGF covalently conjugated to the nanotubes (FGF-CNT) showed the same effect as FGF alone. In addition, FGF-CNT coated sponges were implanted between the parietal bone and the periosteum of rats and the formation of new bone was investigated. At day 14 after implantation, a larger amount of newly formed bone was clearly observed in most pores of FGF-CNT coated sponges. These findings indicated that MWCNTs accelerated new bone formation in response to FGF, as well as the integration of particles into new bone during its formation. Scaffolds coated with FGF-CNT could be considered as promising novel substituting materials for bone regeneration in future tissue engineering applications.
    Nanotechnology 09/2013; 24(43):435101. · 3.84 Impact Factor
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    ABSTRACT: Study of the mechanisms understanding how chemically functionalized carbon nanotubes internalize into mammalian cells is important in view of their design as new tools for therapeutic and diagnostic applications. The initial contact between the nanotube and the cell membrane allows elucidation of the types of interaction that are occurring and the contribution from the types of functional groups at the nanotube surface. Here we offer a combination of experimental and theoretical evidence of the initial phases of interaction between functionalized carbon nanotubes with model and cellular membranes. Both experimental and theoretical data reveal the critical parameters to determine direct translocation of the nanotubes through the membrane into the cytoplasm as a result of three distinct processes that can be summarized as landing, piercing and uptake.
    Nanoscale 09/2013; · 6.73 Impact Factor

Publication Stats

6k Citations
1,262.68 Total Impact Points

Institutions

  • 2013–2014
    • The University of Manchester
      • Faculty of Medical and Human Sciences
      Manchester, England, United Kingdom
    • University of Birmingham
      Birmingham, England, United Kingdom
    • Erasmus MC
      Rotterdam, South Holland, Netherlands
    • Guru Nanak Dev University
      Amritsar, Punjab, India
  • 2003–2014
    • Institut de Génétique et de Biologie Moléculaire et Cellulaire
      Strasburg, Alsace, France
  • 2000–2014
    • French National Centre for Scientific Research
      • Institute for Molecular and Cellular Biology (IBMC)
      Lutetia Parisorum, Île-de-France, France
  • 1994–2013
    • Università degli Studi di Trieste
      • Department of Chemical and Pharmaceutical Sciences
      Trieste, Friuli Venezia Giulia, Italy
  • 2012
    • University of Franche-Comté
      • Institut UTINAM
      Besançon, Franche-Comte, France
    • Paris Diderot University
      Lutetia Parisorum, Île-de-France, France
    • University College London
      • Department of Neurodegenerative Disease
      London, ENG, United Kingdom
  • 2011–2012
    • Università degli Studi di Sassari
      • • Dipartimento di Chimica e Farmacia
      • • Dipartimento di Scienze Biomediche
      Sassari, Sardinia, Italy
    • Nagoya University
      • Graduate School of Engineering
      Nagoya-shi, Aichi-ken, Japan
  • 2005–2012
    • University of London
      • The School of Pharmacy
      London, ENG, United Kingdom
  • 1997–2010
    • University of Padova
      • Department of Chemical Sciences
      Padova, Veneto, Italy
  • 1996–2009
    • National Research Council
      • Institute of Biomolecular Chemistry ICB
      Roma, Latium, Italy
  • 2006
    • University of Patras
      • Department of Material Science
      Patrís, Kentriki Makedonia, Greece
  • 2004
    • Vienna University of Technology
      • Institute of Applied Synthetic Chemistry
      Vienna, Vienna, Austria
  • 2001
    • University of Strasbourg
      Strasburg, Alsace, France