Alberto Bianco

Institut de Génétique et de Biologie Moléculaire et Cellulaire, Strasburg, Alsace, France

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Publications (228)1544.35 Total impact

  • Julie Russier, Maxime Grillaud, Alberto Bianco
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    ABSTRACT: Dendrimers and dendrons appeared to potentially fulfill the requirements for being good and well-defined carriers in drug and gene delivery applications. We recently demonstrated that polycationic adamantane-based dendrons called HYDRAmers are easily internalized by both phagocytic and non-phagocytic cells in vitro. The aim of the present study was to investigate which of the different pathways of cellular internalization is involved in the cellular uptake of the first and second generation ammonium and guanidinium HYDRAmers. For this purpose, we have evaluated the internalization of fluorescently labeled-HYDRAmers in both phagocytic murine macrophages and non-phagocytic human cervix epithelioid carcinoma cells in the presence of different well-known active uptake inhibitors. Our data revealed that the first and second generation HYDRAmers are internalized via different endocytic pathways based on the cellular type and on the type of functional groups present at the periphery of the dendrons. In particular, it was registered that the first generations were mainly internalized by clathrin-mediated endocytosis and macropinocytosis while the cellular internalization of the second generations was less affected by the inhibitory conditions of the endocytic pathways. These results suggest the possibility of addressing dendrimers towards specific subcellular compartments by tuning their structure properties and in particular the functional groups at their periphery.
    Bioconjugate Chemistry 06/2015; DOI:10.1021/acs.bioconjchem.5b00270 · 4.82 Impact Factor
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    ABSTRACT: Surface tunability and their ability to translocate plasma membranes make chemically functionalized carbon nanotubes (f-CNTs) promising intracellular delivery systems for therapeutic or diagnostic purposes in the central nervous system (CNS). The present study aimed to determine the biological impact of different types of multi-walled CNTs (MWNTs) on primary neuronal and glial cell populations isolated from foetal rat frontal cortex (FCO) and striatum (ST). Neurons from both brain regions were generally not affected by exposure to MWNTs as determined by a modified LDH assay. In contrast, the viability of mixed glia was reduced in ST-derived mixed glial cultures, but not in FCO-derived ones. Cytotoxicity was independent of MWNT type or dose, suggesting an inherent sensitivity to CNTs. Characterization of the cell populations in mixed glial cultures prior to nanotube exposure showed higher number of CD11b/c positive cells in the ST-derived mixed glial cultures. After exposure to MWNTs, CNT were uptaken more effectively by CD11b/c positive cells (microglia), compared to GFAP positive cells (astrocytes). When exposed to conditioned media from microglia enriched cultures exposed to MWNTs, ST-derived glial cultures secreted more NO than FCO-derived cells. These results suggested that the more significant cytotoxic response obtained from ST-derived mixed glia cultures was related to the higher number of microglial cells in this brain region. Our findings emphasize the role that resident macrophages of the CNS play in response to nanomaterials and the need to thoroughly investigate the brain region-specific effects towards designing implantable devices or delivery systems to the CNS.
    ACS Nano 06/2015; DOI:10.1021/acsnano.5b02358 · 12.03 Impact Factor
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    ABSTRACT: Polo-Like Kinase (PLK1) has been identified as a potential target in cancer gene therapy via chemical or genetic inhibitory approaches. The biomedical applications of chemically functionalized carbon nanotubes (f-CNTs) in cancer therapy have been studied due to their ability to efficiently deliver siRNA intracellularly. In this study, we established the capacity of cationic MWNT-NH3+ to deliver the apoptotic siRNA against PLK1 (siPLK1) in Calu6 tumor xenografts by direct intratumoural injections. A direct comparison with cationic liposomes was made. This study validates the PLK1 gene as a potential target in cancer gene therapy including lung cancer, as demonstrated by the therapeutic efficacy of siPLK1:MWNT-NH3+ complexes and their ability to significantly improve animal survival. Biological analysis of the siPLK1:MWNT-NH3+ treated tumors by RT-PCR and Western blot, in addition to TUNEL staining confirmed the biological functionality of the siRNA intratumourally, suggesting that tumor eradication was due to PLK1 knockdown. Furthermore, by using a fluorescently labelled, non-coding siRNA sequence complexed with MWNT-NH3+, we established for the first time that the improved therapeutic efficacy observed in f-CNT-based siRNA delivery is directly proportional to the enhanced siRNA retention in the solid tumor and subsequent uptake by tumor cells after local administration in vivo.
    Bioconjugate Chemistry 06/2015; DOI:10.1021/acs.bioconjchem.5b00249 · 4.82 Impact Factor
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    ABSTRACT: Understanding human health risk associated with the rapidly emerging graphene-based nanomaterials represents a great challenge because of the diversity of applications and the wide range of possible ways of exposure to this type of materials. Herein, the biodegradation of graphene oxide (GO) sheets is reported by using myeloperoxidase (hMPO) derived from human neutrophils in the presence of a low concentration of hydrogen peroxide. The degradation capability of the enzyme on three different GO samples containing different degree of oxidation on their graphenic lattice, leading to a variable dispersibility in aqueous media is compared. hMPO fails in degrading the most aggregated GO, but succeeds to completely metabolize highly dispersed GO samples. The spectroscopy and microscopy analyses provide unambiguous evidence for the key roles played by hydrophilicity, negative surface charge, and colloidal stability of the aqueous GO in their biodegradation by hMPO catalysis. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
    Small 05/2015; DOI:10.1002/smll.201500038 · 7.51 Impact Factor
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    ABSTRACT: Design of graphene-based materials for biomedical purposes is of great interest. Graphene oxide (GO) represents the most widespread type of graphene material in biological studies. In this work, thin GO sheets were further chemically functionalized with DOTA (1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid), a stable radiometal chelating agent, by an epoxide opening reaction. We report the tissue distribution of the functionalized GO sheets labeled with radioactive indium (111In) after intravenous administration in mice. Whole body single photon emission computed tomography (SPECT/CT) imaging, gamma counting studies, Raman microscopy and histological investigations indicated extensive urinary excretion and predominant spleen accumulation. Intact GO sheets were detected in the urine of injected mice by Raman spectroscopy, high resolution transmission electron microscopy (HR-TEM) and electron diffraction. These results offer a previously unavailable pharmacological understanding on how chemically functionalized GO sheets transport in the blood stream and interact with physiological barriers that will determine their body excretion and tissue accumulation.
    Chemical Science 04/2015; DOI:10.1039/C5SC00114E · 8.60 Impact Factor
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    ABSTRACT: The use of platinum-based chemotherapeutic drugs in cancer therapy still suffers from severe disadvantages, such as lack of appropriate selectivity for tumor tissues and insurgence of multi-drug resistance. Moreover, drug efficacy can be attenuated by several mechanisms such as premature drug inactivation, reduced drug uptake inside cells and increased drug efflux once internalized. The use of functionalized carbon nanotubes (CNTs) as chemotherapeutic drug delivery systems is a promising strategy to overcome such limitations due to their ability to enhance cellular internalization of poorly permeable drugs and thus increase the drug bioavailability at the diseased site, compared to the free drug. Furthermore, the possibility to encapsulate agents in the nanotubes' inner cavity can protect the drug from early inactivation and their external functionalizable surface is useful for selective targeting. In this study, a hydrophobic platinum(iv) complex was encapsulated within the inner space of two different diameter functionalized multi-walled CNTs (Pt(iv)@CNTs). The behavior of the complexes, compared to the free drug, was investigated on both HeLa human cancer cells and RAW 264.7 murine macrophages. Both CNT samples efficiently induced cell death in HeLa cancer cells 72 hours after the end of exposure to CNTs. Although the larger diameter CNTs were more cytotoxic on HeLa cells compared to both the free drug and the smaller diameter nanotubes, the latter allowed a prolonged release of the encapsulated drug, thus increasing its anticancer efficacy. In contrast, both Pt(iv)@CNT constructs were poorly cytotoxic on macrophages and induced negligible cell activation and no pro-inflammatory cytokine production. Both CNT samples were efficiently internalized by the two types of cells, as demonstrated by transmission electron microscopy observations and flow cytometry analysis. Finally, the platinum levels found in the cells after Pt(iv)@CNT exposure demonstrate that they can promote drug accumulation inside cells in comparison with treatment with the free complex. To conclude, our study shows that CNTs are promising nanocarriers to improve the accumulation of a chemotherapeutic drug and its slow release inside tumor cells, by tuning the CNT diameter, without inducing a high inflammatory response.
    Nanoscale 03/2015; 7(12). DOI:10.1039/c5nr00220f · 6.74 Impact Factor
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  • Theranostics 01/2015; 5(7):710-723. DOI:10.7150/thno.11387 · 7.83 Impact Factor
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    ABSTRACT: Multifunctional carbon nanohorn (CNH) complexes were synthesized using oxidized CNH, magnetite (MAG) nanoparticles, and polyethyleneimine (PEI). The ferromagnetic MAG nanoparticles were loaded onto CNH (MAG-CNH) using iron(II) acetate and subsequent heat treatment. Chemical functionalization of the MAG-CNH complexes with PEI improved their water-dispersibility and allowed further conjugation with a fluorophore. The application of an external magnetic field significantly intensified the targeted vectorization of CNH complexes into human cervical cancer (HeLa) cells. Following cell uptake, laser irradiation of the cells showed a significant enhancement in the photothermal effects of CNHs leading to cell death. We have confirmed that the photothermal properties and ferromagnetic characteristics of CNH complexes show efficient cell elimination. The present study is an essential step toward the development of an innovative cancer therapy and a highly sensitive detection of cancer cells at the single-cell level.
    Chemistry - An Asian Journal 01/2015; 10(1). DOI:10.1002/asia.201403059 · 3.94 Impact Factor
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    Maxime Grillaud, Alberto Bianco
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    ABSTRACT: The remarkable structural and chemical properties of adamantane afford attractive opportunities to design various adamantane-based scaffolds for biomedical applications. A wide range of mono-functionalized adamantane compounds have already been investigated and reviewed, mostly as anti-viral agents. The four bridgehead positions of adamantane provide many possibilities to design poly-functional derivatives, and the recent conception of adamantane building blocks with multiple substituents has shown promising applications in several domains. In this review, we provide a detailed description of the different ways to synthesize multifunctional derivatives starting from adamantane molecule as the main core. We will then describe the interesting biological activity of the diverse multivalent scaffolds, focusing in particular on peptide-based systems. The results reported here will certainly encourage the development of novel adamantane-based structures for biological purposes. Copyright © 2014 European Peptide Society and John Wiley & Sons, Ltd. Copyright © 2014 European Peptide Society and John Wiley & Sons, Ltd.
    Journal of Peptide Science 12/2014; 21(5). DOI:10.1002/psc.2719 · 1.86 Impact Factor
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    ABSTRACT: Nanocomposites combining multiple functionalities in one single nanoobject hold a lot of promises for biomedical applications. In this work carbon nanotubes (CNTs) were filled with ferrite nanoparticles (NPs) to develop the magnetic manipulation of the nanotubes and their theranostic applications. The challenges were both the filling of CNTs with a high amount of magnetic NPs and their functionalization to form biocompatible water suspensions. We are here proposing a filling process using CNTs as nanoreactors for high yield in situ growth of ferrite NPs into the inner carbon cavity. At first, NPs were formed inside the nanotubes by thermal decomposition of an iron stearate precursor. A second filling step was then performed with iron or cobalt stearate precursors to enhance the encapsulation yield and block the formed NPs inside the tubes. Water suspensions were then obtained by addition of amino groups via the covalent functionalization of the external surface of the nanotubes. Microstructural and magnetic characterizations confirmed the confinement of NPs into the anisotropic structure of CNTs making them suitable for magnetic manipulations and MRI detection. Interactions of highly water dispersible CNTs with tumor cells could be modulated by magnetic fields without toxicity, allowing to control their orientation within the cell and to induce submicron magnetic stirring. The magnetic properties were also used to quantify CNTs cellular uptake by measuring the cell magnetophoretic mobility. Finally, the photothermal ablation of tumor cells could be enhanced by magnetic stimulus, harnessing the hybrid properties of NP loaded-CNTs.
    ACS Nano 10/2014; DOI:10.1021/nn5040923 · 12.03 Impact Factor
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    ABSTRACT: A single organism comprises diverse types of cells. To acquire a detailed understanding of the biological functions of each cell, comprehensive control and analysis of homeostatic processes at the single-cell level are required. In this study, we develop a new type of light-driven nanomodulator comprising dye-functionalized carbon nanohorns (CNHs) that generate heat and reactive oxygen species under biologically transparent near-infrared (NIR) laser irradiation. By exploiting the physicochemical properties of the nanohorns, cellular calcium ion flux and membrane currents were successfully controlled at the single-cell level. In addition, the nanomodulator allows a remote bioexcitation of tissues during NIR laser exposure making this system a powerful tool for single-cell analyses and innovative cell therapies.
    Angewandte Chemie International Edition 10/2014; DOI:10.1002/anie.201407169 · 11.34 Impact Factor
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    ABSTRACT: Among targeted delivery systems, platforms with nanosize dimensions, such as carbon nanomaterials (CNMs) and metal nanoparticles (NPs), have shown great potential in biomedical applications. They have received considerable interest in recent years, especially with respect to their potential utilization in the field of cancer diagnosis and therapy. The multifunctionalization of nanomaterials provides opportunities to use them as multimodal agents for theranostics, a combination of therapy and diagnosis. Carbon nanotubes and graphene are within the most widely used CNMs because of their unique structural and physico-chemical properties. Their high specific surface area allows an efficient drug loading and the possibility of functionalization with various bioactive molecules. In addition, CNMs are ideal platforms for the attachment of NPs. In the biomedical field, NPs have also shown tremendous promises in drug delivery, non-invasive tumor imaging and early detection due to their optical and magnetic properties. NP/CNM hybrids not only combine the unique properties of the NPs and CNMs, but they also exhibit new properties arising from the interactions between the two entities. In this review, the preparation of CNMs conjugated to different types of metal NPs and their applications in diagnosis, imaging, therapy, and theranostics are presented.
    British Journal of Pharmacology 10/2014; DOI:10.1111/bph.12984 · 4.99 Impact Factor
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    ABSTRACT: We present the science and technology roadmap (STR) for graphene, related two-dimensional (2d) crystals, and hybrid systems, targeting an evolution in technology, with impacts and benefits reaching into most areas of society. The roadmap was developed within the framework of the European Graphene Flagship and outlines the main targets and research areas as best understood at the start of this ambitious project. In this document we provide an overview of the key aspects of graphene and related materials (GRMs), ranging from fundamental research challenges to a variety of applications in a large number of sectors, highlithing the roadmap to take GRMs from a state of raw potential to a point where they might revolutionize multiple industries: from flexible, wearable and transparent electronics to high performance computing and spintronics.
    Nanoscale 09/2014; 7(11). DOI:10.1039/C4NR01600A · 6.74 Impact Factor
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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; 24(45). DOI:10.1002/adfm.201402234 · 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; 35(35). DOI:10.1016/j.biomaterials.2014.07.054 · 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; 18(1). DOI:10.1016/j.mattod.2014.07.009 · 10.85 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 08/2014; 35(26):7553–7561. DOI:10.1016/j.biomaterials.2014.05.017 · 8.31 Impact Factor
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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 07/2014; 53(30). DOI:10.1002/anie.201403335 · 13.45 Impact Factor
  • Angewandte Chemie 07/2014; 126(30). DOI:10.1002/ange.201403335

Publication Stats

13k Citations
1,544.35 Total Impact Points

Institutions

  • 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
  • 1996–2014
    • Università degli Studi di Trieste
      • Department of Chemical and Pharmaceutical Sciences
      Trst, Friuli Venezia Giulia, Italy
  • 2009–2010
    • University of London
      • The School of Pharmacy
      Londinium, England, United Kingdom
    • The School of Pharmacy
      • School of Pharmacy
      Londinium, England, United Kingdom
  • 1993–2010
    • University of Padova
      • Department of Chemical Sciences
      Padua, Veneto, Italy
  • 2006
    • University of Patras
      • Department of Material Science
      Rhion, West Greece, Greece
  • 2002
    • French Institute of Health and Medical Research
      Lutetia Parisorum, Île-de-France, France
  • 2000–2001
    • University of Strasbourg
      Strasburg, Alsace, France
  • 1998
    • Lodz University of Technology
      • Institute of Organic Chemistry
      Łódź, Łódź Voivodeship, Poland