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2014
Servant A, Bianco A, Prato M, Kostarelos K
Graphene for multi-functional synthetic biology: the last 'zeitgeist' in nanomedicine Journal Article
In: Bioorganic & Medicinal Chemistry Letters, vol. 24, no. 7, pp. 1638–1649, 2014, ISSN: 1464-3405.
Abstract | Links | BibTeX | Tags: Antineoplastic Agents, carbon, Drug delivery, Drug Design, Graphite, I2CT, Nanomaterials, Nanomedicine, nanotechnology, Synthetic Biology, Team-Bianco
@article{servant_graphene_2014,
title = {Graphene for multi-functional synthetic biology: the last 'zeitgeist' in nanomedicine},
author = {A Servant and A Bianco and M Prato and K Kostarelos},
doi = {10.1016/j.bmcl.2014.01.051},
issn = {1464-3405},
year = {2014},
date = {2014-01-01},
journal = {Bioorganic & Medicinal Chemistry Letters},
volume = {24},
number = {7},
pages = {1638--1649},
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.},
keywords = {Antineoplastic Agents, carbon, Drug delivery, Drug Design, Graphite, I2CT, Nanomaterials, Nanomedicine, nanotechnology, Synthetic Biology, Team-Bianco},
pubstate = {published},
tppubtype = {article}
}
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.
2011
Lamanna Giuseppe, Russier Julie, Ménard-Moyon Cécilia, Bianco Alberto
HYDRAmers: design, synthesis and characterization of different generation novel Hydra-like dendrons based on multifunctionalized adamantane Journal Article
In: Chemical Communications (Cambridge, England), vol. 47, no. 31, pp. 8955–8957, 2011, ISSN: 1364-548X.
Abstract | Links | BibTeX | Tags: Adamantane, Animals, Cell Line, Dendrimers, Drug Design, Humans, I2CT, L-Lactate Dehydrogenase, Magnetic Resonance Spectroscopy, Mice, Team-Bianco, tumor
@article{lamanna_hydramers_2011,
title = {HYDRAmers: design, synthesis and characterization of different generation novel Hydra-like dendrons based on multifunctionalized adamantane},
author = {Giuseppe Lamanna and Julie Russier and Cécilia Ménard-Moyon and Alberto Bianco},
doi = {10.1039/c1cc11689d},
issn = {1364-548X},
year = {2011},
date = {2011-08-01},
journal = {Chemical Communications (Cambridge, England)},
volume = {47},
number = {31},
pages = {8955--8957},
abstract = {In this communication we present a new synthetic strategy to different generation Hydra-like dendrons based on tetrafunctionalized adamantane as a building block. The novel dendrons, which we termed HYDRAmers, possess at the periphery and at the central core orthogonal protections that can be exploited for conjugation of targeting ligands, drugs and/or imaging probes.},
keywords = {Adamantane, Animals, Cell Line, Dendrimers, Drug Design, Humans, I2CT, L-Lactate Dehydrogenase, Magnetic Resonance Spectroscopy, Mice, Team-Bianco, tumor},
pubstate = {published},
tppubtype = {article}
}
In this communication we present a new synthetic strategy to different generation Hydra-like dendrons based on tetrafunctionalized adamantane as a building block. The novel dendrons, which we termed HYDRAmers, possess at the periphery and at the central core orthogonal protections that can be exploited for conjugation of targeting ligands, drugs and/or imaging probes.
Limmer Stefanie, Quintin Jessica, Hetru Charles, Ferrandon Dominique
Virulence on the fly: Drosophila melanogaster as a model genetic organism to decipher host-pathogen interactions Journal Article
In: Curr Drug Targets, vol. 12, no. 7, pp. 978–999, 2011, ISSN: 1873-5592.
Abstract | BibTeX | Tags: Animal, Animals, Anti-Infective Agents, Disease Models, Drug Delivery Systems, Drug Design, Drug Resistance, ferrandon, Fungi, High-Throughput Screening Assays, Host-Pathogen Interactions, Humans, M3i, Microbial, Pseudomonas aeruginosa
@article{limmer_virulence_2011b,
title = {Virulence on the fly: Drosophila melanogaster as a model genetic organism to decipher host-pathogen interactions},
author = {Stefanie Limmer and Jessica Quintin and Charles Hetru and Dominique Ferrandon},
issn = {1873-5592},
year = {2011},
date = {2011-06-01},
journal = {Curr Drug Targets},
volume = {12},
number = {7},
pages = {978--999},
abstract = {To gain an in-depth grasp of infectious processes one has to know the specific interactions between the virulence factors of the pathogen and the host defense mechanisms. A thorough understanding is crucial for identifying potential new drug targets and designing drugs against which the pathogens might not develop resistance easily. Model organisms are a useful tool for this endeavor, thanks to the power of their genetics. Drosophila melanogaster is widely used to study host-pathogen interactions. Its basal immune response is well understood and is briefly reviewed here. Considerations relevant to choosing an adequate infection model are discussed. This review then focuses mainly on infections with two categories of pathogens, the well-studied Gram-negative bacterium Pseudomonas aeruginosa and infections by fungi of medical interest. These examples provide an overview over the current knowledge on Drosophila-pathogen interactions and illustrate the approaches that can be used to study those interactions. We also discuss the usefulness and limits of Drosophila infection models for studying specific host-pathogen interactions and high-throughput drug screening.},
keywords = {Animal, Animals, Anti-Infective Agents, Disease Models, Drug Delivery Systems, Drug Design, Drug Resistance, ferrandon, Fungi, High-Throughput Screening Assays, Host-Pathogen Interactions, Humans, M3i, Microbial, Pseudomonas aeruginosa},
pubstate = {published},
tppubtype = {article}
}
To gain an in-depth grasp of infectious processes one has to know the specific interactions between the virulence factors of the pathogen and the host defense mechanisms. A thorough understanding is crucial for identifying potential new drug targets and designing drugs against which the pathogens might not develop resistance easily. Model organisms are a useful tool for this endeavor, thanks to the power of their genetics. Drosophila melanogaster is widely used to study host-pathogen interactions. Its basal immune response is well understood and is briefly reviewed here. Considerations relevant to choosing an adequate infection model are discussed. This review then focuses mainly on infections with two categories of pathogens, the well-studied Gram-negative bacterium Pseudomonas aeruginosa and infections by fungi of medical interest. These examples provide an overview over the current knowledge on Drosophila-pathogen interactions and illustrate the approaches that can be used to study those interactions. We also discuss the usefulness and limits of Drosophila infection models for studying specific host-pathogen interactions and high-throughput drug screening.
Benincasa Monica, Pacor Sabrina, Wu Wei, Prato Maurizio, Bianco Alberto, Gennaro Renato
Antifungal activity of amphotericin B conjugated to carbon nanotubes Journal Article
In: ACS nano, vol. 5, no. 1, pp. 199–208, 2011, ISSN: 1936-086X.
Abstract | Links | BibTeX | Tags: Amphotericin B, Antifungal Agents, Candida, carbon, Cell Membrane, Deoxycholic Acid, Drug Design, Drug Resistance, Fungal, Humans, I2CT, Jurkat Cells, Kinetics, Membrane Potentials, Nanotubes, Team-Bianco
@article{benincasa_antifungal_2011,
title = {Antifungal activity of amphotericin B conjugated to carbon nanotubes},
author = {Monica Benincasa and Sabrina Pacor and Wei Wu and Maurizio Prato and Alberto Bianco and Renato Gennaro},
doi = {10.1021/nn1023522},
issn = {1936-086X},
year = {2011},
date = {2011-01-01},
journal = {ACS nano},
volume = {5},
number = {1},
pages = {199--208},
abstract = {Amphotericin B (AMB) has long been considered the most effective drug in the treatment of serious invasive fungal infections. There are, however, major limitations to its use, due to several adverse effects, including acute infusional reactions and, most relevant, a dose-dependent nephrotoxicity. At least some of these effects are attributed to the aggregation of AMB as a result of its poor water solubility. To overcome this problem, reformulated versions of the drug have been developed, including a micellar dispersion of AMB with sodium deoxycholate (AMBD), its encapsulation into liposomes, or its incorporation into lipidic complexes. The development of nanobiotechnologies provides novel potential drug delivery systems that make use of nanomaterials such as functionalized carbon nanotubes (f-CNTs), which are emerging as an innovative and efficient tool for the transport and cellular translocation of therapeutic molecules. In this study, we prepared two conjugates between f-CNTs and AMB. The antifungal activity of these conjugates was tested against a collection of reference and clinical fungal strains, in comparison to that of AMB alone or AMBD. Measured minimum inhibition concentration (MIC) values for f-CNT-AMB conjugates were either comparable to or better than those displayed by AMB and AMBD. Furthermore, AMBD-resistant Candida strains were found to be susceptible to f-CNT-AMB 1. Additional studies, aimed at understanding the mechanism of action of the conjugates, suggest a nonlytic mechanism, since the compounds show a major permeabilizing effect on the tested fungal strains only after extended incubation. Interestingly, the f-CNT-AMB 1 does not show any significant toxic effect on Jurkat cells at antifungal concentrations.},
keywords = {Amphotericin B, Antifungal Agents, Candida, carbon, Cell Membrane, Deoxycholic Acid, Drug Design, Drug Resistance, Fungal, Humans, I2CT, Jurkat Cells, Kinetics, Membrane Potentials, Nanotubes, Team-Bianco},
pubstate = {published},
tppubtype = {article}
}
Amphotericin B (AMB) has long been considered the most effective drug in the treatment of serious invasive fungal infections. There are, however, major limitations to its use, due to several adverse effects, including acute infusional reactions and, most relevant, a dose-dependent nephrotoxicity. At least some of these effects are attributed to the aggregation of AMB as a result of its poor water solubility. To overcome this problem, reformulated versions of the drug have been developed, including a micellar dispersion of AMB with sodium deoxycholate (AMBD), its encapsulation into liposomes, or its incorporation into lipidic complexes. The development of nanobiotechnologies provides novel potential drug delivery systems that make use of nanomaterials such as functionalized carbon nanotubes (f-CNTs), which are emerging as an innovative and efficient tool for the transport and cellular translocation of therapeutic molecules. In this study, we prepared two conjugates between f-CNTs and AMB. The antifungal activity of these conjugates was tested against a collection of reference and clinical fungal strains, in comparison to that of AMB alone or AMBD. Measured minimum inhibition concentration (MIC) values for f-CNT-AMB conjugates were either comparable to or better than those displayed by AMB and AMBD. Furthermore, AMBD-resistant Candida strains were found to be susceptible to f-CNT-AMB 1. Additional studies, aimed at understanding the mechanism of action of the conjugates, suggest a nonlytic mechanism, since the compounds show a major permeabilizing effect on the tested fungal strains only after extended incubation. Interestingly, the f-CNT-AMB 1 does not show any significant toxic effect on Jurkat cells at antifungal concentrations.
2008
Geotti-Bianchini Piero, Beyrath Julien, Chaloin Olivier, Formaggio Fernando, Bianco Alberto
Design and synthesis of intrinsically cell-penetrating nucleopeptides Journal Article
In: Organic & Biomolecular Chemistry, vol. 6, no. 20, pp. 3661–3663, 2008, ISSN: 1477-0539.
Abstract | Links | BibTeX | Tags: Amino Acid Sequence, Cell Line, Cells, Drug Design, Humans, I2CT, Molecular Sequence Data, Peptides, Purines, Pyrimidines, Team-Bianco
@article{geotti-bianchini_design_2008,
title = {Design and synthesis of intrinsically cell-penetrating nucleopeptides},
author = {Piero Geotti-Bianchini and Julien Beyrath and Olivier Chaloin and Fernando Formaggio and Alberto Bianco},
doi = {10.1039/b811639c},
issn = {1477-0539},
year = {2008},
date = {2008-10-01},
journal = {Organic & Biomolecular Chemistry},
volume = {6},
number = {20},
pages = {3661--3663},
abstract = {Nucleopeptides, which are constituted of alpha-amino acids bearing nucleobases at their side chains, are able to penetrate into cells and to reach the nucleus without cytotoxic effects.},
keywords = {Amino Acid Sequence, Cell Line, Cells, Drug Design, Humans, I2CT, Molecular Sequence Data, Peptides, Purines, Pyrimidines, Team-Bianco},
pubstate = {published},
tppubtype = {article}
}
Nucleopeptides, which are constituted of alpha-amino acids bearing nucleobases at their side chains, are able to penetrate into cells and to reach the nucleus without cytotoxic effects.
Prato Maurizio, Kostarelos Kostas, Bianco Alberto
Functionalized carbon nanotubes in drug design and discovery Journal Article
In: Accounts of Chemical Research, vol. 41, no. 1, pp. 60–68, 2008, ISSN: 1520-4898.
Abstract | Links | BibTeX | Tags: Animals, carbon, Communicable Diseases, Drug Carriers, Drug Design, Genetic Therapy, Humans, I2CT, Immunization, Nanotubes, Neoplasms, Team-Bianco
@article{prato_functionalized_2008,
title = {Functionalized carbon nanotubes in drug design and discovery},
author = {Maurizio Prato and Kostas Kostarelos and Alberto Bianco},
doi = {10.1021/ar700089b},
issn = {1520-4898},
year = {2008},
date = {2008-01-01},
journal = {Accounts of Chemical Research},
volume = {41},
number = {1},
pages = {60--68},
abstract = {Carbon nanotubes (CNTs) have been proposed and actively explored as multipurpose innovative carriers for drug delivery and diagnostic applications. Their versatile physicochemical features enable the covalent and noncovalent introduction of several pharmaceutically relevant entities and allow for rational design of novel candidate nanoscale constructs for drug development. CNTs can be functionalized with different functional groups to carry simultaneously several moieties for targeting, imaging, and therapy. Among the most interesting examples of such multimodal CNT constructs described in this Account is one carrying a fluorescein probe together with the antifungal drug amphotericin B or fluorescein and the antitumor agent methotrexate. The biological action of the drug in these cases is retained or, as in the case of amphotericin B constructs, enhanced, while CNTs are able to reduce the unwanted toxicity of the drug administered alone. Ammonium-functionalized CNTs can also be considered very promising vectors for gene-encoding nucleic acids. Indeed, we have formed stable complexes between cationic CNTs and plasmid DNA and demonstrated the enhancement of the gene therapeutic capacity in comparison to DNA alone. On the other hand, CNTs conjugated with antigenic peptides can be developed as a new and effective system for synthetic vaccine applications. What makes CNTs quite unique is their ability, first shown by our groups in 2004, to passively cross membranes of many different types of cells following a translocation mechanism that has been termed the nanoneedle mechanism. In that way, CNTs open innumerable possibilities for future drug discovery based on intracellular targets that have been hard to reach until today. Moreover, adequately functionalized CNTs as those shown in this Account can be rapidly eliminated from the body following systemic administration offering further encouragment for their development. CNT excretion rates and accumulation in organs and any reactivity with the immune system will determine the CNT safety profile and, consequently, any further pharmaceutical development. Caution is advised about the need for systematic data on the long-term fate of these very interesting and versatile nano-objects in correlation with the type of CNT material used. CNTs are gradually plyaing a bigger and more important role in the emerging field of nanomedicine; however, we need to guarantee that the great opportunities they offer will be translated into feasible and safe constructs to be included in drug discovery and development pipelines.},
keywords = {Animals, carbon, Communicable Diseases, Drug Carriers, Drug Design, Genetic Therapy, Humans, I2CT, Immunization, Nanotubes, Neoplasms, Team-Bianco},
pubstate = {published},
tppubtype = {article}
}
Carbon nanotubes (CNTs) have been proposed and actively explored as multipurpose innovative carriers for drug delivery and diagnostic applications. Their versatile physicochemical features enable the covalent and noncovalent introduction of several pharmaceutically relevant entities and allow for rational design of novel candidate nanoscale constructs for drug development. CNTs can be functionalized with different functional groups to carry simultaneously several moieties for targeting, imaging, and therapy. Among the most interesting examples of such multimodal CNT constructs described in this Account is one carrying a fluorescein probe together with the antifungal drug amphotericin B or fluorescein and the antitumor agent methotrexate. The biological action of the drug in these cases is retained or, as in the case of amphotericin B constructs, enhanced, while CNTs are able to reduce the unwanted toxicity of the drug administered alone. Ammonium-functionalized CNTs can also be considered very promising vectors for gene-encoding nucleic acids. Indeed, we have formed stable complexes between cationic CNTs and plasmid DNA and demonstrated the enhancement of the gene therapeutic capacity in comparison to DNA alone. On the other hand, CNTs conjugated with antigenic peptides can be developed as a new and effective system for synthetic vaccine applications. What makes CNTs quite unique is their ability, first shown by our groups in 2004, to passively cross membranes of many different types of cells following a translocation mechanism that has been termed the nanoneedle mechanism. In that way, CNTs open innumerable possibilities for future drug discovery based on intracellular targets that have been hard to reach until today. Moreover, adequately functionalized CNTs as those shown in this Account can be rapidly eliminated from the body following systemic administration offering further encouragment for their development. CNT excretion rates and accumulation in organs and any reactivity with the immune system will determine the CNT safety profile and, consequently, any further pharmaceutical development. Caution is advised about the need for systematic data on the long-term fate of these very interesting and versatile nano-objects in correlation with the type of CNT material used. CNTs are gradually plyaing a bigger and more important role in the emerging field of nanomedicine; however, we need to guarantee that the great opportunities they offer will be translated into feasible and safe constructs to be included in drug discovery and development pipelines.
2006
Pastorin Giorgia, Marchesan Silvia, Hoebeke Johan, Ros Tatiana Da, Ehret-Sabatier Laurence, Briand Jean-Paul, Prato Maurizio, Bianco Alberto
Design and activity of cationic fullerene derivatives as inhibitors of acetylcholinesterase Journal Article
In: Organic & Biomolecular Chemistry, vol. 4, no. 13, pp. 2556–2562, 2006, ISSN: 1477-0520.
Abstract | Links | BibTeX | Tags: Acetylcholinesterase, Binding Sites, Cations, Cholinesterase Inhibitors, Drug Design, Fullerenes, I2CT, Models, Molecular, Team-Bianco
@article{pastorin_design_2006,
title = {Design and activity of cationic fullerene derivatives as inhibitors of acetylcholinesterase},
author = {Giorgia Pastorin and Silvia Marchesan and Johan Hoebeke and Tatiana Da Ros and Laurence Ehret-Sabatier and Jean-Paul Briand and Maurizio Prato and Alberto Bianco},
doi = {10.1039/b604361e},
issn = {1477-0520},
year = {2006},
date = {2006-07-01},
journal = {Organic & Biomolecular Chemistry},
volume = {4},
number = {13},
pages = {2556--2562},
abstract = {Four different regioisomers of cationic bis-N,N-dimethylfulleropyrrolidinium salts have been prepared and evaluated as inhibitors of the enzymatic activity of acetylcholinesterase. These fullerene-based derivatives were found to be noncompetitive inhibitors of acetylthiocholine hydrolysis. Molecular modelling was used to describe the possible interactions between the fullerene cage and the amino acids surrounding the cavity of the enzyme. The cationic C(60) derivatives used in this study represent a new class of molecules potentially able to modulate the enzymatic activity of acetylcholinesterase.},
keywords = {Acetylcholinesterase, Binding Sites, Cations, Cholinesterase Inhibitors, Drug Design, Fullerenes, I2CT, Models, Molecular, Team-Bianco},
pubstate = {published},
tppubtype = {article}
}
Four different regioisomers of cationic bis-N,N-dimethylfulleropyrrolidinium salts have been prepared and evaluated as inhibitors of the enzymatic activity of acetylcholinesterase. These fullerene-based derivatives were found to be noncompetitive inhibitors of acetylthiocholine hydrolysis. Molecular modelling was used to describe the possible interactions between the fullerene cage and the amino acids surrounding the cavity of the enzyme. The cationic C(60) derivatives used in this study represent a new class of molecules potentially able to modulate the enzymatic activity of acetylcholinesterase.