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Biomedical subjects

Alberto Bianco

Publications and source records attributed to Alberto Bianco.

At least 19 recordsLinked to original sources

Degradation of a graphene-reinforced polyamide by fungi: When culture conditions matter.

The large-scale production, marketing and disposal of polymer-based graphene products can lead to the dispersal of graphene-enriched plastic particles into terrestrial ecosystems, where they might accumulate if not degraded by organisms. The objective of this work is to test the degradability and compatibility of one polyamide-6 polymer reinforced with reduced graphene-oxide (PA6-rGO) and its base constituents (polyamide-6, PA6; reduced graphene oxide, rGO) using mono- and co-cultures of two lignin-degrading fungi (Bjerkandera adusta and Morchella esculenta) grown under different nutrient conditions. Fungal (co-)cultures were exposed to pure rGO or abraded powders of PA6 and PA6-rGO in two different liquid media, and monitored over time for biomass growth, H2O2 production, and activity of two lignolytic enzymes (i.e., Laccase, Lac, and Lignin peroxidase, LiP). The changes in polyamide structure were evaluated by proton nuclear magnetic resonance and mass spectrometry, and changes in rGO were evaluated by Raman spectroscopy. The materials had no effect on fungal growth. PA6 increased Lac secretion only in low nutrient medium, while PA6-rGO slightly suppressed LiP activity. Only M. esculenta promoted polyamides oxidation when cultured in a low nutrient medium, as evidenced by a change in mass distribution values (m/z: 400-420) and the appearance of a new resonance peak (at 5.37 ppm). Lignolytic exudates in co-cultures low in nutrients caused a greater change in rGO, as shown by the increase in the ID/IG ratio. The degradation of rGO, PA6 and PA6-rGO depended on culture conditions.

Graphite↗

Carbon nanotubes as nanomedicines: from toxicology to pharmacology.

Various biomedical applications of carbon nanotubes have been proposed in the last few years leading to the emergence of a new field in diagnostics and therapeutics. Most of these applications will involve the administration or implantation of carbon nanotubes and their matrices into patients. The toxicological and pharmacological profile of such carbon nanotube systems developed as nanomedicines will have to be determined prior to any clinical studies undertaken. This review brings together all the toxicological and pharmacological in vivo studies that have been carried out using carbon nanotubes, to offer the first summary of the state-of-the-art in the pharmaceutical development of carbon nanotubes on the road to becoming viable and effective nanomedicines.

Animals↗

Design and activity of cationic fullerene derivatives as inhibitors of acetylcholinesterase.

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.

Acetylcholinesterase↗

Solid-phase synthesis of CD40L mimetics.

The C3-symmetric molecule has been previously shown to mimic CD40 ligand (CD40L) homotrimers and to display effector functions. This molecule consists of a cyclic hexapeptide core containing the repetition of the D-Ala-L-Lys motif. The side chains of the lysine residues have been modified by appending the CD40L-derived sequence 143Lys-Gly-Tyr-Tyr146 via a 6-aminohexanoic acid residue as a spacer. The present report describes a general solid-phase synthesis approach to and related trimeric architectures. In addition, their CD40 binding properties as well as their effector functions have been evaluated.

Apoptosis↗

[60]fullerene-pyrrolidine-N-oxides.

Eight members of a new family of fullerene derivatives, [60]fulleropyrrolidine-N-oxides, have been synthesized and characterized. Facile oxidation, by a peracid, of the parent [60]fulleropyrrolidine gave clean conversions into the product molecules, in which the tertiary amine is transformed into a quaternary amine bearing an oxygen atom. The reaction is very selective, favoring the nitrogen atom of the pyrrolidine ring in preference to epoxidation of the fullerene cage. The 1H NMR shows an AB quartet splitting pattern, characteristic of nonequivalent hydrogens in the pyrrolidine ring and at a chemical shift displacement of 0.8 ppm downfield. Other methods of characterization are described, including MS, differential scanning calorimetry, thermogravimetric analysis, HPLC, UV/vis, and IR. Conclusive evidence for the formation of an N-oxide moiety is provided by the synthesis, oxidation, and NMR characterization of a novel [60]fulleropyrrolidine containing a 15N isotope, showing an 85 ppm downfield heteroatom chemical shift. Preliminary details of the effects of substitution on the reactivity of the pyrrolidine ring are also reported.

Chromatography, High Pressure Liquid↗

Tissue biodistribution and blood clearance rates of intravenously administered carbon nanotube radiotracers.

Carbon nanotubes (CNT) are intensively being developed for biomedical applications including drug and gene delivery. Although all possible clinical applications will require compatibility of CNT with the biological milieu, their in vivo capabilities and limitations have not yet been explored. In this work, water-soluble, single-walled CNT (SWNT) have been functionalized with the chelating molecule diethylentriaminepentaacetic (DTPA) and labeled with indium ((111)In) for imaging purposes. Intravenous (i.v.) administration of these functionalized SWNT (f-SWNT) followed by radioactivity tracing using gamma scintigraphy indicated that f-SWNT are not retained in any of the reticuloendothelial system organs (liver or spleen) and are rapidly cleared from systemic blood circulation through the renal excretion route. The observed rapid blood clearance and half-life (3 h) of f-SWNT has major implications for all potential clinical uses of CNT. Moreover, urine excretion studies using both f-SWNT and functionalized multiwalled CNT followed by electron microscopy analysis of urine samples revealed that both types of nanotubes were excreted as intact nanotubes. This work describes the pharmacokinetic parameters of i.v. administered functionalized CNT relevant for various therapeutic and diagnostic applications.

Animals↗

Functionalized carbon nanotubes are non-cytotoxic and preserve the functionality of primary immune cells.

Carbon nanotubes are emerging as innovative tools in nanobiotechnology. However, their toxic effects on environment and health have become an issue of strong concern. In the present study, we address the impact of functionalized carbon nanotubes (f-CNTs) on cells of the immune system. We have prepared two types of f-CNTs, following the 1,3-dipolar cycloaddition reaction (f-CNTs 1 and 2) and the oxidation/amidation treatment (f-CNTs 3 and 4), respectively. We have found that both types of f-CNTs are uptaken by B and T lymphocytes as well as macrophages in vitro, without affecting cell viability. Subsequently, the functionality of the different cells was analyzed carefully. We discovered that f-CNT 1, which is highly water soluble, did not influence the functional activity of immunoregulatory cells. f-CNT 3, which instead possesses reduced solubility and forms mainly stable water suspensions, preserved lymphocytes' functionality while provoking secretion of proinflammatory cytokines by macrophages.

Amides↗

Functionalized carbon nanotubes as emerging nanovectors for the delivery of therapeutics.

Functionalized carbon nanotubes (f-CNT) are emerging as a new family of nanovectors for the delivery of different types of therapeutic molecules. The application of CNT in the field of carrier-mediated delivery has become possible after the recent discovery of their capacity to penetrate into the cells. CNT can be loaded with active molecules by forming stable covalent bonds or supramolecular assemblies based on noncovalent interactions. Once the cargos are carried into various cells, tissues and organs they are able to express their biological function. In this review, we will describe the potential of f-CNT to deliver different types of therapeutic molecules.

DNA↗

Applications of carbon nanotubes in drug delivery.

The development of new and efficient drug delivery systems is of fundamental importance to improve the pharmacological profiles of many classes of therapeutic molecules. Many different types of drug delivery systems are currently available. Within the family of nanomaterials, carbon nanotubes (CNT) have emerged as a new alternative and efficient tool for transporting and translocating therapeutic molecules. CNT can be functionalised with bioactive peptides, proteins, nucleic acids and drugs, and used to deliver their cargos to cells and organs. Because functionalised CNT display low toxicity and are not immunogenic, such systems hold great potential in the field of nanobiotechnology and nanomedicine.

Drug Delivery Systems↗

Binding and condensation of plasmid DNA onto functionalized carbon nanotubes: toward the construction of nanotube-based gene delivery vectors.

Carbon nanotubes (CNTs) constitute a class of nanomaterials that possess characteristics suitable for a variety of possible applications. Their compatibility with aqueous environments has been made possible by the chemical functionalization of their surface, allowing for exploration of their interactions with biological components including mammalian cells. Functionalized CNTs (f-CNTs) are being intensively explored in advanced biotechnological applications ranging from molecular biosensors to cellular growth substrates. We have been exploring the potential of f-CNTs as delivery vehicles of biologically active molecules in view of possible biomedical applications, including vaccination and gene delivery. Recently we reported the capability of ammonium-functionalized single-walled CNTs to penetrate human and murine cells and facilitate the delivery of plasmid DNA leading to expression of marker genes. To optimize f-CNTs as gene delivery vehicles, it is essential to characterize their interactions with DNA. In the present report, we study the interactions of three types of f-CNTs, ammonium-functionalized single-walled and multiwalled carbon nanotubes (SWNT-NH3+; MWNT-NH3+), and lysine-functionalized single-walled carbon nanotubes (SWNT-Lys-NH3+), with plasmid DNA. Nanotube-DNA complexes were analyzed by scanning electron microscopy, surface plasmon resonance, PicoGreen dye exclusion, and agarose gel shift assay. The results indicate that all three types of cationic carbon nanotubes are able to condense DNA to varying degrees, indicating that both nanotube surface area and charge density are critical parameters that determine the interaction and electrostatic complex formation between f-CNTs with DNA. All three different f-CNT types in this study exhibited upregulation of marker gene expression over naked DNA using a mammalian (human) cell line. Differences in the levels of gene expression were correlated with the structural and biophysical data obtained for the f-CNT:DNA complexes to suggest that large surface area leading to very efficient DNA condensation is not necessary for effective gene transfer. However, it will require further investigation to determine whether the degree of binding and tight association between DNA and nanotubes is a desirable trait to increase gene expression efficiency in vitro or in vivo. This study constitutes the first thorough investigation into the physicochemical interactions between cationic functionalized carbon nanotubes and DNA toward construction of carbon nanotube-based gene transfer vector systems.

Cations↗

C3-symmetric peptide scaffolds are functional mimetics of trimeric CD40L.

Interaction between CD40, a member of the tumor necrosis factor receptor (TNFR) superfamily, and its ligand CD40L, a 39-kDa glycoprotein, is essential for the development of humoral and cellular immune responses. Selective blockade or activation of this pathway provides the ground for the development of new treatments against immunologically based diseases and malignancies. Like other members of the TNF superfamily, CD40L monomers self-assemble around a threefold symmetry axis to form noncovalent homotrimers that can each bind three receptor molecules. Here, we report on the structure-based design of small synthetic molecules with C3 symmetry that can mimic CD40L homotrimers. These molecules interact with CD40, compete with the binding of CD40L to CD40, and reproduce, to a certain extent, the functional properties of the much larger homotrimeric soluble CD40L. Architectures based on rigid C3-symmetric cores may thus represent a general approach to mimicking homotrimers of the TNF superfamily.

Animals↗

Carbon nanotubes: on the road to deliver.

Over the last few years, considerable advances have been made in the field of nanotechnology. The advent of carbon nanotube functionalization has paved the way for their potential application as a delivery system of diverse molecules such as peptides, proteins, plasmid DNA, and synthetic oligodeoxynucleotides. This opens new therapeutic and preventive opportunities to combat diseases. The scope of this review is to summarize our recent work in this rapidly growing field.

Carbon↗

Biomedical applications of functionalised carbon nanotubes.

The organic functionalisation of carbon nanotubes can improve substantially their solubility and biocompatibility profile; as a consequence, their manipulation and integration into biological systems has become possible so that functionalised carbon nanotubes hold currently strong promise as novel systems for the delivery of drugs, antigens and genes.

Antigens↗