Giovanna Mancini

Giovanna Mancini
Italian National Research Council | CNR

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178
Publications
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Publications

Publications (178)
Article
Hypothesis The positive charge on liposome surface is known to promote the crossing of the Blood brain barrier (BBB). However, when diastereomeric cationic gemini amphiphiles are among lipid membrane components, also the stereochemistry may affect the permeability of the vesicle across the BBB. Experiments Liposomes featuring cationic diasteromeri...
Article
Full-text available
The C1858T variant of the protein tyrosine phosphatase N22 ( PTPN22 ) gene is associated with pathophysiological phenotypes in several autoimmune conditions, namely, Type 1 diabetes and autoimmune thyroiditis. The R620W variant protein, encoded by C1858T, leads to a gain of function mutation with paradoxical reduced T cell activation. We previously...
Article
Glucosylated liposomes composed of the natural saturated phospholipid 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), cholesterol (Chol) and a cationic amphiphile featuring a glucosyl moiety (GL4), have been developed for delivering the antimicrobial trans-Resveratrol (RSV) to S. epidermidis, characterized by carbohydrate-specific adhesins able...
Article
Full-text available
Though liposome-based drugs are in clinical use, the mechanism of cell internalization of liposomes is yet an object of controversy. The present experimental investigation, carried out on human glioblastoma cells, indicated different internalization routes for two diastereomeric liposomes. Molecular dynamics simulations of the lipid bilayers of the...
Chapter
In this chapter we describe: (1) the procedure for the synthesis of four single chain bolaamphiphiles, displaying chains of 12, 16, 20 and 30 methylene units and triphenylphosphonium moieties as headgroups (TPP1-TPP4); (2) the methods used to characterize TPP1-TPP4 spontaneous aggregation in aqueous solution. We illustrate the determination of Kraf...
Article
Novel cationic glycoliposomes, composed of 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC), cholesterol (Chol) and glycoamphiphiles (featuring a galactosyl, mannosyl or glucosyl moiety) have been investigated for the targeted delivery of trans-resveratrol (RSV), a Quorum Sensing Inhibitor, to Methicillin Resistant Staphylococcus Aureus (MRSA) biofi...
Article
Three new fluorescent molecular rotors were synthesized with the aim of using them as sensors to dose thymidine phosphorylase, one of the target enzymes of 5-fluorouracil, a potent chemotherapic drug largely used in the treatment of many solid tumors, that acts by hindering the metabolism of pyrimidines. 5-Fluorouracil has a very narrow therapeutic...
Article
In the wide panorama of diacetylenic lipids the photo-responsive conjugated 1,3-diyne function is usually encased into the hydrocarbon chain of the amphiphile at variable distance from the headgroup. Therefore, the polydiacetylene network obtained by polymerization upon UV irradiation of the corresponding liposomes, exploited as sensing function, i...
Article
Full-text available
Autophagy is a mechanism involved in many human diseases and in cancers can have a cytotoxic/cytostatic or protective action, being in the latter case involved in multidrug resistance. Understanding which of these roles autophagy has in cancer is thus fundamental for therapeutical decisions because it permits to optimize the therapeutical approach...
Article
Because of the increased incidence of infections caused by resistant pathogens, due to the intensive use of antibiotics, there is an urgent need to develop new therapeutic strategies against bacteria, possibly based on non conventional drugs. (+)-Usnic acid is a natural compound that exerts a potent antibacterial activity, however its clinical appl...
Article
The plant alkaloid voacamine (VOA) displays many interesting pharmacological activities thus, considering its scarce solubility in water, its encapsulation into liposome formulations for its delivery is an important goal. Different cationic liposome formulations containing a phospholipid, cholesterol and one of two diasteromeric cationic surfactant...
Article
Full-text available
In autoimmune diseases as Type 1 diabetes, the actual treatment that provides the missing hormones is not able, however, to interrupt the underlining immunological mechanism. Importantly, novel immunotherapies are exploited to protect and rescue the remaining hormone producing cells. Among probable targets of immunotherapy, the C1858T mutation in t...
Article
The micellization of chiral enantiopure surfactants, dodecyl-N,N-dimethyl-N-(S)-(1-phenyl)ethylammonium bromide and hexadecyl-N,N-dimethyl-N-(S)-(1-phenyl)ethylammonium bromide, was investigated by circular dichroism spectroscopy and isothermal titration calorimetry. The formation of wormlike micelles upon addition of sodium salicylate to the aqueo...
Article
Hypothesis: Bolaamphiphiles are characterized by wide polymorphism of their aggregates, due to the connection of the headgroups that renders their investigation very intriguing in several technological applications. Some bolaamphiphiles displaying the triphenylphosphonium motif (TPP-bolaamphiphiles) were previously explored for their ability in cr...
Article
Phase properties and lateral distribution of components in lipid membranes are frequently investigated by fluorescence of pyrene-labeled lipids. In particular conditions, at specific component molar fractions, lipid bilayers can present regions organized in regular arrangements, hexagonal lattices, where the acyl chain form regular patterns around...
Article
Identification and quantification of bacteria affecting human life, directly causing diseases and indirectly contaminating natural ecosystems, are mostly carried out by expensive and time-consuming methods. There is the need for rapid and economic ways for detecting bacteria in the environment and in clinics. We propose the use of engineered liposo...
Article
The presence of carbohydrate-binding proteins (i.e. lectins) on the surface of various bacterial strains and their overexpression in some tumor tissues makes the use of glycosylated liposomes a promising approach for the specific drug delivery in antibacterial and anti-cancer therapies. However, the functionalization of liposome surface with sugar...
Article
The use of chiral surfactants results in a powerful tool to form chiral assemblies of (L)proline-functionalized porphyrin derivatives in EtOH/H2O exploiting hydrophobic effect. The formation of chiral heteroaggregated species strictly depends both on the configuration of the chiral center of the surfactant and on its concentration, opening the poss...
Article
Full-text available
Type 1 diabetes and thyroid disease are T cell-dependent autoimmune endocrinopathies. The standard substitutive administration of the deficient hormones does not halt the autoimmune process; therefore, development of immunotherapies aiming to preserve the residual hormonal cells, is of crucial importance. PTPN22 C1858T mutation encoding for the R62...
Data
Cell line authentication results. Genetic characteristics were determined by PCR-single-locus-technology on genomic DNA derived from Jurkat cells used for this study. Twenty-one independent PCR-systems were investigated (Eurofins Medigenomix Forensik GmbH, Ebersberg, Germany). Obtained data were searched and compared with online databases of human...
Data
Lyp protein expression in Jurkat T cells 48 hours after the beginning of O/N transfection with different doses of siRNA s/a in DMPC/2/siRNA lipoplexes. (A) Lyp expression in Jurkat T cells cultured in RPMI or after O/N transfection with DMPC/2, 20 pmols of siRNA (siRNA20) and 20 pmols of siRNA complexed in DMPC/2/siRNA lipoplexes (DMPC/2/siRNA20)....
Data
Lyp protein expression in a healthy volunteer PBMC 72 hours after the beginning of O/N transfection with different doses of siRNA s/a in DMPC/1/siRNA lipoplexes. Figure shows representative WB image with all experimental groups. Cells were transfected with empty liposome, 100 pmols of siRNA alone, DMPC/1/siRNA 60, 80 and 100 pmols or cultured in RP...
Data
Chemical structure of liposomal formulations. (TIF)
Data
Additional WB image. Results of siRNA1 transfection of Jurkat T cells with the commercial transfection system. (TIF)
Data
Analysis of Lyp protein expression in Jurkat T cells 48 and 72 hours after each transfection period with different doses of siRNA s/a complexed in DMPC/1/siRNA lipoplexes. Graphs show the analysis of Lyp protein expression 48 (upper panel) and 72 hours (lower panel) after the three different transfection periods in all control and lipoplexes treate...
Data
Analysis of Lyp protein expression in Jurkat T cells 48 and 72 hours after each transfection period with different doses of siRNA s/a complexed in DMPC/2/siRNA lipoplexes. Lyp protein expression 48 (upper panel) and 72 hours (lower panel) after transfection periods in all control and lipoplexes treated groups. DMPC/2: n = 8; RPMI: n = 7; siRNA100:...
Data
Analysis of Lyp protein expression in PBMC 48 and 72 hours after each transfection period with different doses of siRNA s/a complexed in DMPC/2/siRNA lipoplexes. Lyp protein expression 48 and 72 hours after the O/N transfection period in all control and lipoplexes treated groups. DMPC/2: n = 7; RPMI: n = 7; siRNA100: n = 3; DMPC/2/siRNA60: n = 3; D...
Data
PBMC DMPC/2/siRNA internalization. HD PBMC were administered with the indicated formulation marked with rhodamine and relative controls. After 4 and a half hours of treatment cells were fixed and stained for confocal microscopy. (A) Three stainings were performed on PBMC by using: FITC anti human CD3 (green) antibody to specifically label T cells,...
Data
IL-2 detection ELISA assay of culture supernatants. Histogram shows the increase in IL-2 production from anti-CD3/CD28 beads treated Jurkat cells specifically after DMPC/2/siRNA administration at different doses. * indicates p<0.05. (TIF)
Data
Proliferative assay of DMPC/2/siRNA Jurkat T cells. Values of median fluorescence intensity (MFI) indicative of proliferation obtained from CMFDA-labelled Jurkat T cells after 48 and 72 hours from the beginning of transfection with DMPC/2 lipoplexes respect to untransfected cells. (DOCX)
Data
Lyp protein expression in a healthy donor PBMC 72 hours after the beginning of O/N transfection with different doses of siRNA s/a in DMPC/2/siRNA lipoplexes. (TIF)
Data
IL-2 detection ELISA assay of culture supernatants. Histograms illustrate the unresponsiveness of IL-2 upon 24 (A, C) or 48 (B, D) hours of PMA/IONO (PMA-Ionomycin) stimulation in Jurkat T cells previously transfected with DMPC/2 liposomal formulation. US = control unstimulated cells; H = hours; PMA/IONO = transfected Jurkat T cells following activ...
Data
Design of siRNA duplexes to PTPN22. Table reports the design of duplex siRNAs SNP_C (s and a) against the wild type PTPN22 allele. SNPs were designed by genetists at Sigma Chemical Co. (DOCX)
Data
DMPC/1/siRNA and DMPC/2/siRNA treatment of PBMC. Results obtained after 48 (A, C) and 72 hours (B, D) from the beginning of the transfection are listed. (DOCX)
Article
Poly(ethylene glycol) (PEG) stabilized liposomes are widely used in drug delivery research because these surface grafted polymers stabilize liposomes in blood stream. However, hydrophilic polymers also affect lipid membrane organization and it is fundamental to investigate their effect on the physicochemical properties of lipid bilayers as well as...
Article
5-Fluorouracil is a chemotherapic drug widely employed to treat a wide range of solid tumors. Unfortunately, it has a narrow therapeutic window and the level of its target enzymes in biological fluids of patients can vary considerably. On these premises a new fluorescent lipid based sensor for the detection of thymidine phosphorylase, one of the ta...
Article
Background: Steroidal ribbons (or steroid containing ribbons) are being studied for several reasons, firstly, they may be included in the lipid bilayer, especially if they have suitable size (as "extended cholesterol"), and they are interesting in binding to steroidal receptors, gelators, and/or superassembly synthons. Bile acids seem to be very su...
Article
A series of porphyrins with directly meso-attached “sucrose” moiety by the carbon C-6(Formula presented.) of its “fructose” end was synthesized, and their physico-chemical and aggregation properties studied by spectroscopic (fluorescence, circular dichroism, resonance light scattering) techniques. The effect of selected porphyrins on tumor cells wa...
Article
The inclusion of pH-sensitive components in liposome formulations can allow a more controlled and efficient release in response to low pH typical of some pathological tissues and/or subcellular compartments. On the other hand decorating the surface of liposomes with sugar moieties attributes to lipid vesicles specificity toward lectins, sugar-bindi...
Article
The aggregation properties of a new cationic fluorescent amphiphile tagged on the hydrophobic tail with a pyrene moiety and bearing two hydroxyethyl functionalities on the polar headgroup were investigated by fluorescence experiments as pure components or in mixed liposomes containing an unsaturated phospholipid, 1,2‐dioleoyl-sn-glycero-3-phosphoch...
Article
Over the past few years, chiral supramolecular assemblies have been successfully used for recognition, sensing and enantioselective transformations. Several approaches are available to control chirality of discrete assemblies (e.g. cages and capsules), but few are efficient in assuring chirality for micellar aggregates. Optically active amino acid-...
Article
In a previous investigation, cationic liposomes formulated with new 5-FU derivatives, differing for the length of the polyoxyethylenic spacer that links the N3 position of 5-FU to an alkyl chain of 12 carbon atoms, showed a higher cytotoxicity compared to free 5-FU, the cytotoxic effect being directly related to the length of the spacer. To better...
Article
Full-text available
Rationale: Sulfur-vulcanized rubber is a three-dimensional polymer network, insoluble in all organic solvents. For this reason, vulcanization products are difficult to study and identify by conventional analytical techniques. To simplify this task, low molecular weight olefins have been used as model compounds (MCs) in place of rubber in vulcaniza...
Article
Pyrene lipids are useful tools to investigate membrane organization and intracellular lipid trafficking. The molecular interactions controlling the organization of lipid monolayers composed of a cationic amphiphile tagged with a pyrene residue and a saturated or unsaturated phospholipid, namely 1,2-dimyristoyl-sn-glycero-phosphocholine and 1,2-diol...
Article
An investigation, based on absorption and circular dichroism spectroscopy, was carried out on assemblies formed in water upon the interaction of heteroaggregates, composed of dyes (Congo Red or Evans Blue) and cetyltrimethylammonium bromide (CTAB), with four enantiopure phopshocholines (DMPC, DPPC, DOPC, and POPC) characterized by the same polar he...
Article
Full-text available
5-Fluorouracil (5-FU) is widely employed in the treatment of some of the most frequently occurring malig- nant tumours such as breast, colon, and skin cancer. Unfortunately, 5-FU exhibits high toxicity and low tumor affinity with the risk of limited effectiveness and severe side effects for the patients. Numerous deriv- atives have been synthesized...
Article
The investigation of certain features of liposomes such as their lipid bilayer permeability or their propensity to fuse, quite often relies on the entrapment in the internal aqueous compartment of hydrophilic molecules whose optical properties change when they are released into the bulk. However, though defined as probes, these molecules bear funct...
Article
The anthraquinone compound Aloe-Emodin (AE) has shown antineoplastic, antibacterial, antiviral, anti-inflammatory properties and scavenging activity on free radicals. Due to these therapeutic features, AE has been attracting increasing interest and could be applied in the cure of many diseases. However, up to now the physicochemical features of thi...
Article
Full-text available
One of the pharmacological properties of plant alkaloid voacamine is its capability of reverting resistance of tumor cells to doxorubicin, without any intrinsic toxicity. The amine functions of voacamine were exploited to load it with a high efficacy in the internal aqueous compartment of cationic liposomes, formulated with DOPC, a cationic gemini...
Article
Self-assembly of a chiral amphiphilic Zn(II)porphyrin derivative in water gave CD silent species. If the aggregation process occurs in aqueous solutions of chiral surfactants, CD active species are formed with a highly specific molecular recognition effect.
Article
The specificity of carbohydrate-lectin interaction has been reported as an attractive strategy for drug delivery in cancer therapy because of the high levels of lectins in several human malignancies. A novel cationic glucosylated amphiphile was therefore synthesized, as a model system, to attribute specificity toward D-glucose receptors to liposome...
Article
Cationic liposomes have been intensively studied both in basic and applied research because of their promising potential as non viral molecular vehicles. Based on our previous studies [Cosimati et al. Biochim. Biophys. Acta (2013) 1828, 352], this work was aimed to gain more information on the interactions between the plasma membrane and liposomes...
Article
Interaction of the racemic helical homo-octapeptide made by the achiral C(α)-methyl alanine (Aib) amino acid with a chiral enantiopure micellar aggregate made of N-dodecylproline led to the deracemization of the helical Aib sequence thus allowing us to obtain for the first time the CD signature in water of a 310 helix devoid of the contribution of...
Article
An absorption and circular dichroism spectroscopies investigation was carried out on the heteroaggregates formed in water upon the interaction of Chicago Sky Blue with four different cationic surfactants derived from ephedrine and pseudoephedrine and featuring hydrophobic tails of different length. The chirooptical features of the heteroaggregates...
Article
Full-text available
The synthesis, characterization and inclusion in liposomes of a glucosylated bolaamphiphile built on a calix[4]arene scaffold are described. The new glucocalixarene bolaamphiphile destabilizes bilayers of saturated lipids whereas it rigidifies those of unsaturated lipids, thus reducing leakage of calcein from the liposome internal aqueous compartme...
Article
Fluorescently-tagged lipids are a powerful tool for investigating the dynamics of lipids in cell biological studies and in biophysical applications. Herein we report the synthesis and the characterization of a new bola amphiphile, PC12, based on a bisimidic perylene moiety: a central perylene unit is symmetrically linked to two aliphatic chains bot...
Article
In this work a combined theoretical and experimental approach was used to elucidate and describe at the molecular level the basic interactions that drive the transfer of the chiral information from chiral surfactant molecules to dye/surfactant assemblies. It was found that both hydrophobic interactions and relative concentrations strongly influence...
Article
The electrorotation technique was utilized to investigate the interactions between a mouse fibroblast cell line and zwitterionic liposomes formed by a natural phospholipid or cationic liposomes formulated with the same phospholipid and a cationic gemini surfactant. The application of this technique allowed an accurate characterization of the passiv...
Article
Three new pyrrolidinium based surfactants were synthesized and characterized as pure aggregate components and in mixtures with 1,2-dimyristoyl-sn-glycero-3-phosphocholine to understand how the molecular structure of the cationic amphiphile and its mole percentage might affect the physicochemical properties of the resulting aggregates. The thermotro...
Article
Full-text available
The interaction of neutral and anionic phospholipid liposomes, used as cell models, with cationic liposomes formulated with 1,2-dimyristoyl-sn-glicero-3-phosphocholine and stereomeric cationic gemini surfactants was investigated by differential scanning calorimetry, fluorescence experiments and dynamic laser light scattering. This study was aimed a...
Article
Full-text available
The physicochemical features of mixed cationic liposomes formulated with 1,2-dimyristoyl-sn-glycero-3-phosphatidylcoline and one of three stereomeric cationic gemini surfactants were investigated by differential scanning calorimetry, fluorescence, TEM and dynamic laser light scattering. Actually, it was shown that the different stereochemistry of t...
Article
Enantiopure 5-alkyl-4-methyl-2(5H)-furanones reacted by [2+2] photochemical cycloaddition with several trialkylsilylacetylenes to afford regioselectively 3-oxabicyclo[3.2.0]hept-6-en-2-ones silylated at the vinylic C-7 atom. The possible reasons for such regioselectivity are discussed. The anti/syn stereoselectivity of the photocycloaddition depend...
Article
Previous investigations showed that the extent of DNA condensation and the efficiency in the transfection of liposomes formulated with 1,2-dimyristoyl-sn-glycero-phosphocholine and cationic stereomeric gem-ini surfactants depend heavily on the stereochemistry of the gemini. The influence of the stereochemistry on the interaction of lipoplexes with...
Article
Full-text available
The deracemization of bilirubin in micellar aggregates of structurally correlated chiral surfactants was studied by circular dichroism experiments and exploited as the marker of the expression of chirality of the aggregates. The obtained results suggest that the hydrophobic interactions control the transfer of chirality from the monomers to the agg...
Article
Solvent-driven aggregation of a series of porphyrin derivatives was studied by UV/Vis and circular dichroism spectroscopy. The porphyrins are characterised by the presence in the meso positions of steroidal moieties further conjugated with glucosyl groups. The presence of these groups makes the investigated macrocycles amphiphilic and soluble in aq...
Article
Full-text available
Four cationic amphiphilic fluorescent probes were synthesized and fully characterized. All amphiphiles feature a pyrrolidinium headgroup and a hydrocarbon tail tagged with a pyrene residue, and differ in the connection between the headgroup and the tagged tail, and in the hydrophilic/hydrophobic balance, two being single tail surfactants and the ot...
Article
Cationic liposomes are studied mainly as nonviral nucleic acid delivery systems and to a lesser extent as carriers/adjuvants of vaccines and as low-molecular-weight drug carriers. It is well established that the performance and the biological activity of liposomes in general are strongly related to their physicochemical properties. We investigated...
Article
Full-text available
The phase diagram of an amidic surfactant, sodium N-dodecanoylprolinate, was investigated by experimental means such as optical microscopy, multinuclear NMR, and SAXS experiments, and by dissipative particle dynamics and all-atoms molecular dynamics simulations. The organization in domains based on the stereochemical information of the surfactant (...
Article
The interaction of phosphatidylcholine liposomes used as cell models, with cationic liposomes formulated with 1,2-dimyristoyl-sn-glycero-3-phosphatidylcholine and amphiphiles based on a pyrrolidinium headgroup was investigated by differential scanning calorimetry and fluorescence resonance energy transfer experiments. The results obtained showed th...
Article
The aggregates of three new isomeric chiral bola-amphiphiles have been taken into consideration as models for investigating chiral recognition in biological membranes. The recognition capabilities of the aggregates were explored following (by CD and HPLC experiments) the shift in the equilibrium between the inter-converting enantiomers of a bipheny...