107 results on '"Marradi, M."'
Search Results
2. Dual-Targeting Gold Nanoparticles: Simultaneous Decoration with Ligands for Co-Transporters SGLT-1 and B0AT1
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D'Orazio, G, Marradi, M, La Ferla, B, D'Orazio, G, Marradi, M, and La Ferla, B
- Abstract
Sodium–glucose co-transporter 1 (SGLT1) and sodium-dependent neutral amino acid transporter (B0AT1) are mainly expressed on the membrane of enterocytes, a type of epithelial cell found in the intestines. In addition to their physiological role in the absorption of nutrients, a protective role in the integrity of the intestinal barrier has been established. The natural ligands of SGLT1 (d-glucose) and of B0AT1 (l-glutamine) can trigger a protective anti-inflammatory effect on the intestinal epithelium. The literature suggests the activation of common intracellular pathways upon engagement of the two transporters, whose functional forms are composed of oligomers or clusters. Simultaneous activation of these two co-transporters could lead to a potential multitarget and synergistic anti-inflammatory effect. Therefore, nanoplatforms containing multiple copies of the ligands could represent chemical tools to study the potential simultaneous activation of the two co-transporters. For these reasons, in this study, a set of different gold nanoparticles decorated with derivatives of d-glucose and of l-glutamine were designed and prepared. In particular, the synthesis of suitable sulfur-ending functionalized ligand derivatives, including a C-glucoside derivative, their anchoring to gold nanoparticles and their physical–chemical characterization have been carried out. The obtained nanostructures could represent promising multifunctional platforms for further investigation of the existence of possible multitarget and synergistic effects toward the two co-transporters SGLT1 and B0AT1.
- Published
- 2024
3. Antimicrobial Peptide-Loaded Nanoparticles as Inhalation Therapy for Pseudomonas aeruginosa Infections
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Falciani C, Zevolini F, Brunetti J, Riolo G, Gracia R, Marradi M, Loinaz I, Ziemann C, Cossío U, Llop J, Bracci L, and Pini A
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antimicrobial peptides ,nanoparticles ,multi-drug resistance. ,Medicine (General) ,R5-920 - Abstract
Chiara Falciani, 1 Fabrizia Zevolini, 1 Jlenia Brunetti, 1 Giulia Riolo, 2 Raquel Gracia, 3 Marco Marradi, 3 Iraida Loinaz, 3 Christina Ziemann, 4 Unai Cossío, 5 Jordi Llop, 5, 6 Luisa Bracci, 1 Alessandro Pini 1 1Department of Medical Biotechnologies, University of Siena, Siena, Italy; 2Setlance, Siena, Italy; 3CIDETEC, Basque Research and Technology Alliance (BRTA), Donostia-San Sebastián, Spain; 4Fraunhofer Institute for Toxicology and Experimental Medicine ITEM, Hannover, Germany; 5CIC biomaGUNE, Basque Research and Technology Alliance (BRTA), San Sebastian, Spain; 6Centro de Investigación Biomédica en red Enfermedades Respiratorias – CIBERES, Madrid, SpainCorrespondence: Chiara FalcianiDepartment of Medical Biotechnologies, University of Siena, via Aldo Moro 2, Siena, ItalyTel +39 0577 232022Email chiara.falciani@unisi.itIntroduction: Antibiotic-resistant bacteria kill 25,000 people every year in the EU. Patients subject to recurrent lung infections are the most vulnerable to severe or even lethal infections. For these patients, pulmonary delivery of antibiotics would be advantageous, since inhalation can achieve higher concentration in the lungs than iv administration and can provide a faster onset of action. This would allow for the delivery of higher doses and hence reduce the number of treatments required. We report here about a new nanosystem (M33-NS) obtained by capturing SET-M33 peptide on single-chain dextran nanoparticles. SET-M33 is a non-natural antimicrobial peptide synthesized in branched form. This form gives the peptide resistance to degradation in biological fluids. SET-M33 has previously shown efficacy in vitro against about one hundred of Gram-negative multidrug and extensively drug-resistant clinical isolates and was also active in preclinical infection models of pneumonia, sepsis and skin infections.Methods: The new nanosystem was evaluated for its efficacy in bacteria cells and in a mouse model of pneumonia. Toxicity and genotoxicity were also tested in vitro. Biodistribution and pharmacokinetic studies in healthy rats were carried out using a radiolabeled derivative of the nanosystem.Results: The M33-nanosystem, studied here, showed to be effective against Pseudomonas aeruginosa in time-kill kinetic experiments. Cytotoxicity towards different animal cell lines was acceptable. Lung residence time of the antimicrobial peptide, administered via aerosol in healthy rats, was markedly improved by capturing SET-M33 on dextran nanoparticles. M33-NS was also efficient in eradicating pulmonary infection in a BALB/c mouse model of pneumonia caused by P. aeruginosa.Discussion: This study revealed that the encapsulation of the antimicrobial peptide in dextran nanoparticles markedly improved lung residence time of the peptide administered via aerosol. The result has to be considered among the aims of the development of a new therapeutic option for patients suffering recurrent infections, that will benefit from high local doses of persistent antimicrobials.Keywords: antimicrobial peptides, nanoparticles, multi-drug resistance
- Published
- 2020
4. Gold Glyconanoparticles Combined with 91–99 Peptide of the Bacterial Toxin, Listeriolysin O, Are Efficient Immunotherapies in Experimental Bladder Tumors
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Teran-Navarro, H., Zeoli, A., Salines-Cuevas, D., Marradi, M., Montoya, N., Gonzalez-Lopez, E., Ocejo-Vinyals, J. G., Dominguez-Esteban, M., Gutierrez-Banos, J. L., Campos-Juanatey, F., Yanez-Diaz, S., Garcia-Castano, A., Rivera, F., Duran, I., and Alvarez-Dominguez, C.
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bladder cancer ,immunotherapy ,listeriolysin O ,melanoma ,nanoparticles ,peptides ,sugars - Published
- 2022
5. Novel Core-Shell Polyamine Phosphate Nanoparticles Self-Assembled from PEGylated Poly(allylamine hydrochloride) with Low Toxicity and Increased In Vivo Circulation Time
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Andreozzi, P, Simó, C, Moretti, P, Porcel, JM, Lüdtke, TU, Ramirez, MdlA, Tamberi, L, Marradi, M, Amenitsch, H, Llop, J, Ortore, MG, and Moya, SE.
- Abstract
An approach for reducing toxicity and enhancing therapeutic potential of supramolecular polyamine phosphate nanoparticles (PANs) through PEGylation of polyamines before their assembly into nanoparticles is presented here. It is shown that the number of polyethylene glycol (PEG) chains for polyamine largely influence physico-chemical properties of PANs and their biological endpoints. Poly(allylamine hydrochloride) (PAH) are functionalized through carbodiimide chemistry with three ratios of PEG molecules per PAH chain: 0.1, 1, and 10. PEGylated PAH is then assembled into PANs by exposing the polymer to phosphate buffer solution. PANs decrease size and surface charge with increasing PEG ratios as evidenced by dynamic light scattering and zeta potential measurements, with the ten PEG/PAH ratio PANs having practically zero charge. Small angle X-ray scattering (SAXS) proves that PEG chains form a shell around a polyamine core, which is responsible for the screening of positive charges. MTT experiments show that the screening of amine groups decreases nanoparticle toxicity, with the lowest toxicity for the 10 PEG/PAH ratio. Fluorescence correlation spectroscopy (FCS) proves less interaction with proteins for PEGylated PANs. Positron emission tomography (PET) imaging of F-18 labelled PANs shows longer circulation time in healthy mice for PEGylated PANs than non-PEGylated ones.
- Published
- 2021
6. Interfacial activity of modified dextran polysaccharide to produce enzyme-responsive oil-in-water nanoemulsions dagger
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Navascuez, M, Gracia, R, Marradi, M, Diaz, N, Rodriguez, J, Loinaz, I, Lopez-Gallego, F, Llop, J, and Dupin, D
- Abstract
Herein, we report the evaluation of dextran (DXT) derivatives bearing hydrophobic or hydrophilic functional groups as stabilisers of oil-in-water (O/W) emulsions. All investigated modifications conferred interfacial activity to produce stable O/W emulsions, methacrylate(MA)-functionalised DXT being the most promising stabiliser. A minimum amount of MA was required to obtain stable O/W nanoemulsions, which could be degraded in the presence of lipases.
- Published
- 2021
7. Recent advances on smart glycoconjugate vaccines in infections and cancer
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Anderluh, M, Berti, F, Bzducha-Wrobel, A, Chiodo, F, Colombo, C, Compostella, F, Durlik, K, Ferhati, X, Holmdahl, R, Jovanovic, D, Kaca, W, Lay, L, Marinovic-Cincovic, M, Marradi, M, Ozil, M, Polito, L, Reina, JJ, Reis, CA, Sackstein, R, Silipo, A, Svajger, U, Vanek, O, Yamamoto, F, Richichi, B, van Vliet, SJ, RTEÜ, Fen - Edebiyat Fakültesi, Kimya Bölümü, and Özil, Musa
- Subjects
Glycosylation ,Immune system ,Vaccination ,Infection ,Cancer - Abstract
Vaccination is one of the greatest achievements in biomedical research preventing death and morbidity in many infectious diseases through the induction of pathogen-specific humoral and cellular immune responses. Currently, no effective vaccines are available for pathogens with a highly variable antigenic load, such as the human immunodeficiency virus or to induce cellular T-cell immunity in the fight against cancer. The recent SARS-CoV-2 outbreak has reinforced the relevance of designing smart therapeutic vaccine modalities to ensure public health. Indeed, academic and private companies have ongoing joint efforts to develop novel vaccine prototypes for this virus. Many pathogens are covered by a dense glycan-coat, which form an attractive target for vaccine development. Moreover, many tumor types are characterized by altered glycosylation profiles that are known as "tumor-associated carbohydrate antigens". Unfortunately, glycans do not provoke a vigorous immune response and generally serve as T-cell-independent antigens, not eliciting protective immunoglobulin G responses nor inducing immunological memory. A close and continuous crosstalk between glycochemists and glycoimmunologists is essential for the successful development of efficient immune modulators. It is clear that this is a key point for the discovery of novel approaches, which could significantly improve our understanding of the immune system. In this review, we discuss the latest advancements in development of vaccines against glycan epitopes to gain selective immune responses and to provide an overview on the role of different immunogenic constructs in improving glycovaccine efficacy. European Cooperation in Science and Technology (COST) CA18103 Ministry of Education, Youth & Sports - Czech Republic CA18103 LTC20078
- Published
- 2021
8. Cytotoxicity testing of therapeutic nanosystems for pulmonary infection using an air-lifted interphase in-vitro test system
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Knebel, J., primary, Ritter, D., additional, Niehof, M., additional, Hansen, T., additional, Strandh, M., additional, Falciani, C., additional, Flores, M., additional, te Welscher, Y., additional, van Nostrum, C., additional, Gracia, R., additional, Marradi, M., additional, and Loinaz, I., additional
- Published
- 2018
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9. Multimerization of DAB-1 onto Au GNPs affords new potent and selective N-acetylgalactosamine-6-sulfatase (GALNS) inhibitors
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Matassini, C., primary, Vanni, C., additional, Goti, A., additional, Morrone, A., additional, Marradi, M., additional, and Cardona, F., additional
- Published
- 2018
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10. One-pot synthesis of cyclic nitrones and their conversion to pyrrolizidines: 7a-epi-crotanecine inhibits alpha-mannosidases
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Cicchi, S., Marradi, M., Vogel, P., and Goti, A.
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Nitrogen compounds -- Structure ,Nitrogen compounds -- Chemical properties ,Pyrrole -- Chemical properties ,Biological sciences ,Chemistry - Abstract
A new straightforward and inexpensive one-pot procedure is described for the preparation of enantiopure five-membered cyclic nitrones starting from the corresponding lactols. The results show that ((-)-7a-epi-crotanecine) is a potent and selective inhibitor of alpha-mannosidases from jack beans and almonds.
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- 2006
11. Gold glyconanoparticles coupled to listeriolysin O 91–99 peptide serve as adjuvant therapy against melanoma
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Calderon-Gonzalez, R., primary, Terán-Navarro, H., additional, García, I., additional, Marradi, M., additional, Salcines-Cuevas, D., additional, Yañez-Diaz, S., additional, Solis-Angulo, A., additional, Frande-Cabanes, E., additional, Fariñas, M. C., additional, Garcia-Castaño, A., additional, Gomez-Roman, J., additional, Penades, S., additional, Rivera, F., additional, Freire, J., additional, and Álvarez-Domínguez, C., additional
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- 2017
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12. Synthesis and functionalization of dextran-based single-chain nanoparticles in aqueous media
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Gracia, R., primary, Marradi, M., additional, Cossío, U., additional, Benito, A., additional, Pérez-San Vicente, A., additional, Gómez-Vallejo, V., additional, Grande, H.-J., additional, Llop, J., additional, and Loinaz, I., additional
- Published
- 2017
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13. One-Pot Synthesis of Cyclic Nitrones and Their Conversion to Pyrrolizidines: 7a-epi-Crotanecine Inhibits α-Mannosidases
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Marradi M, Stefano Cicchi, Andrea Goti, and Pierre Vogel
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chemistry.chemical_compound ,Enantiopure drug ,Hydroxylamine ,chemistry ,Methanesulfonyl chloride ,Organic Chemistry ,Organic chemistry ,Pyrroline ,Chemoselectivity ,Mannosidases ,Condensation reaction ,Chemical synthesis - Abstract
[reaction: see text] A new straightforward and inexpensive one-pot procedure is described for the preparation of enantiopure five-membered cyclic nitrones starting from the corresponding lactols. Its efficiency relies on the condensation of unprotected hydroxylamine with readily available lactols and on the chemoselectivity of the subsequent esterification with methanesulfonyl chloride. The targeted enantiomerically pure pyrroline N-oxides are versatile synthetic intermediates: one of the nitrones so-obtained has been converted into new polyhydroxypyrrolizidines, analogues of the alkaloids rosmarinecine and crotanecine, which were assayed for their inhibitory activities toward 22 commercially available glycosidase enzymes. One of them ((-)-7a-epi-crotanecine) is a potent and selective inhibitor of alpha-mannosidases from jack beans and almonds.
- Published
- 2006
14. Gold nanoparticles are suitable cores for building tunable iminosugar multivalency
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Universidad de Sevilla. Departamento de Química orgánica, Matassini, Camilla, Marradi, M., Cardona, F., Parmeggiani, C., Robina Ramírez, Inmaculada, Moreno Vargas, Antonio José, Penadés, S., Goti, A., Universidad de Sevilla. Departamento de Química orgánica, Matassini, Camilla, Marradi, M., Cardona, F., Parmeggiani, C., Robina Ramírez, Inmaculada, Moreno Vargas, Antonio José, Penadés, S., and Goti, A.
- Abstract
The first example of iminosugars multimerization based on gold nanoparticle cores was achieved by a straightforward synthetic strategy based on the use of simple glycosides of a-D-mannose or b-Dglucose to modulate the density of biologically active pyrrolizidine and piperidine iminosugars at the gold surface. Exceptionally small and water dispersible gold colloids were obtained by self assembly of thiol ending sugar and novel iminosugar conjugates on the surface of in situ forming gold nanoparticles. The resulting nanostructures were characterized by different techniques. Preliminary screenings demonstrated that the novel nanosized architectures retain their bioactivity and make possible its modulation.
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- 2015
15. Multivalent glycoconjugates as anti-pathogenic agents
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Bernardi, A., Jimenez-Barbero, J., CASNATI, A., Castro, C., DARBRE, T., Fieschi, F., FINNE, J., FUNKEN, H., JAEGER, K., Lahmann, M., Lindhorst, T.K., MARRADI, M., Messner, P., MOLINARO, A., Murphy, P., NATIVI, C., Oscarson, S., Penades, S., Peri, F., Pieters, R., Imberty, A., inconnu, Inconnu, Centre de Recherches sur les Macromolécules Végétales (CERMAV), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF), and Carret, Michèle
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ComputingMilieux_MISCELLANEOUS - Abstract
International audience
- Published
- 2013
16. Influence of ligand presentation density on the molecular recognition of mannose-functionalised glyconanoparticles by bacterial lectin BC2L-A
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Reynolds, M., MARRADI, M., Imberty, A., Penades, S., Perez, S., Centre de Recherches sur les Macromolécules Végétales (CERMAV), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF), European Synchrotron Radiation Facility (ESRF), Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Instituto de Salud Carlos III [Madrid] (ISC)-ministerio de ciencia e innovacion, inconnu, Inconnu, and Carret, Michèle
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[CHIM] Chemical Sciences ,[CHIM]Chemical Sciences ,ComputingMilieux_MISCELLANEOUS - Abstract
International audience; Polyvalent carbohydrate-protein interactions play a key role in bio- and pathological processes, including cell-cell communication and pathogen invasion. In order to study, control and manipulate these interactions gold nanoparticles have been employed as a 3D scaffold, presenting carbohydrate ligands in a multivalent fashion for use as high affinity binding partners and a model system for oligosaccharide presentation at biomacromolecular surfaces. In this study, the binding of a series of mannose-functionalised gold nanoparticles to the dimeric BC2L-A lectin from Burkholderia cenocepacia has been evaluated. BC2L-A is known to exhibit a high specificity for (oligo)mannosides. Due to the unique structure and binding nature of this lectin, it provides a useful tool to study (oligo)saccharides presented on multivalent scaffolds. Surface plasmon resonance and isothermal titration calorimetric assays were used to investigate the effect of ligand presentation density towards binding to the bacterial lectin. We show how a combination of structural complementarities between ligand presentation and lectin architecture and statistical re-binding effects are important for increasing the avidity of multivalent ligands for recognition by their protein receptors; further demonstrating the application of glyconanotechnology towards fundamental glycobiology research as well as a potential towards biomedical diagnostics and therapeutic treatments.
- Published
- 2013
17. Multivalent gold glycoclusters: high affinity molecular recognition by bacterial lectin PA-IL
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Reynolds, M., MARRADI, M., Imberty, A., Penades, S., Perez, S., inconnu, Inconnu, Centre de Recherches sur les Macromolécules Végétales (CERMAV), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF), and Carret, Michèle
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ComputingMilieux_MISCELLANEOUS - Abstract
International audience
- Published
- 2012
18. Visualisation of dual radiolabelled poly(lactide-co-glycolide) nanoparticle degradation in vivo using energy-discriminant SPECT
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Llop, J., primary, Jiang, P., additional, Marradi, M., additional, Gómez-Vallejo, V., additional, Echeverría, M., additional, Yu, S., additional, Puigivila, M., additional, Baz, Z., additional, Szczupak, B., additional, Pérez-Campaña, C., additional, Mao, Z., additional, Gao, C., additional, and Moya, S. E., additional
- Published
- 2015
- Full Text
- View/download PDF
19. Gold nanoparticles are suitable cores for building tunable iminosugar multivalency
- Author
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Matassini, C., primary, Marradi, M., additional, Cardona, F., additional, Parmeggiani, C., additional, Robina, I., additional, Moreno-Vargas, A. J., additional, Penadés, S., additional, and Goti, A., additional
- Published
- 2015
- Full Text
- View/download PDF
20. Confronto delle adesioni alle campagne di screening oncologici tra popolazione italiana e straniera nell'Azienda USL 4 di Prato
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Marradi, M., Nante, N., Epifani, A. C., LA GAMMA, M. L., and Messina, G.
- Published
- 2009
21. Fatti non foste per viver senza screening oncologici: confronto delle adesioni alle campagne di screening tra la popolazione italiana e straniera residente nell' Azienda USL 4 Prato
- Author
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Marradi, M., Epifani, A. C., Lupoli, A., Ruocco, B., Quercioli, C., Messina, G., and Nante, N.
- Published
- 2008
22. Multivalent glycoconjugates as anti-pathogenic agents
- Author
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Bernardi, A, Jiménez Barbero, J, Casnati, A, De Castro, C, Darbre, T, Fieschi, F, Finne, J, Funken, H, Jaeger, K, Lahmann, M, Lindhorst, T, Marradi, M, Messner, P, Molinaro, A, Murphy, P, Nativi, C, Oscarson, S, Penadés, S, Peri, F, Pieters, R, Renaudet, O, Reymond, J, Richichi, B, Rojo, J, Sansone, F, Schäffer, C, Turnbull, W, Velasco Torrijos, T, Vidal, S, Vincent, S, Wennekes, T, Zuilhof, H, Imberty, A, Jaeger, K. E, Lindhorst, TK, Murphy, PV, Pieters, RJ, Reymond, J. L, Turnbull, WB, Imberty, A., PERI, FRANCESCO, Bernardi, A, Jiménez Barbero, J, Casnati, A, De Castro, C, Darbre, T, Fieschi, F, Finne, J, Funken, H, Jaeger, K, Lahmann, M, Lindhorst, T, Marradi, M, Messner, P, Molinaro, A, Murphy, P, Nativi, C, Oscarson, S, Penadés, S, Peri, F, Pieters, R, Renaudet, O, Reymond, J, Richichi, B, Rojo, J, Sansone, F, Schäffer, C, Turnbull, W, Velasco Torrijos, T, Vidal, S, Vincent, S, Wennekes, T, Zuilhof, H, Imberty, A, Jaeger, K. E, Lindhorst, TK, Murphy, PV, Pieters, RJ, Reymond, J. L, Turnbull, WB, Imberty, A., and PERI, FRANCESCO
- Abstract
Multivalency plays a major role in biological processes and particularly in the relationship between pathogenic microorganisms and their host that involves protein–glycan recognition. These interactions occur during the first steps of infection, for specific recognition between host and bacteria, but also at different stages of the immune response. The search for high-affinity ligands for studying such interactions involves the combination of carbohydrate head groups with different scaffolds and linkers generating multivalent glycocompounds with controlled spatial and topology parameters. By interfering with pathogen adhesion, such glycocompounds including glycopolymers, glycoclusters, glycodendrimers and glyconanoparticles have the potential to improve or replace antibiotic treatments that are now subverted by resistance. Multivalent glycoconjugates have also been used for stimulating the innate and adaptive immune systems, for example with carbohydrate-based vaccines. Bacteria present on their surfaces natural multivalent glycoconjugates such as lipopolysaccharides and S-layers that can also be exploited or targeted in anti-infectious strategies.
- Published
- 2013
23. Practical Synthesis of N-Alkyl-N-glycosylhydroxylamines, Multitalented Precursors of Enantiomerically Pure Nitrones
- Author
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Cicchi S., Corsi M., Marradi M., and Goti A.
- Published
- 2002
24. Gold nanoparticles are suitable cores for building tunable iminosugar multivalency.
- Author
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Matassini, C., Marradi, M., Cardona, F., Parmeggiani, C., Robina, I., Moreno-Vargas, A. J., Penadés, S., and Goti, A.
- Published
- 2016
- Full Text
- View/download PDF
25. One-Pot Synthesis of Cyclic Nitrones and Their Conversion to Pyrrolizidines: 7a-epi-Crotanecine Inhibits α-Mannosidases
- Author
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Cicchi, S., primary, Marradi, M., additional, Vogel, P., additional, and Goti, A., additional
- Published
- 2006
- Full Text
- View/download PDF
26. Double Addition of Grignard Reagents to N-Glycosyl Nitrones: A New Tool for the Construction of Enantiopure Azaheterocycles
- Author
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Bonanni, M., Marradi, M., Cicchi, S., Faggi, C., and Goti, A.
- Abstract
C-Phenyl-N-erythrosylnitrone 3 behaves as a C1,C1 bis-electrophile, undergoing a double addition of Grignard reagents in a domino fashion to afford acyclic hydroxylamines4 . The reaction proceeds at 0 °C with variable degrees of diastereoselectivity, from moderate to good, mainly depending on the organomagnesium reagent used. The usefulness of compounds4 has been exemplified with the synthesis of pyrroloazepine12 through a ring closing metathesis key step.- Published
- 2005
27. Emerging glyco-based strategies to steer immune responses
- Author
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Robert Sackstein, Barbara Richichi, Marco Marradi, Alba Silipo, Milena Marinović-Cincović, Wiesław Kaca, Francesco Berti, Urban Švajger, Ondřej Vaněk, Rikard Holmdahl, Sandra J. van Vliet, Fabrizio Chiodo, Katarzyna Durlik, Celso A. Reis, Dragana Jovanovic, Marko Anderluh, Xhenti Ferhati, Josè Juan Reina-Martin, Anna Bzducha-Wróbel, Luigi Lay, Fumiichiro Yamamoto, Laura Polito, Musa Özil, Federica Compostella, Cinzia Colombo, RTEÜ, Fen - Edebiyat Fakültesi, Kimya Bölümü, Özil, Musa, Molecular cell biology and Immunology, AII - Cancer immunology, CCA - Cancer biology and immunology, Anderluh, M., Berti, F., Bzducha-Wrobel, A., Chiodo, F., Colombo, C., Compostella, F., Durlik, K., Ferhati, X., Holmdahl, R., Jovanovic, D., Kaca, W., Lay, L., Marinovic-Cincovic, M., Marradi, M., Ozil, M., Polito, L., Reina-Martin, J. J., Reis, C. A., Sackstein, R., Silipo, A., Svajger, U., Vanek, O., Yamamoto, F., Richichi, B., and van Vliet, S. J.
- Subjects
0301 basic medicine ,Glycan ,glycosylation ,medicine.medical_treatment ,T-Lymphocytes ,Context (language use) ,Computational biology ,Cell Communication ,Biology ,Biochemistry ,Epitope ,Immune tolerance ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Nanoparticle ,Antigen ,Polysaccharides ,medicine ,cancer ,Animals ,Humans ,Polysaccharide ,Molecular Biology ,Receptors, Chimeric Antigen ,Animal ,autoimmunity ,Emerging Methods and Technologies ,Cell Biology ,Immunotherapy ,Glycans, C-type lectins, Immunotherapy ,vaccination ,Chimeric antigen receptor ,3. Good health ,carbohydrates (lipids) ,immune system ,030104 developmental biology ,030220 oncology & carcinogenesis ,biology.protein ,Nanoparticles ,Protein Processing, Post-Translational ,Human - Abstract
Glycan structures are common posttranslational modifications of proteins, which serve multiple important structural roles (for instance in protein folding), but also are crucial participants in cell–cell communications and in the regulation of immune responses. Through the interaction with glycan‐binding receptors, glycans are able to affect the activation status of antigen‐presenting cells, leading either to induction of pro‐inflammatory responses or to suppression of immunity and instigation of immune tolerance. This unique feature of glycans has attracted the interest and spurred collaborations of glyco‐chemists and glyco‐immunologists to develop glycan‐based tools as potential therapeutic approaches in the fight against diseases such as cancer and autoimmune conditions. In this review, we highlight emerging advances in this field, and in particular, we discuss on how glycan‐modified conjugates or glycoengineered cells can be employed as targeting devices to direct tumor antigens to lectin receptors on antigen‐presenting cells, like dendritic cells. In addition, we address how glycan‐based nanoparticles can act as delivery platforms to enhance immune responses. Finally, we discuss some of the latest developments in glycan‐based therapies, including chimeric antigen receptor (CAR)‐T cells to achieve targeting of tumor‐associated glycan‐specific epitopes, as well as the use of glycan moieties to suppress ongoing immune responses, especially in the context of autoimmunity., Glycans are macromolecules that perform crucial roles in development, in cell–cell communication, and in the regulation of immune responses. In this review, we highlight how glycans can be exploited and empowered as treatment or vaccine modalities, particularly in the fight against cancer and autoimmune diseases.
- Published
- 2021
28. Recent advances on smart glycoconjugate vaccines in infections and cancer
- Author
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Musa Özil, José J. Reina, Fabrizio Chiodo, Barbara Richichi, Ondřej Vaněk, Katarzyna Durlik, Cinzia Colombo, Sandra J. van Vliet, Alba Silipo, Federica Compostella, Anna Bzducha-Wróbel, Xhenti Ferhati, Francesco Berti, Milena Marinović-Cincović, Robert Sackstein, Rikard Holmdahl, Luigi Lay, Fumiichiro Yamamoto, Dragana Jovanovic, Marko Anderluh, Wiesław Kaca, Urban Švajger, Marco Marradi, Celso A. Reis, Laura Polito, Anderluh, M., Berti, F., Bzducha-Wrobel, A., Chiodo, F., Colombo, C., Compostella, F., Durlik, K., Ferhati, X., Holmdahl, R., Jovanovic, D., Kaca, W., Lay, L., Marinovic-Cincovic, M., Marradi, M., Ozil, M., Polito, L., Reina, J. J., Reis, C. A., Sackstein, R., Silipo, A., Svajger, U., Vanek, O., Yamamoto, F., Richichi, B., and van Vliet, S. J.
- Subjects
0301 basic medicine ,glycosylation ,Biochemistry ,Immunoglobulin G ,Virus ,Epitope ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Antigen ,Immunity ,Polysaccharides ,Neoplasms ,medicine ,cancer ,Humans ,Molecular Biology ,Vaccines ,biology ,business.industry ,SARS-CoV-2 ,Cancer ,COVID-19 ,Cell Biology ,medicine.disease ,vaccination ,infection ,3. Good health ,Vaccination ,immune system ,030104 developmental biology ,030220 oncology & carcinogenesis ,Immunology ,biology.protein ,business ,Glycoconjugates - Abstract
Vaccination is one of the greatest achievements in biomedical research preventing death and morbidity in many infectious diseases through the induction of pathogen-specific humoral and cellular immune responses. Currently, no effective vaccines are available for pathogens with a highly variable antigenic load, such as the human immunodeficiency virus or to induce cellular T-cell immunity in the fight against cancer. The recent SARS-CoV-2 outbreak has reinforced the relevance of designing smart therapeutic vaccine modalities to ensure public health. Indeed, academic and private companies have ongoing joint efforts to develop novel vaccine prototypes for this virus. Many pathogens are covered by a dense glycan-coat, which form an attractive target for vaccine development. Moreover, many tumor types are characterized by altered glycosylation profiles that are known as “tumor-associated carbohydrate antigens”. Unfortunately, glycans do not provoke a vigorous immune response and generally serve as T-cell-independent antigens, not eliciting protective immunoglobulin G responses nor inducing immunological memory. A close and continuous crosstalk between glycochemists and glycoimmunologists is essential for the successful development of efficient immune modulators. It is clear that this is a key point for the discovery of novel approaches, which could significantly improve our understanding of the immune system. In this review, we discuss the latest advancements in development of vaccines against glycan epitopes to gain selective immune responses and to provide an overview on the role of different immunogenic constructs in improving glycovaccine efficacy.
- Published
- 2021
29. Recent Developments in the Reduction of Oxidative Stress through Antioxidant Polymeric Formulations
- Author
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Andrea Ragusa, Alessandra Quarta, Muhammad Shajih Zafar, Marco Marradi, Zafar, M. S., Quarta, A., Marradi, M., and Ragusa, A.
- Subjects
Antioxidant ,antioxidant ,medicine.medical_treatment ,Radical ,Extract ,polymer ,Pharmaceutical Science ,lcsh:RS1-441 ,Inflammation ,02 engineering and technology ,Review ,010402 general chemistry ,medicine.disease_cause ,film ,01 natural sciences ,lcsh:Pharmacy and materia medica ,Nanoparticle ,medicine ,Cigarette smoke ,Polymer ,extract ,Film ,Chitosan ,Chemistry ,nanoparticle ,ROS ,021001 nanoscience & nanotechnology ,radicals ,0104 chemical sciences ,Hydrogel ,Self-healing hydrogels ,Biophysics ,medicine.symptom ,chitosan ,hydrogel ,0210 nano-technology ,Homeostasis ,Oxidative stress - Abstract
Reactive oxygen and nitrogen species (RONS) are produced endogenously in our body, or introduced through external factors, such as pollution, cigarette smoke, and excessive sunlight exposure. In normal conditions, there is a physiological balance between pro-oxidant species and antioxidant molecules that are able to counteract the detrimental effect of the former. Nevertheless, when this homeostasis is disrupted, the resulting oxidative stress can lead to several pathological conditions, from inflammation to cancer and neurodegenerative diseases. In this review, we report on the recent developments of different polymeric formulations that are able to reduce the oxidative stress, from natural extracts, to films and hydrogels, and finally to nanoparticles (NPs).
- Published
- 2019
30. Multivalent glycoconjugates as anti-pathogenic agents
- Author
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Javier Rojo, Tamis Darbre, Alessandro Casnati, W. Bruce Turnbull, Cristina Nativi, Francesco Peri, Stéphane P. Vincent, Paul V. Murphy, Han Zuilhof, Anna Bernardi, Trinidad Velasco-Torrijos, Franck Fieschi, Anne Imberty, Christina De Castro, Paul Messner, Martina Lahmann, Jean-Reymond Reymond, Sébastien Vidal, Marco Marradi, Jukka Finne, Barbara Richichi, Jesús Jiménez-Barbero, Antonio Molinaro, Olivier Renaudet, Thisbe K. Lindhorst, Horst Funken, Christina Schäffer, Soledad Penadés, Stefan Oscarson, Karl-Erich Jaeger, Roland J. Pieters, Tom Wennekes, Francesco Sansone, Università degli Studi di Milano = University of Milan (UNIMI), Institut de biologie structurale (IBS - UMR 5075 ), Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Biosciences, Glycoscience Group, Bernardi, A, Jiménez Barbero, J, Casnati, A, De Castro, C, Darbre, T, Fieschi, F, Finne, J, Funken, H, Jaeger, K, Lahmann, M, Lindhorst, T, Marradi, M, Messner, P, Molinaro, A, Murphy, P, Nativi, C, Oscarson, S, Penadés, S, Peri, F, Pieters, R, Renaudet, O, Reymond, J, Richichi, B, Rojo, J, Sansone, F, Schäffer, C, Turnbull, W, Velasco Torrijos, T, Vidal, S, Vincent, S, Wennekes, T, Zuilhof, H, Imberty, A, A., Bernardi, J., Jiménez Barbero, A., Casnati, DE CASTRO, Cristina, T., Darbre, F., Fieschi, J., Finne, H., Funken, K. E., Jaeger, M., Lahmann, T. K., Lindhorst, M., Marradi, P., Messner, Molinaro, Antonio, P. V., Murphy, C., Nativi, S., Oscarson, S., Penadé, F., Peri, R. J., Pieter, O., Renaudet, J. L., Reymond, B., Richichi, J., Rojo, F., Sansone, C., Schaffer, W. B., Turnbull, T., Velasco Torrijo, S., Vidal, S., Vincent, T., Wenneke, H., Zuilhof, A., Imberty, Università degli Studi di Milano [Milano] (UNIMI), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)
- Subjects
Lipopolysaccharides ,lectin pa-iil ,Glycoconjugate ,MESH: Virus Internalization ,01 natural sciences ,Bacterial Adhesion ,540 Chemistry ,CHIM/06 - CHIMICA ORGANICA ,carbohydrates, sugars, multivalency, bacteria ,Pathogen ,chemistry.chemical_classification ,[SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM] ,biology ,MESH: HIV ,Organische Chemie ,3. Good health ,DC-SIGN ,Chemistry ,Biochemistry ,protein-carbohydrate interactions ,MESH: Galectins ,MESH: Immunity, Innate ,cholera-toxin ,dc-sign ,high-affinity ,Galectins ,Bacterial Toxins ,education ,010402 general chemistry ,Article ,Immune system ,Humans ,Protein–carbohydrate interactions ,MESH: Bacterial Adhesion ,MESH: Glycoconjugates ,pseudomonas-aeruginosa biofilms ,VLAG ,Galectin ,MESH: Humans ,Bacteria ,010405 organic chemistry ,Organic Chemistry ,HIV ,structural basis ,General Chemistry ,Bacteria Present ,Virus Internalization ,biology.organism_classification ,Immunity, Innate ,0104 chemical sciences ,MESH: Bacteria ,MESH: Bacterial Toxins ,chemistry ,biology.protein ,Nanoparticles ,570 Life sciences ,1182 Biochemistry, cell and molecular biology ,fimbriated escherichia-coli ,MESH: Lipopolysaccharides ,Glycoconjugates ,MESH: Nanoparticles ,bacterial lectin ,glycopeptide dendrimers - Abstract
Multivalency plays a major role in biological processes and particularly in the relationship between pathogenic microorganisms and their host that involves protein–glycan recognition. These interactions occur during the first steps of infection, for specific recognition between host and bacteria, but also at different stages of the immune response. The search for high-affinity ligands for studying such interactions involves the combination of carbohydrate head groups with different scaffolds and linkers generating multivalent glycocompounds with controlled spatial and topology parameters. By interfering with pathogen adhesion, such glycocompounds including glycopolymers, glycoclusters, glycodendrimers and glyconanoparticles have the potential to improve or replace antibiotic treatments that are now subverted by resistance. Multivalent glycoconjugates have also been used for stimulating the innate and adaptive immune systems, for example with carbohydrate-based vaccines. Bacteria present on their surfaces natural multivalent glycoconjugates such as lipopolysaccharides and S-layers that can also be exploited or targeted in anti-infectious strategies., The authors acknowledge the support from EU COST Actions CM1102 and COST BM1003. In addition, the work reviewed has been supported by the sources listed in the original publications cited and by institutions mentioned in the affiliation list., The authors also thank the Unit of Information Resources for Research of the Spanish National Research Council (URICI-CSIC) for the co-financing of this publication in Open Access.
- Published
- 2013
31. Transportable hyperspectral imaging setup based on fast, high-density spectral scanning for in situ quantitative biochemical mapping of fresh tissue biopsies.
- Author
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Giannoni L, Marradi M, Scibilia K, Ezhov I, Bonaudo C, Artemiou A, Toaha A, Lange F, Caredda C, Montcel B, Puppa AD, Tachtsidis I, Rückert D, and Pavone FS
- Subjects
- Humans, Biopsy, Glioma diagnostic imaging, Glioma pathology, Glioblastoma diagnostic imaging, Glioblastoma pathology, Equipment Design, Image Processing, Computer-Assisted methods, Imaging, Three-Dimensional methods, Brain diagnostic imaging, Brain pathology, Hyperspectral Imaging methods, Brain Neoplasms diagnostic imaging, Brain Neoplasms pathology
- Abstract
Significance: Histopathological examination of surgical biopsies, such as in glioma and glioblastoma resection, is hindered in current clinical practice by the long time required for the laboratory analysis and pathological screening, typically taking several days or even weeks to be completed., Aim: We propose here a transportable, high-density, spectral scanning-based hyperspectral imaging (HSI) setup, named HyperProbe1, that can provide in situ , fast biochemical analysis, and mapping of fresh surgical tissue samples, right after excision, and without the need for fixing, staining nor compromising the integrity of the tissue properties., Approach: HyperProbe1 is based on spectral scanning via supercontinuum laser illumination filtered with acousto-optic tunable filters. Such methodology allows the user to select any number and type of wavelength bands in the visible and near-infrared range between 510 and 900 nm (up to a maximum of 79) and to reconstruct 3D hypercubes composed of high-resolution (4 to 5 μ m ), widefield images ( 0.9 × 0.9 mm 2 ) of the surgical samples, where each pixel is associated with a complete spectrum., Results: The HyperProbe1 setup is here presented and characterized. The system is applied to 11 fresh surgical biopsies of glioma from routine patients, including different grades of tumor classification. Quantitative analysis of the composition of the tissue is performed via fast spectral unmixing to reconstruct the mapping of major biomarkers, such as oxy-( HbO 2 ) and deoxyhemoglobin (HHb), as well as cytochrome-c-oxidase (CCO). We also provided a preliminary attempt to infer tumor classification based on differences in composition in the samples, suggesting the possibility of using lipid content and differential CCO concentrations to distinguish between lower and higher-grade gliomas., Conclusions: A proof of concept of the performances of HyperProbe1 for quantitative, biochemical mapping of surgical biopsies is demonstrated, paving the way for improving current post-surgical, histopathological practice via non-destructive, in situ streamlined screening of fresh tissue samples in a matter of minutes after excision., (© 2024 The Authors.)
- Published
- 2024
- Full Text
- View/download PDF
32. Impact of Tissue Damage and Hemodynamics on Restenosis Following Percutaneous Transluminal Angioplasty: A Patient-Specific Multiscale Model.
- Author
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Corti A, Marradi M, Çelikbudak Orhon C, Boccafoschi F, Büchler P, Rodriguez Matas JF, and Chiastra C
- Subjects
- Humans, Angioplasty, Patient-Specific Modeling, Models, Cardiovascular, Hemodynamics, Femoral Artery physiopathology, Femoral Artery injuries
- Abstract
Multiscale agent-based modeling frameworks have recently emerged as promising mechanobiological models to capture the interplay between biomechanical forces, cellular behavior, and molecular pathways underlying restenosis following percutaneous transluminal angioplasty (PTA). However, their applications are mainly limited to idealized scenarios. Herein, a multiscale agent-based modeling framework for investigating restenosis following PTA in a patient-specific superficial femoral artery (SFA) is proposed. The framework replicates the 2-month arterial wall remodeling in response to the PTA-induced injury and altered hemodynamics, by combining three modules: (i) the PTA module, consisting in a finite element structural mechanics simulation of PTA, featuring anisotropic hyperelastic material models coupled with a damage formulation for fibrous soft tissue and the element deletion strategy, providing the arterial wall damage and post-intervention configuration, (ii) the hemodynamics module, quantifying the post-intervention hemodynamics through computational fluid dynamics simulations, and (iii) the tissue remodeling module, based on an agent-based model of cellular dynamics. Two scenarios were explored, considering balloon expansion diameters of 5.2 and 6.2 mm. The framework captured PTA-induced arterial tissue lacerations and the post-PTA arterial wall remodeling. This remodeling process involved rapid cellular migration to the PTA-damaged regions, exacerbated cell proliferation and extracellular matrix production, resulting in lumen area reduction up to 1-month follow-up. After this initial reduction, the growth stabilized, due to the resolution of the inflammatory state and changes in hemodynamics. The similarity of the obtained results to clinical observations in treated SFAs suggests the potential of the framework for capturing patient-specific mechanobiological events occurring after PTA intervention., (© 2024. The Author(s).)
- Published
- 2024
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33. Gold nanoparticles decorated with monosaccharides and sulfated ligands as potential modulators of the lysosomal enzyme N -acetylgalactosamine-6-sulfatase (GALNS).
- Author
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Buco F, Matassini C, Vanni C, Clemente F, Paoli P, Carozzini C, Beni A, Cardona F, Goti A, Moya SE, Ortore MG, Andreozzi P, Morrone A, and Marradi M
- Subjects
- Gold, Acetylgalactosamine, Monosaccharides, Ligands, Sulfates, Scattering, Small Angle, X-Ray Diffraction, Lysosomes, Metal Nanoparticles, Chondroitinsulfatases
- Abstract
N -Acetylgalactosamine-6-sulfatase (GALNS) is an enzyme whose deficiency is related to the lysosomal storage disease Morquio A. For the development of effective therapeutic approaches against this disease, the design of suitable enzyme enhancers ( i.e. pharmacological chaperones) is fundamental. The natural substrates of GALNS are the glycosaminoglycans keratan sulfate and chondroitin 6-sulfate, which mainly display repeating units of sulfated carbohydrates. With a biomimetic approach, gold nanoparticles (AuNPs) decorated with simple monosaccharides, sulfated ligands (homoligand AuNPs), or both monosaccharides and sulfated ligands (mixed-ligand AuNPs) were designed here as multivalent inhibitors of GALNS. Among the homoligand AuNPs, the most effective inhibitors of GALNS activity are the β-D-galactoside-coated AuNPs. In the case of mixed-ligand AuNPs, β-D-galactosides/sulfated ligands do not show better inhibition than the β-D-galactoside-coated AuNPs. However, a synergistic effect is observed for α-D-mannosides in a mixed-ligand coating with sulfated ligands that reduced IC
50 by one order of magnitude with respect to the homoligand α-D-mannoside-coated AuNPs. SAXS experiments corroborated the association of GALNS with β-D-galactoside AuNPs. These AuNPs are able to restore the enzyme activity by almost 2-fold after thermal denaturation, indicating a potential chaperoning activity towards GALNS. This information could be exploited for future development of nanomedicines for Morquio A. The recent implications of GALNS in cancer and neuropathic pain make these kinds of multivalent bionanomaterials of great interest towards multiple therapies.- Published
- 2023
- Full Text
- View/download PDF
34. Naturalized Dyes: A New Opportunity for the Wood Coloring.
- Author
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Vespignani L, Bonanni M, Marradi M, Pizzo B, Bianchini R, and Goli G
- Abstract
Naturalized dyes (NDs) are innovative and eco-friendly synthetic compounds in which a chromophore is covalently linked to a natural sugar (e.g., lactose). The sugar moiety confers water-solubility and biocompatibility to the dye molecule as a whole. NDs have demonstrated potential application in dyeing textiles and leather. The purpose of this work was to demonstrate that selected NDs can be also applied to dye wood. To that aim, two NDs were tested to color beech and poplar wood. The NDs were applied as a simple aqueous solution or mixed with a waterborne, biogenic staining agent (commercially available Gemma U50). Moreover, the effect of the application of a biogenic waterborne top coat (commercially available Resina Plus U49) was also studied. Different methods were tested to investigate the potential application of these NDs to wood. The dyeing behavior was analyzed in terms of penetration into the substrate, covering capacity and color homogeneity through macro- and microscopic observations and colorimetric measurements. The color fastness to water washout and the color stability to light, in particular by exposing the wooden samples to artificial aging (UV radiations in a Solar Box), were also investigated. The NDs, when used as water solutions, were able to afford a homogeneous coating and a pleasant appearance on the wood surface, as well as a good color fastness to washout with water. Dissolving the dyes in the stain or applying the top coat generally resulted in even better color fastness to washout. However, all the application methods tested showed limited resistance to fading in the Solar Box, which therefore remains a drawback for this type of product.
- Published
- 2023
- Full Text
- View/download PDF
35. Simple engineering of hybrid cellulose nanocrystal-gold nanoparticles results in a functional glyconanomaterial with biomolecular recognition properties.
- Author
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Biagiotti G, Toniolo G, Albino M, Severi M, Andreozzi P, Marelli M, Kokot H, Tria G, Guerri A, Sangregorio C, Rojo J, Berti D, Marradi M, Cicchi S, Urbančič I, van Kooyk Y, Chiodo F, and Richichi B
- Subjects
- Gold chemistry, Cellulose chemistry, Click Chemistry, Lectins, C-Type, Metal Nanoparticles chemistry
- Abstract
Cellulose nanocrystal and gold nanoparticles are assembled, in a unique way, to yield a novel modular glyconanomaterial whose surface is then easily engineered with one or two different headgroups, by exploiting a robust click chemistry route. We demonstrate the potential of this approach by conjugating monosaccharide headgroups to the glyconanomaterial and show that the sugars retain their binding capability to C-type lectin receptors, as also directly visualized by cryo-TEM.
- Published
- 2023
- Full Text
- View/download PDF
36. Neutralization of ionic interactions by dextran-based single-chain nanoparticles improves tobramycin diffusion into a mature biofilm.
- Author
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Blanco-Cabra N, Movellan J, Marradi M, Gracia R, Salvador C, Dupin D, Loinaz I, and Torrents E
- Subjects
- Anti-Bacterial Agents pharmacology, Biofilms, Deoxyribonuclease I, Dextrans, Pseudomonas aeruginosa, Nanoparticles, Tobramycin pharmacology
- Abstract
The extracellular matrix protects biofilm cells by reducing diffusion of antimicrobials. Tobramycin is an antibiotic used extensively to treat P. aeruginosa biofilms, but it is sequestered in the biofilm periphery by the extracellular negative charge matrix and loses its efficacy significantly. Dispersal of the biofilm extracellular matrix with enzymes such as DNase I is another promising therapy that enhances antibiotic diffusion into the biofilm. Here, we combine the charge neutralization of tobramycin provided by dextran-based single-chain polymer nanoparticles (SCPNs) together with DNase I to break the biofilm matrix. Our study demonstrates that the SCPNs improve the activity of tobramycin and DNase I by neutralizing the ionic interactions that keep this antibiotic in the biofilm periphery. Moreover, the detailed effects and interactions of nanoformulations with extracellular matrix components were revealed through time-lapse imaging of the P. aeruginosa biofilms by laser scanning confocal microscopy with specific labeling of the different biofilm components., (© 2022. The Author(s).)
- Published
- 2022
- Full Text
- View/download PDF
37. Recent advances on smart glycoconjugate vaccines in infections and cancer.
- Author
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Anderluh M, Berti F, Bzducha-Wróbel A, Chiodo F, Colombo C, Compostella F, Durlik K, Ferhati X, Holmdahl R, Jovanovic D, Kaca W, Lay L, Marinovic-Cincovic M, Marradi M, Ozil M, Polito L, Reina JJ, Reis CA, Sackstein R, Silipo A, Švajger U, Vaněk O, Yamamoto F, Richichi B, and van Vliet SJ
- Subjects
- Glycoconjugates therapeutic use, Humans, Polysaccharides therapeutic use, SARS-CoV-2, COVID-19 prevention & control, Neoplasms prevention & control, Vaccines
- Abstract
Vaccination is one of the greatest achievements in biomedical research preventing death and morbidity in many infectious diseases through the induction of pathogen-specific humoral and cellular immune responses. Currently, no effective vaccines are available for pathogens with a highly variable antigenic load, such as the human immunodeficiency virus or to induce cellular T-cell immunity in the fight against cancer. The recent SARS-CoV-2 outbreak has reinforced the relevance of designing smart therapeutic vaccine modalities to ensure public health. Indeed, academic and private companies have ongoing joint efforts to develop novel vaccine prototypes for this virus. Many pathogens are covered by a dense glycan-coat, which form an attractive target for vaccine development. Moreover, many tumor types are characterized by altered glycosylation profiles that are known as "tumor-associated carbohydrate antigens". Unfortunately, glycans do not provoke a vigorous immune response and generally serve as T-cell-independent antigens, not eliciting protective immunoglobulin G responses nor inducing immunological memory. A close and continuous crosstalk between glycochemists and glycoimmunologists is essential for the successful development of efficient immune modulators. It is clear that this is a key point for the discovery of novel approaches, which could significantly improve our understanding of the immune system. In this review, we discuss the latest advancements in development of vaccines against glycan epitopes to gain selective immune responses and to provide an overview on the role of different immunogenic constructs in improving glycovaccine efficacy., (© 2021 The Authors. The FEBS Journal published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)
- Published
- 2022
- Full Text
- View/download PDF
38. Gold Glyconanoparticles Combined with 91-99 Peptide of the Bacterial Toxin, Listeriolysin O, Are Efficient Immunotherapies in Experimental Bladder Tumors.
- Author
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Terán-Navarro H, Zeoli A, Salines-Cuevas D, Marradi M, Montoya N, Gonzalez-Lopez E, Ocejo-Vinyals JG, Dominguez-Esteban M, Gutierrez-Baños JL, Campos-Juanatey F, Yañez-Diaz S, Garcia-Castaño A, Rivera F, Duran I, and Alvarez-Dominguez C
- Abstract
This study presents proof of concept assays to validate gold nanoparticles loaded with the bacterial peptide 91-99 of the listeriolysin O toxin (GNP-LLO
91-99 nanovaccines) as immunotherapy for bladder tumors. GNP-LLO91-99 nanovaccines showed adjuvant abilities as they induce maturation and activation of monocyte-derived dendritic cells (MoDCs) to functional antigen-presenting cells in healthy donors and patients with melanoma or bladder cancer (BC), promoting a Th1 cytokine pattern. GNP-LLO91-99 nanovaccines were also efficient dendritic cell inducers of immunogenic tumor death using different bladder and melanoma tumor cell lines. The establishment of a pre-clinical mice model of subcutaneous BC confirmed that a single dose of GNP-LLO91-99 nanovaccines reduced tumor burden 4.7-fold and stimulated systemic Th1-type immune responses. Proof of concept assays validated GNP-LLO91-99 nanovaccines as immunotherapy by comparison to anti-CTLA-4 or anti-PD-1 antibodies. In fact, GNP-LLO91-99 nanovaccines increased percentages of CD4+ and CD8+ T cells, B cells, and functional antigen-presenting DCs in tumor-infiltrated lymphocytes, while they reduced the levels of myeloid-derived suppressor cells (MDSC) and suppressor T cells (Treg ). We conclude that GNP-LLO91-99 nanovaccines can work as monotherapies or combinatory immunotherapies with anti-CTLA-4 or anti-PD-1 antibodies for solid tumors with high T cell infiltration, such as bladder cancer or melanoma.- Published
- 2022
- Full Text
- View/download PDF
39. Hybrid Multivalent Jack Bean α-Mannosidase Inhibitors: The First Example of Gold Nanoparticles Decorated with Deoxynojirimycin Inhitopes.
- Author
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Vanni C, Bodlenner A, Marradi M, Schneider JP, Ramirez MLA, Moya S, Goti A, Cardona F, Compain P, and Matassini C
- Subjects
- 1-Deoxynojirimycin chemistry, Enzyme Inhibitors chemistry, Metal Nanoparticles chemistry, 1-Deoxynojirimycin administration & dosage, Canavalia enzymology, Enzyme Inhibitors administration & dosage, Gold chemistry, Metal Nanoparticles administration & dosage, alpha-Mannosidase antagonists & inhibitors
- Abstract
Among carbohydrate-processing enzymes, Jack bean α-mannosidase (JBα-man) is the glycosidase with the best responsiveness to the multivalent presentation of iminosugar inhitopes. We report, in this work, the preparation of water dispersible gold nanoparticles simultaneously coated with the iminosugar deoxynojirimycin (DNJ) inhitope and simple monosaccharides (β-d-gluco- or α-d-mannosides). The display of DNJ at the gold surface has been modulated (i) by using an amphiphilic linker longer than the aliphatic chain used for the monosaccharides and (ii) by presenting the inhitope, not only in monomeric form, but also in a trimeric fashion through combination of a dendron approach with glyconanotechnology. The latter strategy resulted in a strong enhancement of the inhibitory activity towards JBα-man, with a K
i in the nanomolar range ( Ki = 84 nM), i.e., more than three orders of magnitude higher than the monovalent reference compound.- Published
- 2021
- Full Text
- View/download PDF
40. Novel Core-Shell Polyamine Phosphate Nanoparticles Self-Assembled from PEGylated Poly(allylamine hydrochloride) with Low Toxicity and Increased In Vivo Circulation Time.
- Author
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Andreozzi P, Simó C, Moretti P, Porcel JM, Lüdtke TU, Ramirez MLA, Tamberi L, Marradi M, Amenitsch H, Llop J, Ortore MG, and Moya SE
- Subjects
- Animals, Mice, Polyamines toxicity, Polyethylene Glycols, Scattering, Small Angle, X-Ray Diffraction, Nanoparticles toxicity, Phosphates
- Abstract
An approach for reducing toxicity and enhancing therapeutic potential of supramolecular polyamine phosphate nanoparticles (PANs) through PEGylation of polyamines before their assembly into nanoparticles is presented here. It is shown that the number of polyethylene glycol (PEG) chains for polyamine largely influence physico-chemical properties of PANs and their biological endpoints. Poly(allylamine hydrochloride) (PAH) are functionalized through carbodiimide chemistry with three ratios of PEG molecules per PAH chain: 0.1, 1, and 10. PEGylated PAH is then assembled into PANs by exposing the polymer to phosphate buffer solution. PANs decrease size and surface charge with increasing PEG ratios as evidenced by dynamic light scattering and zeta potential measurements, with the ten PEG/PAH ratio PANs having practically zero charge. Small angle X-ray scattering (SAXS) proves that PEG chains form a shell around a polyamine core, which is responsible for the screening of positive charges. MTT experiments show that the screening of amine groups decreases nanoparticle toxicity, with the lowest toxicity for the 10 PEG/PAH ratio. Fluorescence correlation spectroscopy (FCS) proves less interaction with proteins for PEGylated PANs. Positron emission tomography (PET) imaging of
18 F labelled PANs shows longer circulation time in healthy mice for PEGylated PANs than non-PEGylated ones., (© 2021 Wiley-VCH GmbH.)- Published
- 2021
- Full Text
- View/download PDF
41. Emerging glyco-based strategies to steer immune responses.
- Author
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Anderluh M, Berti F, Bzducha-Wróbel A, Chiodo F, Colombo C, Compostella F, Durlik K, Ferhati X, Holmdahl R, Jovanovic D, Kaca W, Lay L, Marinovic-Cincovic M, Marradi M, Ozil M, Polito L, Reina-Martin JJ, Reis CA, Sackstein R, Silipo A, Švajger U, Vaněk O, Yamamoto F, Richichi B, and van Vliet SJ
- Subjects
- Animals, Cell Communication immunology, Humans, Nanoparticles chemistry, Polysaccharides chemistry, Protein Processing, Post-Translational, Autoimmunity immunology, Polysaccharides immunology, Receptors, Chimeric Antigen immunology, T-Lymphocytes immunology
- Abstract
Glycan structures are common posttranslational modifications of proteins, which serve multiple important structural roles (for instance in protein folding), but also are crucial participants in cell-cell communications and in the regulation of immune responses. Through the interaction with glycan-binding receptors, glycans are able to affect the activation status of antigen-presenting cells, leading either to induction of pro-inflammatory responses or to suppression of immunity and instigation of immune tolerance. This unique feature of glycans has attracted the interest and spurred collaborations of glyco-chemists and glyco-immunologists to develop glycan-based tools as potential therapeutic approaches in the fight against diseases such as cancer and autoimmune conditions. In this review, we highlight emerging advances in this field, and in particular, we discuss on how glycan-modified conjugates or glycoengineered cells can be employed as targeting devices to direct tumor antigens to lectin receptors on antigen-presenting cells, like dendritic cells. In addition, we address how glycan-based nanoparticles can act as delivery platforms to enhance immune responses. Finally, we discuss some of the latest developments in glycan-based therapies, including chimeric antigen receptor (CAR)-T cells to achieve targeting of tumor-associated glycan-specific epitopes, as well as the use of glycan moieties to suppress ongoing immune responses, especially in the context of autoimmunity., (© 2021 The Authors. The FEBS Journal published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)
- Published
- 2021
- Full Text
- View/download PDF
42. Interfacial activity of modified dextran polysaccharide to produce enzyme-responsive oil-in-water nanoemulsions.
- Author
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Navascuez M, Gracia R, Marradi M, Díaz N, Rodríguez J, Loinaz I, López-Gállego F, Llop J, and Dupin D
- Subjects
- Dextrans chemistry, Emulsions chemistry, Emulsions metabolism, Fungal Proteins chemistry, Hydrophobic and Hydrophilic Interactions, Lipase chemistry, Nanoparticles chemistry, Oils chemistry, Particle Size, Water chemistry, Dextrans metabolism, Fungal Proteins metabolism, Lipase metabolism, Nanoparticles metabolism, Oils metabolism, Water metabolism
- Abstract
Herein, we report the evaluation of dextran (DXT) derivatives bearing hydrophobic or hydrophilic functional groups as stabilisers of oil-in-water (O/W) emulsions. All investigated modifications conferred interfacial activity to produce stable O/W emulsions, methacrylate(MA)-functionalised DXT being the most promising stabiliser. A minimum amount of MA was required to obtain stable O/W nanoemulsions, which could be degraded in the presence of lipases.
- Published
- 2021
- Full Text
- View/download PDF
43. The B & B approach: Ball-milling conjugation of dextran with phenylboronic acid (PBA)-functionalized BODIPY.
- Author
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Andreozzi P, Tamberi L, Tasca E, Giacomazzo GE, Martinez M, Severi M, Marradi M, Cicchi S, Moya S, Biagiotti G, and Richichi B
- Abstract
Mechanochemistry is an emerging and reliable alternative to conventional solution (batch) synthesis of complex molecules under green and solvent-free conditions. In this regard, we report here on the conjugation of a dextran polysaccharide with a fluorescent probe, a phenylboronic acid (PBA)-functionalized boron dipyrromethene (BODIPY) applying the ball milling approach. The ball milling formation of boron esters between PBA BODIPY and dextran proved to be more efficient in terms of reaction time, amount of reactants, and labelling degree compared to the corresponding solution-based synthetic route. PBA-BODIPY dextran assembles into nanoparticles of around 200 nm by hydrophobic interactions. The resulting PBA-BODIPY dextran nanoparticles retain an apolar interior as proved by pyrene fluorescence, suitable for the encapsulation of hydrophobic drugs with high biocompatibility while remaining fluorescent., (Copyright © 2020, Andreozzi et al.; licensee Beilstein-Institut.)
- Published
- 2020
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44. Therapeutic Efficacy of Novel Antimicrobial Peptide AA139-Nanomedicines in a Multidrug-Resistant Klebsiella pneumoniae Pneumonia-Septicemia Model in Rats.
- Author
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van der Weide H, Cossío U, Gracia R, Te Welscher YM, Ten Kate MT, van der Meijden A, Marradi M, Ritsema JAS, Vermeulen-de Jongh DMC, Storm G, Goessens WHF, Loinaz I, van Nostrum CF, Llop J, Hays JP, and Bakker-Woudenberg IAJM
- Subjects
- Animals, Anti-Bacterial Agents pharmacology, Anti-Bacterial Agents therapeutic use, Klebsiella pneumoniae, Microbial Sensitivity Tests, Nanomedicine, Rats, Tissue Distribution, Bacteremia drug therapy, Drug Resistance, Multiple, Bacterial, Klebsiella Infections drug therapy, Pneumonia, Bacterial drug therapy, Pore Forming Cytotoxic Proteins pharmacology
- Abstract
Antimicrobial peptides (AMPs) have seen limited clinical use as antimicrobial agents, largely due to issues relating to toxicity, short biological half-life, and lack of efficacy against Gram-negative bacteria. However, the development of novel AMP-nanomedicines, i.e., AMPs entrapped in nanoparticles, has the potential to ameliorate these clinical problems. The authors investigated two novel nanomedicines based on AA139, an AMP currently in development for the treatment of multidrug-resistant Gram-negative infections. AA139 was entrapped in polymeric nanoparticles (PNPs) or lipid-core micelles (MCLs). The antimicrobial activity of AA139-PNP and AA139-MCL was determined in vitro The biodistribution and limiting doses of AA139-nanomedicines were determined in uninfected rats via endotracheal aerosolization. The early bacterial killing activity of the AA139-nanomedicines in infected lungs was assessed in a rat model of pneumonia-septicemia caused by extended-spectrum β-lactamase-producing Klebsiella pneumoniae In this model, the therapeutic efficacy was determined by once-daily (q24h) administration over 10 days. Both AA139-nanomedicines showed equivalent in vitro antimicrobial activities (similar to free AA139). In uninfected rats, they exhibited longer residence times in the lungs than free AA139 (∼20% longer for AA139-PNP and ∼80% longer for AA139-MCL), as well as reduced toxicity, enabling a higher limiting dose. In rats with pneumonia-septicemia, both AA139-nanomedicines showed significantly improved therapeutic efficacy in terms of an extended rat survival time, although survival of all rats was not achieved. These results demonstrate potential advantages that can be achieved using AMP-nanomedicines. AA139-PNP and AA139-MCL may be promising novel therapeutic agents for the treatment of patients suffering from multidrug-resistant Gram-negative pneumonia-septicemia., (Copyright © 2020 American Society for Microbiology.)
- Published
- 2020
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45. In vitro inhalation cytotoxicity testing of therapeutic nanosystems for pulmonary infection.
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Ritter D, Knebel J, Niehof M, Loinaz I, Marradi M, Gracia R, Te Welscher Y, van Nostrum CF, Falciani C, Pini A, Strandh M, and Hansen T
- Subjects
- A549 Cells, Aerosols, Anti-Bacterial Agents administration & dosage, Bacterial Infections drug therapy, Cell Survival drug effects, Humans, Liposomes, Lung drug effects, Lung Diseases drug therapy, Methacrylates administration & dosage, Methacrylates toxicity, Micelles, Nanoparticles administration & dosage, Nylons toxicity, Peptides administration & dosage, Anti-Bacterial Agents toxicity, Nanoparticles toxicity, Peptides toxicity
- Abstract
Due to the increasing need of new treatment options against bacterial lung infections, novel antimicrobial peptides (AMPs) are under development. Local bioavailability and less systemic exposure lead to the inhalation route of administration. Combining AMPs with nanocarriers (NCs) into nanosystems (NSs) might be a technique for improved results. An air-liquid interface (ALI) in vitro inhalation model was set up including a human alveolar lung cell line (A549) and an optimized exposure system (P.R.I.T.® ExpoCube®) to predict acute local lung toxicity. The approach including aerosol controls (cupper-II-sulfate and lactose) delivered lowest observable adverse effect levels (LOAELs). Different combinations of AMPs (AA139, M33) and NCs (polymeric nanoparticles (PNPs), micelles and liposomes) were tested under ALI and submerged in vitro conditions. Depending on the nature of AMP and NCs, packing of AMPs into NSs reduced the AMP-related toxicity. Large differences were found between the LOAELs determined by submerged or ALI testing with the ALI approach indicating higher sensitivity of the ALI model. Since aerosol droplet exposure is in vivo relevant, it is assumed that ALI based results represents the more significant source than submerged testing for in vivo prediction of local acute lung toxicity. In accordance with the current state-of-the-art view, this study shows that ALI in vitro inhalation models are promising tools to further develop in vitro methods in the field of inhalation toxicology., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)
- Published
- 2020
- Full Text
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46. Recent Developments in the Reduction of Oxidative Stress through Antioxidant Polymeric Formulations.
- Author
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Zafar MS, Quarta A, Marradi M, and Ragusa A
- Abstract
Reactive oxygen and nitrogen species (RONS) are produced endogenously in our body, or introduced through external factors, such as pollution, cigarette smoke, and excessive sunlight exposure. In normal conditions, there is a physiological balance between pro-oxidant species and antioxidant molecules that are able to counteract the detrimental effect of the former. Nevertheless, when this homeostasis is disrupted, the resulting oxidative stress can lead to several pathological conditions, from inflammation to cancer and neurodegenerative diseases. In this review, we report on the recent developments of different polymeric formulations that are able to reduce the oxidative stress, from natural extracts, to films and hydrogels, and finally to nanoparticles (NPs)., Competing Interests: The authors declare no conflict of interest.
- Published
- 2019
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47. Pre-clinical development of Listeria -based nanovaccines as immunotherapies for solid tumours: insights from melanoma.
- Author
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Terán-Navarro H, Calderon-Gonzalez R, Salcines-Cuevas D, García I, Marradi M, Freire J, Salmon E, Portillo-Gonzalez M, Frande-Cabanes E, García-Castaño A, Martinez-Callejo V, Gomez-Roman J, Tobes R, Rivera F, Yañez-Diaz S, and Álvarez-Domínguez C
- Abstract
Gold glyconanoparticles loaded with the listeriolysin O peptide 91-99 (GNP-LLO
91-99 ), a bacterial peptide with anti-metastatic properties, are vaccine delivery platforms facilitating immune cell targeting and increasing antigen loading. Here, we present proof of concept analyses for the consideration of GNP-LLO91-99 nanovaccines as a novel immunotherapy for cutaneous melanoma. Studies using mouse models of subcutaneous melanoma indicated that GNP-LLO91-99 nanovaccines recruite and modulate dendritic cell (DC) function within the tumour, alter tumour immunotolerance inducing melanoma-specific cytotoxic T cells, cause complete remission and improve survival. GNP-LLO91-99 nanovaccines showed superior tumour regression and survival benefits, when combined with anti-PD-1 or anti-CTLA-4 checkpoint inhibitors, resulting in an improvement in the efficacy of these immunotherapies. Studies on monocyte-derived DCs from patients with stage IA, IB or IIIB melanoma confirmed the ability of GNP-LLO91-99 nanovaccines to complement the action of checkpoint inhibitors, by not only reducing the expression of cell-death markers on DCs, but also potentiating DC antigen-presentation. We propose that GNP-LLO91-99 nanovaccines function as immune stimulators and immune effectors and serve as safe cancer therapies, alone or in combination with other immunotherapies.- Published
- 2018
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48. Biocompatible single-chain polymer nanoparticles loaded with an antigen mimetic as potential anticancer vaccine.
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Gracia R, Marradi M, Salerno G, Pérez-Nicado R, Pérez-San Vicente A, Dupin D, Rodriguez J, Loinaz I, Chiodo F, and Nativi C
- Abstract
The "pancarcinoma" Tn antigen (αGalNAc-O-Ser/Thr) is a tumor-associated carbohydrate antigen (TACA) overexpressed on the surface of cancer cells and suitable target for anticancer vaccines. However, TACAs commonly show weak immunogenicity, low in vivo stability, and poor bioavailability. To address these issues, the development of physiologically stable TACA synthetic mimetics and novel nanocarriers for multivalent display are object of intense research. Nanomaterials represent suitable scaffolds to multimerize antigens, but absence of toxicity, easy functionalization and capability to incorporate biomolecules are compulsory characteristics for vaccine nanocarriers. Here, we report on the conjugation of a synthetic Tn-antigen mimetic to biocompatible and water-dispersible dextran-based single-chain nanoparticles (DXT-SCPNs). In vitro stimulation of PBMCs and analysis of interleukins production indicated a specific innate immune modulation mediated by the multivalent presentation of the Tn mimetic at the nanoparticle surface. These preliminary results pave the way for the development of Tn-mimetic clusters on biocompatible DXT-SCPN for TACA-based vaccines.
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- 2018
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49. Loading dendritic cells with gold nanoparticles (GNPs) bearing HIV-peptides and mannosides enhance HIV-specific T cell responses.
- Author
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Climent N, García I, Marradi M, Chiodo F, Miralles L, Maleno MJ, Gatell JM, García F, Penadés S, and Plana M
- Subjects
- Cell Proliferation, Cells, Cultured, Chemokines metabolism, Cytokines metabolism, Dendritic Cells drug effects, HIV Infections drug therapy, HIV Infections virology, HIV-1 drug effects, Humans, Lymphocyte Activation, Mannosides chemistry, Metal Nanoparticles chemistry, Peptide Fragments administration & dosage, Peptide Fragments immunology, Phosphoproteins immunology, T-Lymphocytes drug effects, T-Lymphocytes virology, T-Lymphocytes, Cytotoxic immunology, Viral Matrix Proteins immunology, gag Gene Products, Human Immunodeficiency Virus immunology, Dendritic Cells immunology, Gold chemistry, HIV Infections immunology, HIV-1 immunology, Metal Nanoparticles administration & dosage, Peptide Fragments pharmacology, T-Lymphocytes immunology
- Abstract
Gold nanoparticles (GNPs) decorated with glycans ameliorate dendritic cells (DC) uptake, antigen-presentation and T-cells cross-talk, which are important aspects in vaccine design. GNPs allow for high antigen loading, DC targeting, lack of toxicity and are straightforward prepared and easy to handle. The present study aimed to assess the capacity of DC to process and present HIV-1-peptides loaded onto GNPs bearing high-mannoside-type oligosaccharides (P1@HM) to autologous T-cells from HIV-1 patients. The results showed that P1@HM increased HIV-specific CD4
+ and CD8+ T-cell proliferation and induced highly functional cytokine secretion compared with HIV-peptides alone. P1@HM elicits a highly efficient secretion of pro-TH 1 cytokines and chemokines, a moderate production of pro-TH 2 and significant higher secretion of pro-inflammatory cytokines such as TNF-α and IL-1β. Thus, co-delivery of HIV-1 antigens and HM by GNPs is an excellent vaccine delivery system inducing HIV-specific cellular immune responses in HIV+ patients, being a promising approach to improve anti-HIV-1 vaccines., (Copyright © 2017 Elsevier Inc. All rights reserved.)- Published
- 2018
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50. GNP-GAPDH 1-22 nanovaccines prevent neonatal listeriosis by blocking microglial apoptosis and bacterial dissemination.
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Calderon-Gonzalez R, Frande-Cabanes E, Teran-Navarro H, Marimon JM, Freire J, Salcines-Cuevas D, Carmen Fariñas M, Onzalez-Rico C, Marradi M, Garcia I, Alkorta-Gurrutxaga M, San Nicolas-Gomez A, Castañeda-Sampedro A, Yañez-Diaz S, Penades S, Punzon C, Gomez-Roman J, Rivera F, Fresno M, and Alvarez-Dominguez C
- Abstract
Clinical cases of neonatal listeriosis are associated with brain disease and fetal loss due to complications in early or late pregnancy, which suggests that microglial function is altered. This is believed to be the first study to link microglial apoptosis with neonatal listeriosis and listeriosis-associated brain disease, and to propose a new nanovaccine formulation that reverses all effects of listeriosis and confers Listeria monocytogenes (LM)-specific immunity. We examined clinical cases of neonatal listeriosis in 2013-2015 and defined two useful prognostic immune biomarkers to design listeriosis vaccines: high anti-GAPDH
1-22 titres and tumor necrosis factor (TNF)/interleukin (IL)-6 ratios. Therefore, we developed a nanovaccine with gold glyco-nanoparticles conjugated to LM peptide 1-22 of GAPDH (Lmo2459), GNP-GAPDH1-22 nanovaccinesformulated with a pro-inflammatory Toll-like receptor 2/4-targeted adjuvant. Neonates born to non-vaccinated pregnant mice with listeriosis, showed brain and vascular diseases and significant microglial dysfunction by induction of TNF-α-mediated apoptosis. This programmed TNF-mediated suicide explains LM dissemination in brains and livers and blocks production of early pro-inflammatory cytokines such as IL-1β and interferon-α/β. In contrast, neonates born to GNP-GAPDH1-22 -vaccinated mothers before LM infection, did not develop listeriosis or brain diseases and had functional microglia. In nanovaccinated mothers, immune responses shifted towards Th1/IL-12 pro-inflammatory cytokine profiles and high production of anti-GAPDH1-22 antibodies, suggesting good induction of LM-specific memory., Competing Interests: CONFLICTS OF INTEREST The authors declare that they have no conflicts of interest with the contents of this article.- Published
- 2017
- Full Text
- View/download PDF
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