
Marco MarradiUniversity of Florence | UNIFI · Dipartimento di Chimica "Ugo Schiff"
Marco Marradi
PhD Chemistry Sciences
About
104
Publications
14,441
Reads
How we measure 'reads'
A 'read' is counted each time someone views a publication summary (such as the title, abstract, and list of authors), clicks on a figure, or views or downloads the full-text. Learn more
3,811
Citations
Introduction
The research activity of Marco Marradi is at the interface between organic chemistry and material sciences and focuses on the synthesis and characterization of ligands for the biofunctionalization of nanoparticles with the aim of solving biomedical problems.
Publications
Publications (104)
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 esta...
Modulation of N -acetylgalactosamine-6-sulfatase (GALNS) activity is a promising tool for treating metabolic disorders, neuropathic pain, and cancer. Gold nanoparticles coated with sugar and sulfated ligands were prepared and assayed for this purpose.
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 glyconanomat...
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 enz...
This study presents proof of concept assays to validate gold nanoparticles loaded with the bacterial peptide 91–99 of the listeriolysin O toxin (GNP-LLO91–99 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 f...
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 monosa...
Polyamine Phosphate Nanoparticles
In article number 2102211, Sergio Enrique Moya and co-workers present supramolecular polyamine phosphate nanoparticles (PANs) assembled from polyamines modified with polyethylene glycol (PEG) that vary size and charge depending on the number of PEG molecules per polyamine. PEGylated PANs with 10 PEG chains per poly...
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 P...
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 vir...
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 ac...
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 the investigated modifications conferred interfacial activity to produce...
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...
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 p...
Introduction
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 administrat...
This article focuses on the synthesis and applications in bioimaging, sensing and therapy of semiconductor Quantum Dots (QDs) coated with carbohydrates (glyco-QDs).
After a brief historical excursus on the discovery of semiconductor QDs, the reader will be introduced to the general characteristics of these types of nanomaterials, especially focusin...
Indium(0)‐mediated reductions have been reported for the transformation of several functional groups (imines, oximes, nitro groups, isoxazolidines, and conjugated alkenes, among others), prompted by the opportunity of performing the reactions in aqueous media and green conditions. We describe here the comparison of several reactions using indium or...
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...
Gold glyconanoparticles loaded with the listeriolysin O peptide 91–99 (GNP-LLO91-99), 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 immunoth...
Gold glyconanoparticles (Au GNPs) decorated with the natural iminosugar DAB-1 at different densities are reported. These new multivalent iminosugar architectures strongly and selectively inhibit N-acetylgalactosamine-6-sulfatase (GALNS), whose deficiency is connected to the lysosomal storage disease Morquio A. The combination of the dendrimeric tec...
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 s...
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 o...
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 nano...
Dendritic cell-based (DCs-based) vaccines are promising cancer immunotherapies. However, several factors such as the lack of efficient targeted delivery or the source and type of DCs, limited the efficacy of DCs and their clinical potential. We propose an alternative nanotechnology-based vaccine platform with bacterial prophylactic abilities that u...
Water-dispersible dextran-based single-chain polymer nanoparticles (SCPNs) were prepared in aqueous media and under mild conditions. Radiolabeling of the resulting biocompatible materials allowed the study of lung deposition of aqueous aerosols after intratracheal nebulization by means of single-photon emission computed tomography (SPECT), demonstr...
Aim:
Nanotechnology-based fully synthetic carbohydrate vaccines are promising alternatives to classic polysaccharide/protein conjugate vaccines. We have prepared gold glyco-nanoparticles (GNP) bearing two synthetic carbohydrate antigens related to serotypes 19F and 14 of Streptococcus pneumoniae and evaluated their immunogenicity in vivo.
Results...
The development of tools for the early diagnosis of pancreatic adenocarcinoma is an urgent need in order to increase treatment success rate and reduce patient mortality. Here, we present a modular nanosystem platform integrating soft nanoparticles with a targeting peptide and an active imaging agent for diagnostics. Biocompatible single-chain polym...
Listeriosis is a fatal infection for fetuses and newborns with two clinical main morbidities in the neonatal period, meningitis and diffused cutaneous lesions. In this study, we vaccinated pregnant females with two gold glyconanoparticles (GNP) loaded with two peptides, listeriolysin peptide 91–99 (LLO91–99) or glyceraldehyde-3-phosphate dehydrogen...
Submicron-sized poly(lactide-co-glycolide) nanoparticles (PLGA-NPs) stabilised with bovine serum albumin (BSA) are dual radiolabelled using gamma emitters with different energy spectra incorporated into the core and coating. PLGA core is labelled by encapsulation of
111
In-doped iron oxide NPs inside PLGA-NPs during NP preparation, while the BSA co...
A novel nanovaccine using gold glyconanoparticles conjugated with a LLO91-99 listeriolysin O peptide and formulated with Advax protect against murine listeriosis
A novel and facile method was developed to produce hybrid graphene oxide (GO)-polyelectrolyte (PE) capsules using erythrocyte cells as templates. The capsules are easily produced through the layer-by-layer technique using alternating polyelectrolyte layers and GO sheets. The amount of GO and therefore its coverage in the resulting capsules can be t...
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 α-d-mannose or β-d-glucose to modulate the density of biologically active pyrrolizidine and piperidine iminosugars at the gold surface. Exceptionally small and water dispersi...
In recent years, nanomedicine has transformed many areas of traditional medicine, and enabled fresh insights into the prevention of previously difficult to treat diseases. An example of the transformative power of nanomedicine is a recent nano-vaccine against listeriosis, a serious bacterial infection affecting not only pregnant women and their neo...
Recent advances in the preparation and characterization of metal core-based nanoparticles have opened the way to their exploration as carriers for carbohydrate-based vaccines. Here we describe the protocols for the preparation and characterization of water dispersible gold nanoparticles (1-3 nm gold diameter) as carriers for carbohydrate antigens....
The determination of nanoparticle (NP) stability and degradation in vivo is essential for the accurate evaluation of NP biodistribution in medical applications and for understanding their toxicological effects. Such determination is particularly challenging because NPs are extremely difficult to detect and quantify once distributed in a biological...
Tumor associated carbohydrate antigens Lipopolysaccharides as microbe-associated molecular patterns Carbohydrate protein interactions at the host-pathogen interface Glyconanotechnology and disease Glycodendrimers for drug discovery Chemical glycobiology of infection Glycosylated antitumor ether lipids Synthesis of novel molecules for glycobiology a...
In recent years there has been increasing evidence of the importance of carbohydrates and glycoconjugates in biomedical applications, and the use of synthetic ligands based on carbohydrates as drugs has received much attention. Focussing on drug discovery from key targets and placing an emphasis on the multi-disciplinary approaches necessary to cha...
In the search for an effective vaccine against the human pathogen, Listeria monocytogenes (Listeria), gold glyconanoparticles (GNP) loaded with a listeriolysin O peptide LLO91–99 (GNP-LLO) were used to immunise mice, initially using a dendritic cell (DC) vaccine approach, but subsequently using a standard parenteral immunisation approach. To enhanc...
The dynamic behaviour of gold nanoparticles functionalised with glucose (Glc-Au NPs) has been studied here by means of fluorescence correlation spectroscopy (FCS). Meaningful data on the state of aggregation and dynamics of Glc-Au NPs fluorescently-labelled with HiLyte Fluor647 (Glc-Au-Hi NPs) in the intracellular environment were obtained. Moreove...
The therapeutic approach for the treatment of HIV infection is based on the highly active antiretroviral therapy (HAART), a cocktail of antiretroviral drugs. Notwithstanding HAART has shown different drawbacks like toxic side effects and the emergence of viral multidrug resistance. Nanotechnology offers new tools to improve HIV drug treatment and p...
Magnetic resonance imaging (MRI) plays an important role in tumor detection/diagnosis. The use of exogenous contrast agents (CAs) helps to improve the discrimination between lesion and neighbouring tissue, but most of the currently available CAs are non-specific. Assessing the performance of new, selective CAs requires exhaustive assays and large a...
Galactofuranose (Galf) is the five-membered ring form of galactose exclusively found in non-mammalian species, amongst which several pathogens. To determine the putative role of this carbohydrate in host-pathogen interactions, we synthesized multivalent gold nanoparticles carrying Galf (Galf-GNPs) and show that they are recognized by the EB-A2 anti...
Improved detection of anti-carbohydrate antibodies is a need in clinical identification of biomarkers for cancer cells or pathogens. Here, we report a new ELISA approach for the detection of specific immunoglobulins (IgGs) against carbohydrates. Two nanometer gold glyconanoparticles bearing oligosaccharide epitopes of HIV or Streptococcus pneumonia...
Figures related to different control experiments (Figures S1-S6) described in the manuscript are available in the File S1. A comparison between the GNP-ELISA and the BSA-ELISA is reported in Figure S5 in File S1.
(DOC)
Difference in the tetramannoside loading between the 50% and the 10% TetraMan-GNPs (Text S1 in File S2) and details of purification of IgGs from mice sera (Text S2 in File S2) are also available.
(DOC)
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 affini...
Targeted magnetic resonance imaging (MRI) probes for selective cell labelling and tracking are highly desired. We here present biocompatible sugar-coated paramagnetic Gd-based gold nanoparticles (Gd-GNPs) and test them as MRI T1 reporters in different cellular lines at a high magnetic field (11.7 T). With an average number of 20 Gd atoms per nanopa...
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 quest for the construction of multivalent carbohydrate systems, with precise geometries that are highly efficient in interacting with carbohydrate binding proteins, has been a goal of synthetic chemists since the discovery of the multivalent nature of carbohydrate-mediated interactions. However, the control of the spatial and topological requir...
After nearly three decades since the discovery of human immunodeficiency virus (HIV) (1983), no effective vaccine or microbicide is available, and the virus continues to infect millions of people worldwide each year. HIV antiretroviral drugs reduce the death rate and improve the quality of life in infected patients, but they are not able to complet...
The broadly neutralizing anti-HIV-1 monoclonal antibody 2G12 targets exclusively a conserved cluster of high-mannose oligosaccharides present on the outer viral envelope glycoprotein gp120. This characteristic makes the otherwise immunogenically "silent" glycan shield of gp120 a tempting target for drug and vaccine design. However, immune responses...
The preparation of low-generation dendrimers based on a simple calix[4]arene scaffold by insertion of the iminosugar-analogue C(2)-symmetric 3,4-dihydroxypyrrolidine is described. This methodology allows a rapid incorporation of a considerable number of iminosugar-like moieties in a reduced volume and in a well-defined geometry. The inclusion of al...
The human immunodeficiency virus type-1 (HIV-1) is able to shield immunogenic peptide epitopes on its envelope spike (a trimer of two glycoproteins, gp120 and gp41) by presenting numerous host-derived N-linked glycans. Nevertheless, broadly neutralizing antibodies against gp120 and gp41 have been isolated from HIV-1-infected patients and provide pr...
Coupling of capsular polysaccharides of pathogens to immunogenic protein carriers (conjugate vaccines) improves carbohydrate immune response. Our idea is to explore gold nanoclusters as carriers to prepare fully synthetic carbohydrate vaccines.
Gold glyconanoparticles bearing a synthetic tetrasaccharide epitope related to the Streptococcus pneumoni...
Multivalent protein-carbohydrate interactions are involved in the initial stages of many fundamental biological and pathological processes through lectin-carbohydrate binding. The design of high affinity ligands is therefore necessary to study, inhibit and control the processes governed through carbohydrate recognition by their lectin receptors. Ca...