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We describe a mild, ecofriendly, and straightforward two-step strategy for making core-shell Au@Ag bimetallic nanoparticles (BMNPs) for antibacterial nanomedicine and SERS imaging. The synthesis exploits the unique properties of the cationic polymeric cyclodextrin (PolyCD) as both reducing and stabilizing agent to obtain, monodispersed and stable Au@Ag BMNPs. PolyCD-driven protocol includes the synthesis of PolyCD-coated Au monometallic nanoparticles (MNPs) as a seed material for the subsequent growing of a silver shell. PolyCD was produced by polymerization of the azido modified βCD monomers with epichlorohydrin and subsequent reduction of azido derivative. The amino groups, as hydrochloride salts (one for CD ring), are pivotal for the formation of BMNPs in mild conditions. Nanoantibiotics and SERS-nanoTag were prepared by complexation of Au@Ag BMNPs with Linezolid (Lz) and 4-mercaptophenyl boronic acid, respectively. Au@Ag@Lz complexes showed a good antibacterial activity against all tested microorganisms including the methicillin resistant Staphylococcus aureus (MRSA).

The incorporation of gold nanoparticles (Au NPs) on graphene (G) is as valuable strategy to produce plasmonic effects that lead to the enhancement of optical absorption, resulting in improved performance of optoelectronic devices. The decoration of G layers by direct reduction of Au3+ to Au NPs using the chemical functionalities on G surface is preferred since it can result in a huge number of interactions stabilizing Au NPs. The combination of G with polymeric matrices able to act as reducing and capping agents is a successful strategy to achieve this objective. Herein, we demonstrate that both a polymeric cationic cyclodextrin (PolyCD) and the cyclodextrin units grafted on graphene layers (GCD) can be bridged, in a supramolecular assembly, through the new synthesized pegylated bis-adamantane carboxamide (BisAda) that acts as a “guest bridge”. Moreover, the cyclodextrin functionalities, such as hydroxyl groups, amino groups, hemiacetal groups, act as reductant and stabilizer for the synthesis of Au NPs in an eco-friendly way, alternative to the traditional chemical-reducing methods. Accordingly, the PolyCD@Bis-Ada@GCD assembly was decorated in situ with Au NPs by simple addition of PolyCD@BisAda@GCD to a boiling aqueous solution of Tetrachloro-auric(III) acid.

Graphene-based materials are intriguing nanomaterials with applications ranging from nanotechnology-related devices to drug delivery systems and biosensing. Multifunctional graphene platforms were proposed for the detection of several typical biomarkers (i.e., circulating tumor cells, exosomes, circulating nucleic acids, etc.) in liquid biopsy, and numerous methods, including optical, electrochemical, surface-enhanced Raman scattering (SERS), etc., have been developed for their detection. Due to the massive advancements in biology, material chemistry, and analytical technology, it is necessary to review the progress in this field from both medical and chemical sides. Liquid biopsy is considered a revolutionary technique that is opening unexpected perspectives in the early diagnosis and, in therapy monitoring, severe diseases, including cancer, metabolic syndrome, autoimmune, and neurodegenerative disorders. Although nanotechnology based on graphene has been poorly applied for the rapid diagnosis of viral diseases, the extraordinary properties of graphene (i.e., high electronic conductivity, large specific area, and surface functionalization) can be also exploited for the diagnosis of emerging viral diseases, such as the coronavirus disease 2019 (COVID-19). This review aimed to provide a comprehensive and in-depth summarization of the contribution of graphene-based nanomaterials in liquid biopsy, discussing the remaining challenges and the future trend; moreover, the paper gave the first look at the potentiality of graphene in COVID-19 diagnosis.

The occurrence of new pandemic viruses, such as SARS-CoV-1 (2003), MERS-CoV (2012) and SARS-CoV-2 (2019) has indicated an urgent need for diagnostic tools able to reliably identify infected individuals and to determine if the infection is in the acute phase. Although nanotechnology based on graphene has been poorly applied for the rapid diagnosis of viral diseases, the extraordinary properties of graphene have been recently exploited for the diagnosis of COVID-19. Novelgraphene-based field-effect transistor (GFET)biosensors were developed for the quantitative detection of viral RNA and viral spike protein.The fabrication of COVID-19 FET sensor for spike protein recognition is based on the integration of the SARS-CoV-2 spike antibody with graphene, whereas the GFET sensor for viral RNA recognition exploited the CRISPR/Cas biotechnology.

It is well known that amphiphilic cationic beta-cyclodextrins (am beta CDs) form nanovesicles able to release their cargo in aqueous solution upon applying different stimuli. In addition they can be selectively positioned onto substrates by unconventional soft lithography. This makes them a powerful tool for designing environments where different cues can be externally supplied to the cells helping to achieve good control of their fate. Lithographically controlled wetting (LCW) of am beta CD nanovesicles loaded with fluorescein isothiocyanate (FITC), am beta CD/FITC, has been used here to fabricate geometrically functionalized surfaces, thus achieving multiscale control of the cell environment. The am beta CD functionalization was strongly influenced by the surface energy of the underlying substrates that, according to their hydrophobicity, orient the am beta CD in a different way, thus "offering" different portions to the cells. The structure of the pattern was characterized both over large scales exploiting the FITC fluorescence and at the nanoscale by atomic force microscopy. Cell guidance and aCD/FITC cell internalization were demonstrated in human neuroblastoma SHSY5Y cells.

A series of polymeric silver(I) complexes with Schiff base ligands containing pyridine and 3,5-halogen substituted phenol moieties were synthesized and characterized by spectroscopic methods and in the case of Ag6 also by X-ray crystallography. All silver(I) complexes (Ag1-Ag8) were evaluated for their biological activity against a panel of pathogens including the protozoa Trypanosoma cruzi, T. brucei, T. rhodesiense and Leishmania infantum; the bacteria Staphylococcus aureus, Escherichia coli, Mycobacterium tuberculosis H37Ra and the yeast Candida albicans. Cytotoxicity evaluation was carried out on human lung fibroblasts (MRC-5) and on primary peritoneal mouse macrophages. The most relevant result reveals antileishmanial activity potential with all complexes demonstrating higher potency than the reference drug miltefosine. Complexes with the best antiprotozoal profile (i.e., Ag2 and Ag7) were selected for incorporation into poly (lactic acid) nanoparticles (PLA NPs) with the aim to enhance selectivity. PLA/Ag2 NPs and PLA/Ag7 NPs exhibited adequate physicochemical properties, that is, average size of 263 +/- 60 nm and 225 +/- 6 nm, respectively, good entrapment efficiency (69% and 63%), loading content (6.2% and 5.7%) and stability. The cytotoxicity of PLA/Ag2 NPs and PLA/Ag7 NPs on MRC-5 cells was reduced with respect to the "free" metal complexes by similar to 2-fold and similar to 6-fold, respectively.

Injectable nanobioplatforms capable of locally fighting the inflammation in osteoarticular diseases, by reducing the number of administrations and prolonging the therapeutic effect is highly challenging. &beta, Cyclodextrin cationic polymers are promising cartilage-penetrating candidates by intra-articular injection due to the high biocompatibility and ability to entrap multiple therapeutic and diagnostic agents, thus monitoring and mitigating inflammation. In this study, nanoassemblies based on poly-&beta, amino-cyclodextrin (PolyCD) loaded with the non-steroidal anti-inflammatory drug diclofenac (DCF) and linked by supramolecular interactions with a fluorescent probe (adamantanyl-Rhodamine conjugate, Ada-Rhod) were developed to manage inflammation in osteoarticular diseases. PolyCD@Ada-Rhod/DCF supramolecular nanoassemblies were characterized by complementary spectroscopic techniques including UV-Vis, steady-state and time-resolved fluorescence, DLS and &zeta, potential measurement. Stability and DCF release kinetics were investigated in medium mimicking the physiological conditions to ensure control over time and efficacy. Biological experiments evidenced the efficient cellular internalization of PolyCD@Ada-Rhod/DCF (within two hours) without significant cytotoxicity in primary human bone marrow-derived mesenchymal stromal cells (hMSCs). Finally, polyCD@Ada-Rhod/DCF significantly suppressed IL-1&beta, production in hMSCs, revealing the anti-inflammatory properties of these nanoassemblies. With these premises, this study might open novel routes to exploit original CD-based nanobiomaterials for the treatment of osteoarticular diseases.

In the framework of our studies dealing with the development of new platforms for the delivery of antiviral agents, we exploited the covalent approach based on click chemistry to link β-cyclodextrin (CD) on hyaluronic acid backbone (HA). The physico-chemical properties in terms of size, surface charge, interaction with acyclovir (Acy), selected as a model antiviral drug, have been investigated. The release profile and the biological properties (cytotoxicity and inhibition of viral plaque formation) of HA-CD/Acy complex pointed out a good antiviral activity together with a delayed-release of Acy from HA-CD/Acy.

Osteoarthritis is one of the most widespread diseases worldwide, with a progressive damage to cartilage and bone. In this context, the choice of biocompatible materials mimicking the cellular microenvironment is of the utmost importance to develop new drug carriers. Cyclodextrins (CDs) and hyaluronic acid (HA) are promising candidates for intra-articular injection in the joint synovial fluid because of the high biocompatibility and effectiveness of HA, empowered by the presence of the CD units able to entrap therapeutic agents for the regenerative process. Nano and micro scale polymeric assemblies based on cationic ?-CD polymers (PolyCDNH3+ or PolyCDNR3+) and HA have been developed by using both supramolecular and/or covalent approaches. Supramolecular nanoassemblies made from PolyCDNH3+ were obtained by using a crosslinker bearing two terminal adamantane moieties. Spongy hydrogels based on PolyCDNR3+/HA were prepared through amide formation. The nanoassemblies were loaded with fluorescent probe, with diclofenac and were characterized by complementary spectroscopic techniques including 1H-NMR, UV-Vis, steady-state and time-resolved fluorescence, DLS and ?-potential measurement. Release profiles were investigated in vitro in media mimicking the physiological conditions to ensure control over time and efficacy. Biocompatibility studies were performed by placing primary human bone marrow-derived mesenchymal stromal cells in contact with the nanosystems and testing cell viability by WST-1 assay. With these premises, this study might open novel routes to exploit original CD-based nanobiomaterials for OA treatment.

The ability of multiwalled carbon nanotubes (MWCNTs) covalently functionalized with polyamine chains of different length (ethylenediamine, EDA and tetraethylenepentamine, EPA) to induce the J-aggregation of meso-tetrakis(4-sulfonatophenyl)porphyrin (TPPS) was investigated in different experimental conditions. Under mild acidic conditions, protonated amino groups allow for the assembly by electrostatic interaction with the diacid form of TPPS, leading to hybrid nanomaterials. The presence of only one pendant amino group for a chain in EDA does not lead to any aggregation, whereas EPA (with four amine groups for chain) is effective in inducing J-aggregation using different mixing protocols. These nanohybrids have been characterized through UV/Vis extinction, fluorescence emission, resonance light scattering and circular dichroism spectroscopy. Their morphology and chemical composition have been elucidated through transmission electron microscopy (TEM) and scanning transmission electron microscopy (STEM). TEM and STEM analysis evidence single or bundles of MWCNTs in contact with TPPS J-aggregates nanotubes. The nanohybrids are quite stable for days, even in aqueous solutions mimicking physiological medium (NaCl 0.15 M). This property, together with their peculiar optical features in the therapeutic window of visible spectrum, make them potentially useful for biomedical applications.

In the past few years, extensive research has been done to develop proper drug delivery platforms that can deliver therapeutic agents to specific sites of the body or targeted cells, minimizing side effects. Similar to the microenvironment of soft tissues, hydrogels are a novel type of delivery platform with a 3D interconnected structure formed by physically or chemically cross-linked polymer networks. Drugs can be incorporated in the tridimensional scaffold and successfully vehiculated/administered into specific sites of the organism1. Hyaluronic acid (HA) is a high molecular weight negatively charged polysaccharide composed of repeating disaccharide units, which is abundant in the synovial fluid and extracellular matrix, but has also been found intracellularly. HA is involved in several biological processes such as the maintenance of the viscoelasticity of connective fluids, tissue hydration, morphogenesis and cell repair2. For these reasons it represents a valid biomaterial for tissue engineering as component of hydrogel platforms, thanks further to its good biocompatibility, biodegradability and non-immunogenicity. Currently, we are exploring the best experimental conditions to obtain a hydrogel scaffold formed by the interactions between an amphiphilic network (HA-TDA) and a cationic cyclodextrin polymer (Poly-CD). Once formed, the construct can potentially incorporate various therapeutic cargos (i.e. drugs, growth factors, exosomes, cell adhesion promoters) and diagnostic probes (i.e. fluorophores and magnetic nanoparticles), to be used as cell-laden material for bioprinting in regenerative medicine applications3. HA-TDA was synthesized by coupling of hydrophobic tetradecylamine (TDA) to hyaluronic acid (HA) in the presence of 2-chloro-4,6-dimethoxy-2,3,5-triazine (CDMT) and N-methylmorpholine (NMM). Complementary spectroscopic techniques such as UV-Vis, steady-state and time-resolved fluorescence, DLS and z-potential measurement have been used to investigate the interactions and to monitor the assembly between HA-TDA and Poly-CD at different mass ratios and the entrapment capability of HA@CD assembly.

Assemblies of Hyaluronic Acid (HA) are interesting platforms for the entrapping of drugs, growth factors, exosomes, cell adhesion promoters and diagnostic probes. They can be employed as cell-laden materials for bioprinting in regenerative medicine. Herein we explore the best experimental conditions to form hydrogel scaffolds by supramolecular interactions between polymeric networks (i.e modified HAs and cationic cyclodextrin polymer) with or without suitable crosslinking agents.