RESUMEN
Ultra-small gold nanoparticles (UAuNPs) are extremely interesting for applications in nanomedicine thanks to their good stability, biocompatibility, long circulation time and efficient clearance pathways. UAuNPs engineered with glycans (Glyco-UAuNPs) emerged as excellent platforms for many applications since the multiple copies of glycans can mimic the multivalent effect of glycoside clusters. Herein, we unravel a straightforward photo-induced synthesis of Glyco-UAuNPs based on a reliable and robust microfluidic approach. The synthesis occurs at room temperature avoiding the use of any further chemical reductant, templating agents or co-solvents. Exploiting 1 Hâ NMR spectroscopy, we showed that the amount of thiol-ligand exposed on the UAuNPs is linearly correlated to the ligand concentration in the initial mixture. The results pave the way towards the development of a programmable synthetic approach, enabling an accurate design of the engineered UAuNPs or smart hybrid nano-systems.
Asunto(s)
Nanopartículas del Metal , Nanopartículas , Oro/química , Nanopartículas del Metal/química , Microfluídica , Ligandos , Nanopartículas/química , Polisacáridos/químicaRESUMEN
Cannabidiol (CBD) is a biologically active compound present in the plants of the Cannabis family, used as anticonvulsant, anti-inflammatory, anti-anxiety, and more recently, anticancer drug. In this work, its use as a new self-assembly inducer in the formation of nanoparticles is validated. The target conjugates are characterized by the presence of different anticancer drugs (namely N-desacetyl thiocolchicine, podophyllotoxin, and paclitaxel) connected to CBD through a linker able to improve drug release. These nanoparticles are formed via solvent displacement method, resulting in monodisperse and stable structures having hydrodynamic diameters ranging from 160 to 400 nm. Their biological activity is evaluated on three human tumor cell lines (MSTO-211H, HT-29, and HepG2), obtaining GI50 values in the low micromolar range. Further biological assays were carried out on MSTO-211H cells for the most effective NP 8B, confirming the involvement of paclitaxel in cytotoxicity and cell death mechanism.
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Antineoplásicos , Cannabidiol , Nanopartículas , Humanos , Cannabidiol/farmacología , Antineoplásicos/farmacología , Paclitaxel/farmacología , Paclitaxel/química , Línea Celular TumoralRESUMEN
The increased phenomenon of antimicrobial resistance and the slow pace of development of new antibiotics are at the base of a global health concern regarding microbial infections. Antibiotic resistance kills an estimated 700,000 people each year worldwide, and this number is expected to increase dramatically if efforts are not made to develop new drugs or alternative containment strategies. Increased vaccination coverage, improved sanitation or sustained implementation of infection control measures are among the possible areas of action. Indeed, vaccination is one of the most effective tools of preventing infections. Starting from 1970s polysaccharide-based vaccines against Meningococcus, Pneumococcus and Haemophilus influenzae type b have been licensed, and provided effective protection for population. However, the development of safe and effective vaccines for infectious diseases with broad coverage remains a major challenge in global public health. In this scenario, nanosystems are receiving attention as alternative delivery systems to improve vaccine efficacy and immunogenicity. In this report, we provide an overview of current applications of glyconanomaterials as alternative platforms in the development of new vaccine candidates. In particular, we will focus on nanoparticle platforms, used to induce the activation of the immune system through the multivalent-displacement of saccharide antigens.
Asunto(s)
Bacterias/efectos de los fármacos , Glicoconjugados/química , Glicoconjugados/farmacología , Nanopartículas/química , Animales , Farmacorresistencia BacterianaRESUMEN
A small set of trehalose-centered putative autophagy inducers was rationally designed and synthesized, with the aim to identify more potent and bioavailable autophagy inducers than free trehalose, and to acquire information about their molecular mechanism of action. Several robust, high yield routes to key trehalose intermediates and small molecule prodrugs (2-5), putative probes (6-10) and inorganic nanovectors (12a - thiol-PEG-triazole-trehalose constructs 11) were successfully executed, and compounds were tested for their autophagy-inducing properties. While small molecules 2-11 showed no pro-autophagic behavior at sub-millimolar concentrations, trehalose-bearing PEG-AuNPs 12a caused measurable autophagy induction at an estimated 40 µM trehalose concentration without any significant toxicity at the same concentration.
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Autofagia/efectos de los fármacos , Fármacos Neuroprotectores/farmacología , Trehalosa/análogos & derivados , Trehalosa/farmacología , Diseño de Fármacos , Oro/química , Oro/toxicidad , Células HeLa , Humanos , Nanopartículas del Metal/química , Nanopartículas del Metal/toxicidad , Fármacos Neuroprotectores/síntesis química , Fármacos Neuroprotectores/toxicidad , Polietilenglicoles/química , Polietilenglicoles/toxicidad , Trehalosa/toxicidadRESUMEN
The development of novel delivery systems capable of enhancing the antibody binding affinity and immunoactivity of short length saccharide antigens is at the forefront of modern medicine. In this regard, gold nanoparticles (AuNPs) raised great interest as promising nano-vaccine platform, as they do not interfere with the desired immune response and their surface can be easily functionalized, enabling the antigen multivalent presentation. In addition, the nanoparticles morphology can have a great impact on their biological properties. Gram-positive Group A Streptococcus (GAS) is a bacterium responsible for many infections and represents a priority healthcare concern, but a universal vaccine is still unavailable. Since all the GAS strains have a cell wall characterized by a common polyrhamnose backbone, this can be employed as alternative antigen to develop an anti-GAS vaccine. Herein, we present the synthesis of two oligorhamnoside fragments and their corresponding oligorhamnoside-AuNPs, designed with two different morphologies. By competitive ELISA we assessed that both symmetric and anisotropic oligorhamnan nanoparticles inhibit the binding of specific polyclonal serum much better than the unconjugated oligosaccharides.
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Anticuerpos/inmunología , Oro/química , Nanopartículas del Metal/química , Oligorribonucleótidos/inmunología , Streptococcus/química , Anticuerpos/química , Conformación de Carbohidratos , Oro/inmunología , Oligorribonucleótidos/síntesis química , Oligorribonucleótidos/química , Streptococcus/inmunologíaRESUMEN
Since their discovery, therapeutic or prophylactic vaccines represent a promising option to prevent or cure infections and other pathologies, such as cancer or autoimmune disorders. More recently, among a number of nanomaterials, gold nanoparticles (AuNPs) have emerged as novel tools for vaccine developments, thanks to their inherent ability to tune and upregulate immune response. Moreover, owing to their features, AuNPs can exert optimal actions both as delivery systems and as adjuvants. Notwithstanding the potential huge impact in vaccinology, some challenges remain before AuNPs in vaccine formulations can be translated into the clinic. The current review provides an updated overview of the most recent and effective application of gold nanoparticles as efficient means to develop a new generation of vaccine.
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Nanopartículas del Metal , Vacunas , Adyuvantes Inmunológicos , Oro , Desarrollo de VacunasRESUMEN
Congenital prepubic sinus is a very rare urogenital anomaly that manifests as a tubular structure of varying histological findings that drains to the skin overlying the pubic symphysis. This tract has been observed to course above, below or, in only a handful of cases, directly through the pubis. We report a case of congenital prepubic sinus with this unusual transpubic course in an 18-year-old man. The patient was initially taken to the operating room for excision of a presumed inclusion cyst. At the time of surgery, the collection was found to track proximally and was excised down to the level of the pubic symphysis. Subsequent magnetic resonance (MR) imaging established the diagnosis of congenital prepubic sinus. We describe the different anatomical courses of congenital prepubic sinus, hypotheses of its pathogenesis, and the use of MR imaging in both diagnosis and surgical planning.
Asunto(s)
Fístula Cutánea/diagnóstico por imagen , Imagen por Resonancia Magnética , Sínfisis Pubiana/anomalías , Anomalías Urogenitales/diagnóstico por imagen , Adolescente , Fístula Cutánea/cirugía , Humanos , Masculino , Anomalías Urogenitales/cirugíaRESUMEN
BACKGROUND: The increasing use of gold nanoparticles (AuNPs) in the field of neuroscience instilled hope for their rapid translation to the clinical practice. AuNPs can be engineered to carry therapeutics or diagnostics in the diseased brain, possibly providing greater cell specificity and low toxicity. Although there is a general enthusiasm for these tools, we are in early stages of their development. Overall, their brain penetrance, stability and cell specificity are critical issues that must be addressed to drive AuNPs to the clinic. RESULTS: We studied the kinetic, distribution and stability of PEG-coated AuNPs in mice receiving a single injection into the cisterna magna of the 4th ventricle. AuNPs were conjugated with the fluorescent tag Cy5.5 (Cy5.5-AuNPs) to track their in vivo distribution. Fluorescence levels from such particles were detected in mice for weeks. In situ analysis of brains by immunofluorescence and electron microscopy revealed that Cy5.5-AuNPs penetrated the brain parenchyma, spreading in the CNS parenchyma beneath the 4th ventricle. Cy5.5-AuNPs were preferentially found in neurons, although a subset of resting microglia also entrapped these particles. CONCLUSIONS: Our results suggest that the ICM route for delivering gold particles allows the targeting of neurons. This approach might be pursued to carry therapeutics or diagnostics inside a diseased brain with a surgical procedure that is largely used in gene therapy approaches. Furthermore, this approach could be used for radiotherapy, enhancing the agent's efficacy to kill brain cancer cells.
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Encéfalo/metabolismo , Oro/química , Nanopartículas del Metal/química , Polietilenglicoles/química , Animales , Carbocianinas/química , Línea Celular , Supervivencia Celular/efectos de los fármacos , Cisterna Magna , Estabilidad de Medicamentos , Colorantes Fluorescentes/química , Humanos , Ratones , Neuronas/citología , Neuronas/efectos de los fármacos , Permeabilidad , Distribución TisularRESUMEN
Gold nanoparticles (AuNPs) play a crucial role in the development of nanomedicine, principally due to their unique photophysical properties and high biocompatibility. The possibility to tune and customize the localized surface plasmon resonance (LSPR) toward near-infrared region by modulating the AuNP shape is one of the reasons for the huge widespread use of AuNPs. The controlled synthesis of no-symmetrical nanoparticles, named anisotropic, is an exciting goal achieved by the scientific community which explains the exponential increase of the number of publications related to the synthesis and use of such type of AuNPs. Even with such steps forward and the AuNP translation in clinic being done, some key issues are still remain and they are related to a reliable and scalable production, a full characterization, and to the development of nanotoxicology studies on the long run. In this review we highlight the very recent advances on the synthesis of the main classes of anisotropic AuNPs (nanorods, nanourchins and nanocages) and their use in the biomedical fields, in terms of diagnosis and therapeutics.
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Oro/química , Oro/uso terapéutico , Nanopartículas del Metal/química , Nanopartículas del Metal/uso terapéutico , Nanomedicina/métodos , Animales , Anisotropía , Humanos , Nanopartículas del Metal/ultraestructura , Nanotecnología/métodosRESUMEN
Star-shaped gold nanoparticles (StarAuNPs) are extremely attractive nanomaterials, characterized by localized surface plasmon resonance which could be potentially employed in a large number of applications. However, the lack of a reliable and reproducible synthetic protocols for the production of StarAuNPs is the major limitation to their spreading. For the first time, here we present a robust protocol to manufacture reproducible StarAuNPs by exploiting a fluidic approach. Star-shaped AuNPs have been synthesized by means of a seed-less protocol, employing ascorbic acid as reducing agent at room temperature. Moreover, the versatility of the bench-top microfluidic protocol has been exploited to afford hydrophilic, hydrophobic and solid-supported engineered StarAuNPs, by avoiding intermediate NP purifications.
RESUMEN
Glyco-gold nanoparticles combine in a single entity the peculiar properties of gold nanoparticles with the biological activity of carbohydrates. The result is an exciting nanosystem, able to mimic the natural multivalent presentation of saccharide moieties and to exploit the peculiar optical properties of the metallic core. In this review, we present recent advances on glyco-gold nanoparticle applications in different biological fields, highlighting the key parameters which inspire the glyco nanoparticle design.
RESUMEN
Hetero-nanoparticles represent an important family of composite nanomaterials that in the past years are attracting ever-growing interest. Here, we report a new strategy for the synthesis of water dispersible cobalt ferrite nanoparticles (CoxFe3-xO4 NPs) decorated with ultrasmall (2-3 nm) gold nanoparticles (Au NPs). The synthetic procedure is based on the use of 2,3-meso-dimercaptosuccinic acid (DMSA), which plays a double role. First, it transfers cobalt ferrite NPs from the organic phase to aqueous media. Second, the DMSA reductive power promotes the in situ nucleation of gold NPs in proximity of the magnetic NP surface. Following this procedure, we achieved a water dispersible nanosystem (CoxFe3-xO4-DMSA-Au NPs) which combines the cobalt ferrite magnetic properties with the catalytic features of ultrasmall Au NPs. We showed that CoxFe3-xO4-DMSA-Au NPs act as an efficient nanocatalyst to reduce 4-nitrophenol to 4-aminophenol and that they can be magnetically recovered and recycled. It is noteworthy that such nanosystem is more catalytically active than Au NPs with equal size. Finally, a complete structural and chemical characterization of the hetero-NPs is provided.
RESUMEN
Au- and iron-based magnetic nanoparticles (NPs) are promising NPs for biomedical applications due to their unique properties. The combination of a gold coating over a magnetic core puts together the benefits from adding the magnetic properties to the robust chemistry provided by the thiol functionalization of gold. Here, the use of Au-coated magnetic NPs for molecular detection of a single methylation in DNA aptamer is described. Binding of α-thrombin to two aptamers conjugated to these NPs causes aggregation, a phenomenon that can be observed by UV, DLS and MRI. These techniques discriminate a single methylation in one of the aptamers, preventing aggregation due to the inability of α-thrombin to recognize it. A parallel study with gold and ferromagnetic NPs is detailed, concluding that the Au coating of FexOy NP does not affect their performance and that they are suitable as complex biosensors. These results prove the high detection potency of Au-coated SPIONs for biomedical applications especially for DNA repair detection.
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Aptámeros de Nucleótidos/química , Técnicas Biosensibles , Oro , Nanopartículas del Metal , Aptámeros de Nucleótidos/metabolismo , Reparación del ADN , Compuestos Férricos/química , Oro/química , Humanos , Imagen por Resonancia Magnética , Nanopartículas del Metal/química , Nanopartículas del Metal/ultraestructura , Unión Proteica , Trombina/metabolismoRESUMEN
Mannose-binding lectin (MBL) activates the complement system lectin pathway and subsequent inflammatory mechanisms. The incidence and outcome of many human diseases, such as brain ischemia and infections, are associated with and influenced by the activity and serum concentrations of MBL in body fluids. To quantify MBL levels, tests based on ELISA are used, requiring several incubation and washing steps and lengthy turnaround times. Here, we aimed to develop a nanoplasmonic assay for direct MBL detection in human serum at the point of care. Our assay is based on gold nanorods (GNRs) functionalized with mannose (Man-GNRs) via an amphiphilic linker. We experimentally determined the effective amount of sugar linked to the nanorods' surface, resulting in an approximate grafting density of 4 molecules per nm2, and an average number of 11 to 13 MBL molecules binding to a single nanoparticle. The optimal Man-GNRs concentration to achieve the highest sensitivity in MBL detection was 15 µg·mL-1. The specificity of the assay for MBL detection both in simple buffer and in complex pooled human sera was confirmed. Our label-free biosensor is able to detect MBL concentrations as low as 160 ng·mL-1 within 15 min directly in human serum via a one-step reaction and by using a microplate reader. Hence, it forms the basis for a fast, noninvasive, point-of-care assay for diagnostic indications and monitoring of disease and therapy.
Asunto(s)
Técnicas Biosensibles , Oro , Lectina de Unión a Manosa , Sistemas de Atención de Punto , Humanos , Oro/química , Lectina de Unión a Manosa/sangre , Lectina de Unión a Manosa/química , Técnicas Biosensibles/métodos , Nanotubos/química , Manosa/química , Manosa/sangre , Nanopartículas del Metal/químicaRESUMEN
The reversibility of the covalent interaction between boronic acids and 1,2- or 1,3-diols has put the spotlight on this reaction for its potential in the development of sensors and for the fishing of bioactive glycoconjugates. In this work, we describe the investigation of this reaction for the reversible functionalization of the surface of CdSe/ZnS Quantum Rods (QRs). With this in mind, we have designed a turn-off Förster resonance energy transfer (FRET) system that ensures monitoring the extent of the reaction between the phenyl boronic residue at the meso position of a BODIPY probe and the solvent-exposed 1,2-diols on QRs' surface. The reversibility of the corresponding boronate ester under oxidant conditions has also been assessed, thus envisioning the potential sensing ability of this system.
RESUMEN
A hybrid cellulose-based programmable nanoplatform for applications in precision radiation oncology is described. Here, sugar heads work as tumor targeting moieties and steer the precise delivery of radiosensitizers, i.e. gold nanoparticles (AuNPs) into triple negative breast cancer (TNBC) cells. This "Trojan horse" approach promotes a specific and massive accumulation of radiosensitizers in TNBC cells, thus avoiding the fast turnover of small-sized AuNPs and the need for high doses of AuNPs for treatment. Application of X-rays resulted in a significant increase of the therapeutic effect while delivering the same dose, showing the possibility to use roughly half dose of X-rays to obtain the same radiotoxicity effect. These data suggest that this hybrid nanoplatform acts as a promising tool for applications in enhancing cancer radiotherapy effects with lower doses of X-rays.
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Celulosa , Oro , Nanopartículas del Metal , Fármacos Sensibilizantes a Radiaciones , Neoplasias de la Mama Triple Negativas , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Fármacos Sensibilizantes a Radiaciones/química , Oro/química , Celulosa/química , Humanos , Nanopartículas del Metal/química , Nanopartículas del Metal/uso terapéutico , Nanopartículas del Metal/efectos de la radiación , Línea Celular Tumoral , Femenino , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Nanopartículas/química , Supervivencia Celular/efectos de los fármacosRESUMEN
Pseudo-oligosaccharides have attracted much interest as scaffolds for the synthesis of sugar mimics endowed with very similar biological properties but structurally and synthetically simpler than their natural counterparts. Herein, the synthesis of pseudo-oligosaccharides using the cross-metathesis reaction between distinct sugar-olefins followed by intramolecular selenocyclization of the obtained heterodimer as key steps is first investigated. This methodology has been then applied to the preparation of structural analogues of the trisaccharide repeating unit from Streptococcus pneumoniae 19F. The inhibition abilities of the synthetic molecules were evaluated by a competitive ELISA assay using a rabbit polyclonal anti-19F serum.
Asunto(s)
Compuestos de Organoselenio/química , Polisacáridos/síntesis química , Streptococcus pneumoniae/química , Ciclización , Estructura Molecular , Polisacáridos/químicaRESUMEN
Our group recently proposed an innovative sustainable reductant-adsorbent material, tin(II)-hydroxyapatite (Sn/HAP, ca. 10 wt% Sn) for the interfacial Cr(VI) reductive adsorption process. In this study, Cr(VI) removal capacity was evaluated in multi-component solutions containing representative background ions (i.e., CaCl2, Ca(NO3)2, MgSO4, Na2SO4, Fe(NO3)3, AlCl3, Zn(NO3)2, or Mn(NO3)2). Sn/HAP was able to reduce Cr(VI) with complete Cr3+ adsorption on HAP surface, except in the presence of Fe3+ and Al3+ ions. Some metal ions co-existing in solution, such as Fe3+, Al3+, Zn2+, and Mn2+, were also adsorbed on HAP surface. Reuse experiments of the Sn/HAP sample, up to 7 runs, resulted in a total amount of reduced Cr(VI) of ca. 15-18 mg g-1. Fast kinetics of Cr(VI) reductive adsorption at 25 °C in a multi-metal component solution was observed. The pseudo-second order model was in excellent agreement with the experimental kinetic data, leading to a rate constant (k25°C) value of ca. 30 M-1 s-1. The collection of adsorption isotherms of Cr3+ and Fe3+, together with TEM-EDX analysis permitted the unveiling of competitive adsorption phenomena between metal ions. The obtained results demonstrate that Sn/HAP could be an efficient material for the removal of hexavalent chromium in aqueous solutions containing high concentrations of inorganic impurities.
RESUMEN
Evidence collected to date by our group has demonstrated that tin(II)-functionalized hydroxyapatites (Sn/HAP) are a newly discovered class of ecofriendly reductive adsorbents for Cr(VI) removal from wastewaters. In this work an upgraded series of Sn/HAP materials assured a maximum removal capacity of ≈ 20 mgCr/g, doubling the previously reported value for Sn/HAP materials, thanks to higher Sn-dispersion as proved by X-ray photoelectron spectroscopy and electron microscopy. Insights on kinetics and thermodynamics of the reductive adsorption process are provided and the influence of pH, dosage, and nature of Cr(VI) precursors on chromium removal performances have been investigated. Pseudo-second-order kinetics described the interfacial reductive adsorption process on Sn/HAP, characterized by low activation energy (21 kJ mol-1), when measured in the 278-318 K range. Tests performed in the 2-6 pH interval showed similar efficiency in terms of Cr(VI) removal. Conventional procedures of recycling and regeneration resulted ineffective in restoring the pristine performances of the samples due to surface presence of both Sn(IV) and Cr(III). To overcome these weaknesses, the used samples (Sn + Cr/HAP) were upcycled into catalysts in a circular economy perspective. Used samples were tested as catalysts in gas-phase catalytic processes for air pollution remediation: selective catalytic reduction of NOx (NH3-SCR), NH3 selective catalytic Oxidation (NH3-SCO), and selective catalytic oxidation of methane to CO2. Catalytic tests enlightened the interesting activity of the upcycled Sn + Cr/HAP samples in catalytic oxidation processes, being able to selectively oxidize methane to CO2 at relatively low temperature.