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1.
ACS Appl Mater Interfaces ; 16(23): 30556-30566, 2024 Jun 12.
Artículo en Inglés | MEDLINE | ID: mdl-38806166

RESUMEN

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/química
2.
Nanomaterials (Basel) ; 12(22)2022 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-36432299

RESUMEN

Cyclic arginyl-glycyl-aspartic acid peptide (cRGD) peptides show a high affinity towards αVß3 integrin, a receptor overexpressed in many cancers. We aimed to combine the versatility of ultrasmall gold nanoparticles (usGNP) with the target selectivity of cRGD peptide for the directed delivery of a cytotoxic payload in a novel design. usGNPs were synthesized with a modified Brust-Schiffrin method and functionalized via amide coupling and ligand exchange and their uptake, intracellular trafficking, and toxicity were characterized. Our cRGD functionalized usGNPs demonstrated increased cellular uptake by αVß3 integrin expressing cells, are internalized via clathrin-dependent endocytosis, accumulated in the lysosomes, and when loaded with mertansine led to increased cytotoxicity. Targeting via cRGD functionalization provides a mechanism to improve the efficacy, tolerability, and retention of therapeutic GNPs.

3.
Bioconjug Chem ; 30(3): 703-713, 2019 03 20.
Artículo en Inglés | MEDLINE | ID: mdl-30582799

RESUMEN

Hepatocellular carcinoma (HCC) is the sixth most common cancer worldwide with poor prognosis and limited options for treatment. Life expectancy after diagnosis is short; the currently available treatments are not well tolerated and have limited clinical benefit. There is a clear unmet clinical need for the development of new treatments. In this study, ultrasmall, 2 nm gold core nanoparticles (MidaCore) conjugated with the potent maytansine analogue DM1 (MTC-100038) were assessed as a systemic nanomedicine for the treatment of hepatocellular carcinoma. The platform improved overall tolerability of DM1, permitting ∼3-fold higher levels of drug to be administered compared to free drug. Dose for dose, MTC-100038 also facilitated delivery of ∼2.0-fold higher ( p = 0.039) levels of DM1 to the tumor compared to free DM1. MTC-100038 produced significant efficacy (tumor growth index ∼102%; p = <0.0001), in several murine xenograft models of HCC, and was superior to both free DM1 and the current standard of care, sorafenib. Furthermore, MTC-100038 displayed potent (nM) in vitro activity in various HCC primary patient derived cell lines and across various other different cancer cell types. These data demonstrate the potential of MidaCore nanoparticles to enhance tumor delivery of cytotoxic drugs and indicate MTC-100038 is worthy of further investigation as a potential treatment for HCC and other cancer types.


Asunto(s)
Antineoplásicos Fitogénicos/administración & dosificación , Carcinoma Hepatocelular/tratamiento farmacológico , Oro/química , Neoplasias Hepáticas/tratamiento farmacológico , Maitansina/administración & dosificación , Nanopartículas del Metal/química , Animales , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/farmacocinética , Línea Celular Tumoral , Modelos Animales de Enfermedad , Portadores de Fármacos , Femenino , Humanos , Maitansina/análogos & derivados , Nanopartículas del Metal/toxicidad , Ratones , Ratones Endogámicos BALB C , Tamaño de la Partícula , Ensayos Antitumor por Modelo de Xenoinjerto
4.
Carbohydr Res ; 344(12): 1474-8, 2009 Aug 17.
Artículo en Inglés | MEDLINE | ID: mdl-19501815

RESUMEN

Glyconanoparticles (GNPs) are water-soluble carbohydrate-functionalized gold nanoclusters with a promising potential to serve as versatile tools in studies ranging from basic chemical glycobiology to clinical applications. In this paper we evaluate the influence of ligand density and presentation on the recognition by protein receptors by examining the interaction of lactose-functionalized GNPs with two different galactose-specific carbohydrate-binding proteins: an enzyme, Escherichia coli beta-galactosidase, and a lectin, Viscum album agglutinin. The results suggest that the proper selection of ligand densities and spacers in GNP functionalization is an important requisite to match the topological requirements of the target receptor while escaping glycosidase degradation.


Asunto(s)
Aglutininas/metabolismo , Oro/química , Nanopartículas del Metal/química , Lectinas de Plantas/metabolismo , beta-Galactosidasa/metabolismo , Secuencia de Carbohidratos , Proteínas de Escherichia coli/metabolismo , Modelos Teóricos , Datos de Secuencia Molecular , Unión Proteica , Viscum album/metabolismo
5.
Carbohydr Res ; 342(3-4): 448-59, 2007 Feb 26.
Artículo en Inglés | MEDLINE | ID: mdl-17173881

RESUMEN

A novel platform for anticancer vaccines has been prepared using glyconanotechnology recently developed in our laboratory. Ten different multifunctional gold glyconanoparticles incorporating sialylTn and Lewis(y) antigens, T-cell helper peptides (TT) and glucose in well defined average proportions and with differing density have been synthesised in one step and characterised using NMR and TEM. Size and nature of the linker were crucial to control kinetics of S-Au bond formation and to achieve the desired ligand ratio on the gold clusters. The technology presented here opens the way for tailoring polyvalent anticancer vaccines candidates and drug delivery carriers with defined average chemical composition.


Asunto(s)
Vacunas contra el Cáncer/síntesis química , Glicoconjugados/química , Nanopartículas del Metal/química , Secuencia de Aminoácidos , Animales , Antígenos de Carbohidratos Asociados a Tumores/química , Secuencia de Carbohidratos , Femenino , Antígenos del Grupo Sanguíneo de Lewis/química , Ratones , Microscopía Electrónica de Transmisión , Datos de Secuencia Molecular , Nanotecnología , Resonancia Magnética Nuclear Biomolecular , Toxoide Tetánico/química
6.
J Am Chem Soc ; 127(17): 6192-7, 2005 May 04.
Artículo en Inglés | MEDLINE | ID: mdl-15853323

RESUMEN

Thermodynamic evidence for the selective Ca(2+)-mediated self-aggregation via carbohydrate-carbohydrate interactions of gold glyconanoparticles functionalized with the disaccharides lactose (lacto-Au) and maltose (malto-Au), or the biologically relevant trisaccharide Lewis X (Le(X)-Au), was obtained by isothermal titration calorimetry. The aggregation process was also directly visualized by atomic force microscopy. It was shown in the case of the trisaccharide Lewis X that the Ca(2+)-mediated aggregation is a slow process that takes place with a decrease in enthalpy of 160 +/- 30 kcal mol(-)(1), while the heat evolved in the case of lactose and maltose glyconanoparticles was very low and thermal equilibrium was quickly achieved. Measurements in the presence of Mg(2+) and Na(+) cations confirm the selectivity for Ca(2+) of Le(X)-Au glyconanoparticles. The relevance of this result to cell-cell adhesion process mediated by carbohydrate-carbohydrate interactions is discussed.


Asunto(s)
Calcio/química , Oro/química , Nanoestructuras/química , Trisacáridos/química , Animales , Calorimetría/métodos , Secuencia de Carbohidratos , Cationes Bivalentes/química , Adhesión Celular/fisiología , Embrión de Pollo , Lactosa/química , Antígeno Lewis X/análogos & derivados , Magnesio/química , Maltosa/química , Microscopía de Fuerza Atómica , Datos de Secuencia Molecular , Neuronas/citología , Oligosacáridos/química , Poríferos/citología , Retina/citología , Termodinámica
7.
Chembiochem ; 5(3): 291-7, 2004 Mar 05.
Artículo en Inglés | MEDLINE | ID: mdl-14997521

RESUMEN

Gold glyconanoparticles (GNPs) have been prepared as new multivalent tools that mimic glycosphingolipids on the cell surface. GNPs are highly soluble under physiological conditions, stable against enzymatic degradation and nontoxic. Thereby GNPs open up a novel promising multivalent platform for biological applications. It has recently been demonstrated that specific tumor-associated carbohydrate antigens (glycosphingolipids and glycoproteins) are involved in the initial step of tumor spreading. A mouse melanoma model was selected to test glyconanoparticles as possible inhibitors of experimental lung metastasis. A carbohydrate-carbohydrate interaction is proposed as the first recognition step for this process. Glyconanoparticles presenting lactose (lacto-GNPs) have been used successfully to significantly reduce the progression of experimental metastasis. This result shows for the first time a clear biological effect of lacto-GNPs, demonstrating the potential application of this glyconanotechnology in biological processes.


Asunto(s)
Oro/uso terapéutico , Lactosa/uso terapéutico , Nanotecnología/métodos , Metástasis de la Neoplasia/tratamiento farmacológico , Animales , Adhesión Celular/efectos de los fármacos , Línea Celular Tumoral , Glicoesfingolípidos , Neoplasias Pulmonares/prevención & control , Neoplasias Pulmonares/secundario , Melanoma Experimental/tratamiento farmacológico , Melanoma Experimental/patología , Ratones , Imitación Molecular , Invasividad Neoplásica/prevención & control , Metástasis de la Neoplasia/prevención & control , Tamaño de la Partícula , Resultado del Tratamiento
8.
Chemistry ; 9(9): 1909-21, 2003 May 09.
Artículo en Inglés | MEDLINE | ID: mdl-12740837

RESUMEN

A simple and versatile methodology is described for tailoring sugar-functionalised gold nanoclusters (glyconanoparticles) that have 3D polyvalent carbohydrate display and globular shapes. This methodology allows the preparation of glyconanoparticles with biologically significant oligosaccharides as well as with differing carbohydrate density. Fluorescent glyconanoparticles have been also prepared for labelling cells in biological tests. The materials are water soluble, stable under physiological conditions and present an exceptional small core size. All of them have been characterised by (1)H NMR, UV and IR spectroscopy, TEM and elemental analysis. Their highly polyvalent network can mimic glycosphingolipid clustering and interactions at the plasma membrane, providing an controlled system for glycobiological studies. Furthermore, they are useful building blocks for the design of nanomaterials.


Asunto(s)
Carbohidratos/química , Glicocálix/química , Oro/química , Microesferas , Secuencia de Carbohidratos , Cromatografía en Capa Delgada , Fluoresceína-5-Isotiocianato , Colorantes Fluorescentes , Indicadores y Reactivos , Ligandos , Imitación Molecular , Datos de Secuencia Molecular , Propiedades de Superficie
11.
Angew Chem Int Ed Engl ; 40(12): 2257-2261, 2001 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-29711834

RESUMEN

Glycosphingolipid clustering and interactions at the cell membrane can be modeled by gold glyconanoparticles prepared with biologically significant oligosaccharides. Such water-soluble gold glyconanoparticles with highly polyvalent carbohydrate displays (see picture, gray hemisphere: gold nanoparticle) have been obtained by a simple and versatile strategy.

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