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1.
Bioconjug Chem ; 29(10): 3352-3361, 2018 10 17.
Artigo em Inglês | MEDLINE | ID: mdl-30215508

RESUMO

Galectins (Gal) are a family of glycan-binding proteins characterized by their affinity for ß-galactosides. Galectin-1 (Gal-1), a dimeric lectin with two galactoside-binding sites, regulates cancer progression and immune responses. Coordination chemistry has been engaged to develop versatile multivalent neoglycoconjugates for binding Gal-1. In this study we report a fast and original method to synthesize hybrid gold nanoparticles in which a hydrochloride lactose-modified chitosan, named CTL, is mixed with dicarboxylic acid-terminated polyethylene glycol (PEG), leading to shell-like hybrid polymer-sugar-metal nanoparticles (CTL-PEG-AuNPs). The aim of this paper is to preliminarily study the interaction of the CTL-PEG-AuNPs with a target protein, namely, Gal-1, under specific conditions. The molecular interaction has been measured by Transmission Electron Microscopy (TEM), UV-vis, and Raman Spectroscopy on a large range of Gal-1 concentrations (from 0 to 10-12 M). We observed that the interaction was strongly dependent on the Gal-1 concentration at the surface of the gold nanoparticles.


Assuntos
Quitosana/química , Galectina 1/química , Ouro/química , Lactose/química , Polietilenoglicóis/química , Humanos , Nanopartículas Metálicas/química , Microscopia Eletrônica de Transmissão , Espectrofotometria Ultravioleta , Análise Espectral Raman
3.
Mar Drugs ; 14(10)2016 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-27763505

RESUMO

Herein we investigate the structure/function relationships of fucoidans from Ascophyllum nodosum to analyze their pro-angiogenic effect and cellular uptake in native and glycosaminoglycan-free (GAG-free) human endothelial cells (HUVECs). Fucoidans are marine sulfated polysaccharides, which act as glycosaminoglycans mimetics. We hypothesized that the size and sulfation rate of fucoidans influence their ability to induce pro-angiogenic processes independently of GAGs. We collected two fractions of fucoidans, Low and Medium Molecular Weight Fucoidan (LMWF and MMWF, respectively) by size exclusion chromatography and characterized their composition (sulfate, fucose and uronic acid) by colorimetric measurement and Raman and FT-IR spectroscopy. The high affinities of fractionated fucoidans to heparin binding proteins were confirmed by Surface Plasmon Resonance. We evidenced that LMWF has a higher pro-angiogenic (2D-angiogenesis on Matrigel) and pro-migratory (Boyden chamber) potential on HUVECs, compared to MMWF. Interestingly, in a GAG-free HUVECs model, LMWF kept a pro-angiogenic potential. Finally, to evaluate the association of LMWF-induced biological effects and its cellular uptake, we analyzed by confocal microscopy the GAGs involvement in the internalization of a fluorescent LMWF. The fluorescent LMWF was mainly internalized through HUVEC clathrin-dependent endocytosis in which GAGs were partially involved. In conclusion, a better characterization of the relationships between the fucoidan structure and its pro-angiogenic potential in GAG-free endothelial cells was required to identify an adapted fucoidan to enhance vascular repair in ischemia.


Assuntos
Indutores da Angiogênese/metabolismo , Indutores da Angiogênese/farmacologia , Ascophyllum/química , Polissacarídeos/metabolismo , Polissacarídeos/farmacologia , Indutores da Angiogênese/química , Caveolina 1/química , Movimento Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Cromatografia em Gel , Clatrina/química , Endocitose/efeitos dos fármacos , Glicosaminoglicanos/metabolismo , Células Endoteliais da Veia Umbilical Humana , Humanos , Peso Molecular , Neovascularização Fisiológica/efeitos dos fármacos , Polissacarídeos/química , Relação Estrutura-Atividade
4.
Nanotechnology ; 26(5): 055101, 2015 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-25573907

RESUMO

In this paper, we propose a multi-parametric in vitro study of the cytotoxicity of gold nanoparticles (GNPs) on human endothelial cell (HUVEC). The cytotoxicity is evaluated by incubating cells with six different GNP types which have two different morphologies: spherical and flower-shaped, two sizes (∼15 and ∼50 nm diameter) and two surface chemistries (as prepared form and PEGylated form). Our results showed that by increasing the concentration of GNPs the cell viability decreases with a toxic concentration threshold of 10 pM for spherical GNPs and of 1 pM for flower-shaped GNPs. Dark field images, flow cytometry and spreading test revealed that flower-shaped GNPs have more deleterious effects on the cell mechanisms than spherical GNPs. We demonstrated that the main parameter in the evaluation of the GNPs toxicity is the GNPs roughness and that this effect is independent on the surface chemistry. We assume that this behavior is highly related to the efficiency of the GNPs internalization within the cells and that this effect is enhanced due to the specific geometry of the flower-shaped GNPs.


Assuntos
Células Endoteliais/efeitos dos fármacos , Ouro/toxicidade , Nanopartículas Metálicas/toxicidade , Células Cultivadas , Humanos , Nanopartículas Metálicas/ultraestrutura , Tamanho da Partícula , Propriedades de Superfície
6.
Int J Nanomedicine ; 17: 4105-4118, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36111314

RESUMO

Introduction: The realization of MRI contrast agents through chemical protocols of functionalization is a strong domain of research. In this work, we developed and formulated a novel hybrid gold nanoparticle system in which a gold salt (HAuCl4) is combined with dotarem, an MRI contrast agent (DOTA) by chelation (Method IN) and stabilized by a lactose-modified chitosan polymer (CTL; Chitlac) to form DOTA IN-CTL AuNPs. Result and Discussion: The authors demonstrate the biological efficiency of these nanoparticles in the case of three cell lines: Mia PaCa-2 (human pancreatic cancer cell line), TIB-75 (murine liver cell line) and KKU-M213 (cholangiocarcinoma cell line). DOTA IN-CTL AuNPs are stable under physiological conditions, are nontoxic, and are very efficient as PTT agents. The highlights, such as high stability and preliminary MRI in vitro and in vivo models, may be suitable for diagnosis and therapy. Conclusion: We proved that DOTA IN-CTL AuNPs have several advantages: i) Biological efficacy on three cell lines: MIA PaCa-2 (human pancreatic cancer cell line), TIB-75 (murine liver cell line) and KKU-M213 (cholangiocarcinoma cell line); ii) high stability, and no-toxicity; iii) high efficiency as a PPT agent. The study conducted on MRI in vitro and in vivo models will be suitable for diagnosis and therapy.


Assuntos
Quitosana , Colangiocarcinoma , Nanopartículas Metálicas , Neoplasias Pancreáticas , Animais , Quitosana/química , Meios de Contraste/química , Ouro/química , Compostos Heterocíclicos com 1 Anel , Humanos , Lactose , Meglumina , Nanopartículas Metálicas/química , Camundongos , Compostos Organometálicos , Neoplasias Pancreáticas/diagnóstico por imagem , Polímeros/química , Neoplasias Pancreáticas
8.
Nanoscale Adv ; 3(21): 6144-6156, 2021 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-36133939

RESUMO

Flavoproteins play an important role in the regulatory process of cell life, and they are involved in several redox reactions that regulate the metabolism of carbohydrates, amino acids, and lipids. The development of effective drug delivery systems is one of the major challenges in the fight against cancer. This study involves a nanomedicine pathway to encapsulate the cofactor flavin adenine dinucleotide (FAD) using polymeric gold nanoparticles (PEG-AuNPs) through two chemical methods of functionalization (chelation (IN); carbodiimide chemistry (ON)). These hybrid gold nanoparticles and their precursors were characterized by analytical techniques (Raman, UV-Vis, and H1-NMR spectroscopy and transmission electron microscopy (TEM)) which confirmed the grafting of the cofactor agent. The results of the computational studies (Density Functional Theory (DFT)) were in agreement with the experimental observations. We also monitored the interaction of our hybrid nanoparticle systems with small aptamers (APT) in order to validate the hypotheses on the biomolecular mechanisms and also investigate their biological efficiency on pancreatic cancer cells (MIAPaCa-2 cells).

9.
Int J Nanomedicine ; 16: 2219-2236, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33762822

RESUMO

INTRODUCTION: In this paper, we have designed and formulated, a novel synthesis of doxorubicin (DOX) loaded bimetallic gold nanorods in which gold salt (HAuCl4) is chelated with anthracycline (DOX), diacid polyethylene-glycol (PEG-COOH) and gadolinium salt (GdCl3 * 6 H2O) to form DOX IN-Gd-AuNRs compared with DOX ON-Gd-AuNRs in which the drug was grafted onto the bimetallic pegylated nanoparticle surface by electrostatic adsorption. MATERIAL AND METHOD: The physical and chemical evaluation was performed by spectroscopic analytical techniques (Raman spectroscopy, UV-Visible and transmission electron microscopy (TEM)). Magnetic features at 7T were also measured. Photothermal abilities were assessed. Cytotoxicity studies on MIA PaCa-2, human pancreatic carcinoma and TIB-75 hepatocytes cell lines were carried out to evaluate their biocompatibility and showed a 320 fold higher efficiency for DOX after encapsulation. RESULTS: Exhaustive physicochemical characterization studies were conducted showing a mid size of 20 to 40 nm diameters obtained with low polydispersity, efficient synthesis using seed mediated synthesis with chelation reaction with high scale-up, long duration stability, specific doxorubicin release with acidic pH, strong photothermal abilities at 808 nm in the NIR transparency window, strong magnetic r1 relaxivities for positive MRI, well adapted for image guided therapy and therapeutical purpose in biological tissues. CONCLUSION: In this paper, we have developed a novel theranostic nanoparticle composed of gadolinium complexes to gold ions, with a PEG biopolymer matrix conjugated with antitumoral doxorubicin, providing multifunctional therapeutic features. Particularly, these nano conjugates enhanced the cytotoxicity toward tumoral MIAPaCa-2 cells by a factor of 320 compared to doxorubicin alone. Moreover, MRI T1 features at 7T enables interesting positive contrast for bioimaging and their adapted size for potential passive targeting to tumors by Enhanced Permeability Retention. Given these encouraging antitumoral and imaging properties, this bimetallic theranostic nanomaterial system represents a veritable promise as a therapeutic entity in the field of medicinal applications.


Assuntos
Doxorrubicina/uso terapêutico , Gadolínio/química , Ouro/química , Nanotubos/química , Nanomedicina Teranóstica , Animais , Antibióticos Antineoplásicos/farmacologia , Antibióticos Antineoplásicos/uso terapêutico , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Doxorrubicina/farmacologia , Liberação Controlada de Fármacos , Endocitose , Humanos , Concentração Inibidora 50 , Imageamento por Ressonância Magnética , Camundongos , Nanotubos/ultraestrutura , Neoplasias/tratamento farmacológico , Terapia Fototérmica , Espectrofotometria Ultravioleta
10.
Nanoscale ; 13(29): 12443-12453, 2021 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-34251385

RESUMO

We study the interaction between one aptamer and its analyte (the MnSOD protein) by the combination of surface-enhanced Raman scattering and multivariate statistical analysis. We observe the aptamer structure and its evolution during the interaction under different experimental conditions (in air or in buffer). Through the spectral treatment by principal component analysis of a large set of SERS data, we were able to probe the aptamer conformations and orientations relative to the surface assuming that the in-plane nucleoside modes are selectively enhanced. We demonstrate that the aptamer orientation and thus its flexibility rely strongly on the presence of a spacer of 15 thymines and on the experimental conditions with the aptamer lying on the surface in air and standing in the buffer. We reveal for the first time that the interaction with MnSOD induces a large loss of flexibility and freezes the aptamer structure in a single conformation.


Assuntos
Aptâmeros de Nucleotídeos , Técnicas Biossensoriais , Análise Espectral Raman
11.
Opt Express ; 18(8): 7753-62, 2010 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-20588616

RESUMO

A simple and fast time-domain method for localizing inclusions, fluorescent optical probes or absorbers, is presented. The method offers new possibilities for situations where complete tomographic measurements are not permitted by the examined object, for example in endoscopic examination of the human prostate or the oesophagus. Feasibility has been envisioned with a phantom study conducted on a point-like fluorochrome embedded in a diffusing medium mimicking the optical properties of biological tissues.


Assuntos
Nefelometria e Turbidimetria/instrumentação , Nefelometria e Turbidimetria/métodos , Fenômenos Ópticos , Corantes Fluorescentes/química , Propriedades de Superfície , Fatores de Tempo
12.
Colloids Surf B Biointerfaces ; 185: 110588, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31654887

RESUMO

Galectins (Gal) are a family of dimeric lectins, composed by two galactoside-binding sites implicated in the regulation of cancer progression and immune responses. In this study, we report for the first time the synthesis and the physical-chemical characterization of galectin-1-complex-gold COOH-terminated polyethlenglicole (PEG)-coated NPs (Gal-1 IN PEG-AuNPs) and their ability to recognize glucose in an aqueous solution with a concentration varying from 10 mM to 100 pM. The chemical protocol consistsof three steps: (i) complexation between galectin-1Gal-1 and tetrachloroauric acid (HAuCl4) to form gold-protein grains; (ii) staking process of COOH-terminated polyethlenglicole molecules (PEG) onto Gal-1-Au complex and (iii) reduction of hybrid metal ions to obtain a colloidal stable solution. During the complexation, the spectral signatures related to the Gal-1 orientation on the gold surface have been found to change due to its protonation state. The effective glucose monitoring was detected by UV-vis, Raman spectroscopy and Transmission Electron Microscopy (TEM). Overall, we observed that the interaction is strongly dependent on the Gal-1 conformation at the surface of gold nanoparticles.


Assuntos
Colorimetria/métodos , Galectina 1/química , Galectina 1/metabolismo , Glucose/análise , Ouro/química , Nanopartículas Metálicas/química , Polietilenoglicóis/química , Glucose/metabolismo , Humanos
13.
ACS Omega ; 5(23): 13851-13859, 2020 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-32566851

RESUMO

Aptamers are small biomolecules composed of 20-100 nucleotides that recognize target molecules in three-dimensional structures. These natural targeting molecules have attracted interest in the biomedical field as biomarkers for cancer diagnostics. In this study, we investigated the interaction of a characteristic aptamer with its target protein, Cu, Zn superoxide dismutase (SOD 4), on a gold nanoparticle (AuNP) surface under experimental conditions. For this purpose, we applied two protocols to coat SOD 4 aptamer (APT) on the nanoparticle surface: carbodiimide chemistry (EDC/NHS) (Method ON) and a complexation methodology (Method IN). The nano-aptamer's interactions with SOD 4 were detected by UV-vis absorption and Raman spectroscopy in a range of protein concentrations (from 1 µM to 50 nM). We believe that the interaction is heavily dependent on the nature of the biomarker (SOD 4) and also on the steric arrangement of the aptamer on the gold nanoparticle surface. The lowest detectable concentration (limit of detection, LOD) was about 2 nM for APT IN PEG-AuNPs and 8 nM for APT ON PEG-AuNPs. For the first time, we demonstrated a very sensitive detection of SOD 4 in the nanomolar concentration range with new ways of biosensor synthesis (APT IN and ON), providing a very strong tool to understand the effect of aptamer conformation to detect SOD 4.

14.
J Med Chem ; 63(13): 7410-7421, 2020 07 09.
Artigo em Inglês | MEDLINE | ID: mdl-32524814

RESUMO

This paper emphasizes the synthesis of novel hybrid drug nanoparticles (Hyb-D-AuNPs) based on gold-temozolomide (TMZ) complexes combined with gemcitabine (GEM) and decitabine (DAC) to improve the efficiency and reduce the resistance of U87 malignant glial cells against TMZ. All products were evaluated by several spectroscopic techniques (Raman, UV-Vis) and transmission electron microscopy (TEM). Besides, for therapeutic purposes, the effect of these nanoparticles on cell proliferation and toxicity was evaluated, which clearly showed a synergic action of TMZ and GEM. Through the analysis of the exometabolome by nuclear magnetic resonance (NMR), the metabolic changes in the culture medium were measured in glial cells. Moreover, these nanoparticles are especially appropriated to the thermal destruction of cancer in the case of photothermal therapy due to their photothermal heating properties. This study presents an original chemical approach that it could play a central role in the field of nanomedicine, with novel perspectives for the development of new drugs and active targeting in glioblastoma multiforme (GBM) cancer therapy.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Decitabina/farmacologia , Desoxicitidina/análogos & derivados , Glioblastoma/tratamento farmacológico , Nanoconjugados/administração & dosagem , Temozolomida/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Decitabina/administração & dosagem , Desoxicitidina/administração & dosagem , Desoxicitidina/farmacologia , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Resistencia a Medicamentos Antineoplásicos , Sinergismo Farmacológico , Glioblastoma/metabolismo , Glioblastoma/patologia , Ouro/química , Humanos , Espectroscopia de Ressonância Magnética , Nanopartículas Metálicas/química , Nanoconjugados/química , Estudo de Prova de Conceito , Espectrofotometria Ultravioleta , Temozolomida/administração & dosagem , Gencitabina
15.
Nanoscale Adv ; 2(11): 5231-5241, 2020 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-36132041

RESUMO

In this work, we bring back a rapid way to conceive doxorubicin (DOX) hybrid gold nanoparticles, in which DOX and Au(iii) ions were complexed with a hydrochloride-lactose-modified chitosan, named CTL and dicarboxylic acid-terminated polyethylene-glycol (PEG), leading to hybrid polymer-sugar-metal nanoparticles (DOX-AuGSs). All formulations were assessed by spectroscopic techniques (Raman and UV-Vis) and transmission electron microscopy (TEM). To estimate the therapeutic effect of DOX-AuGSs in liver cancer, murine HepG2 cells were used to induce a hepatic carcinoma model in nude mice. The survival time of the tumor-bearing mice, body weight and tumor volume were measured and recorded. The cytokines were used to detect the serum inflammatory factors, and the blood cell analyzer was used to determine the blood cell content of different groups of nude mice. The outcomes demonstrate that DOX-AuGCs significantly suppressed the tumor growth derived from human HepG2 injection and reduce the tumor index without affecting the body weight of mice. Moreover, DOX-AuGCs significantly reduced the serum levels of cytokines IL-6, TNF-α and IL-12 P70. Finally, a histological analysis of the heart tissue sections indicated that DOX-AuGCs significantly reduce the chronic myocardial toxicity of DOX during the period of treatment.

16.
Nanoscale ; 11(8): 3665-3673, 2019 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-30741295

RESUMO

The study of protein interactions with gold nanoparticles (GNP) is a key step prior to any biomedical application. These interactions depend on many GNP parameters such as size, surface charge, chemistry, and shape. In this work, we propose to use a sensitive technique named scattering correlation spectroscopy or SCS to study protein interactions with GNP. SCS allowed the investigation of the GNP hydrodynamic radius with a very high sensitivity before and after interaction with proteins. No labeling is needed. As a proof-of-concept, two of the most used morphologies of GNP-based nanovectors have been used within this work: spherical-shaped GNP (GNS) and branched-shaped GNP (GNU). The measurement of several parameters such as the number of proteins binding to one GNP, the binding affinity and the cooperativeness of binding for three different plasma proteins on the GNP surface was carried out. While GNS showed an increase in the hydrodynamic radius, indicating that each kind of protein binds on the GNS in a specific orientation, GNU showed different orientations of proteins due to their multi-oriented surfaces (tips) with a higher surface to volume area. Quantitative data based on the Hill model were extracted to obtain the affinity of the proteins to both GNS and GNU surfaces. Data variations can be understood in terms of the electrostatic properties of the proteins, which interact differently with the negatively charged GNP surfaces.

17.
J Colloid Interface Sci ; 513: 205-213, 2018 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-29153714

RESUMO

The use of phosphonate ligands to modify the nanoparticle (NPs) surface has attracted a strong interest in the last years for the design of highly functional hybrid materials. Here, we applied a methodology to synthesize bisphosphonates having functionalized PEG side chains with a specific length in order to design a novel class of hybrid nanomaterials composed by tetraphosphonate-complex-gold COOH-terminated PEG-coated NPs (Bis-PO-PEG-AuNPs). The synthetic approach consist in three steps: (1) Complexation between new phosphonate ligands (Bis PO) and tetrachloroauric acid (HAuCl4) to form gold clusters; (2) adsorption of COOH-terminated PEG molecules (PEG) onto Bis PO-Au complex; (3) reduction of metal ions in that vicinity, growth of gold particles and colloidal stabilization. The obtained snow-shape-like hybrid nanoparticles, have been characterized by ultra-violet/visible, Raman spectroscopies, and electron microscopy imaging, involving their optical properties and photothermal activity in pancreatic adenocarcinoma cancer cells (PDAC).


Assuntos
Carcinoma Ductal Pancreático/terapia , Nanopartículas Metálicas/administração & dosagem , Compostos Organofosforados/administração & dosagem , Neoplasias Pancreáticas/terapia , Fototerapia , Polietilenoglicóis/química , Ouro/química , Humanos , Ligantes , Nanopartículas Metálicas/química , Compostos Organofosforados/química , Células Tumorais Cultivadas
20.
Med Sci (Paris) ; 22(10): 853-8, 2006 Oct.
Artigo em Francês | MEDLINE | ID: mdl-17026939

RESUMO

A new technique in microscopy is now available which permits to image specific molecular bonds of chemical species present in cells and tissues. The so called Coherent Anti-Stokes Raman Scattering (CARS) approach aims at maximizing the light matter interaction between two laser pulses and an intrinsic molecular vibrational level. This is possible through a non linear process which gives rise to a coherent radiation that is greatly enhanced when the frequency difference between the two laser pulses equals the Raman frequency of the aimed molecular bond. Similar to confocal microscopy, the technique permits to build an image of a molecular density within the sample but doesn't require any labelling or staining since the contrast uses the intrinsic vibrational levels present in the sample. Images of lipids in membranes and tissues have been reported together with their spectral analysis. In the case of very congested media, it is also possible to use a non invasive labelling such as deuterium which shifts the molecular vibration of the C-H bond down to the C-D bond range which falls in a silent region of the cell and tissue vibrational spectra. Such an approach has been used to study lipid phase in artificial membranes. Although the technique is still under development, CARS has now reach a maturity which will permit to bring the technology at a commercial stage in the near future. The last remaining bottleneck is the laser system which needs to be simplified but solutions are now under evaluation. When combined with others more conventional techniques, CARS should give its full potential in imaging unstained samples and like two photons techniques has the potential of performing deep tissues imaging.


Assuntos
Microscopia , Desenho de Equipamento , Técnicas Histológicas , Microscopia/instrumentação , Análise Espectral Raman
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