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1.
Sci Rep ; 14(1): 5946, 2024 03 11.
Article in English | MEDLINE | ID: mdl-38467715

ABSTRACT

The use of dendrimers as drug and nucleic acid delivery systems requires knowledge of their interactions with objects on their way to the target. In the present work, we investigated the interaction of a new class of carbosilane dendrimers functionalized with polyphenolic and caffeic acid residues with human serum albumin, which is the most abundant blood protein. The addition of dendrimers to albumin solution decreased the zeta potential of albumin/dendrimer complexes as compared to free albumin, increased density of the fibrillary form of albumin, shifted fluorescence spectrum towards longer wavelengths, induced quenching of tryptophan fluorescence, and decreased ellipticity of circular dichroism resulting from a reduction in the albumin α-helix for random coil structural form. Isothermal titration calorimetry showed that, on average, one molecule of albumin was bound by 6-10 molecules of dendrimers. The zeta size confirmed the binding of the dendrimers to albumin. The interaction of dendrimers and albumin depended on the number of caffeic acid residues and polyethylene glycol modifications in the dendrimer structure. In conclusion, carbosilane polyphenolic dendrimers interact with human albumin changing its structure and electrical properties. However, the consequences of such interaction for the efficacy and side effects of these dendrimers as drug/nucleic acid delivery system requires further research.


Subject(s)
Caffeic Acids , Dendrimers , Nucleic Acids , Humans , Serum Albumin, Human/metabolism , Dendrimers/chemistry , Silanes/chemistry
3.
Pharmaceutics ; 12(8)2020 Jul 24.
Article in English | MEDLINE | ID: mdl-32722069

ABSTRACT

A new family of polyphenolic carbosilane dendrimers functionalized with ferulic, caffeic, and gallic acids has been obtained through a straightforward amidation reaction. Their antioxidant activity has been studied by different techniques such as DPPH (2,2'-diphenyl-1-picrylhydrazyl) radical scavenging assay, FRAP assay (ferric reducing antioxidant power), and cyclic voltammetry. The antioxidant analysis showed that polyphenolic dendrimers exhibited higher activities than free polyphenols in all cases. The first-generation dendrimer decorated with gallic acid stood out as the best antioxidant compound, displaying a correlation between the number of hydroxyl groups in the polyphenol structure and the antioxidant activity of the compounds. Moreover, the antibacterial capacity of these new systems has been screened against Gram-positive (+) and Gram-negative (-) bacteria, and we observed that polyphenolic dendrimers functionalized with caffeic and gallic acids were capable of decreasing bacterial growth. In contrast, ferulic carbosilane dendrimers and free polyphenols showed no effect, establishing a correlation between antioxidant activity and antibacterial capacity. Finally, a viability assay in human skin fibroblasts cells (HFF-1) allowed for corroborating the nontoxicity of the polyphenolic dendrimers at their active antibacterial concentration.

4.
Int J Mol Sci ; 21(13)2020 Jun 30.
Article in English | MEDLINE | ID: mdl-32629868

ABSTRACT

Gene therapy is a promising approach in cancer treatment; however, current methods have a number of limitations mainly due to the difficulty in delivering therapeutic nucleic acids to their sites of action. The application of non-viral carriers based on nanomaterials aims at protecting genetic material from degradation and enabling its effective intracellular transport. We proposed the use of silver nanoparticles (AgNPs) surface-modified with carbosilane dendrons as carriers of anticancer siRNA (siBcl-xl). Using gel electrophoresis, zeta potential and hydrodynamic diameter measurements, as well as transmission electron microscopy, we characterized AgNP:siRNA complexes and demonstrated the stability of nucleic acid in complexes in the presence of RNase. Hemolytic properties of free silver nanoparticles and complexes, their effect on lymphocyte proliferation and cytotoxic activity on HeLa cells were also examined. Confocal microscopy proved the effective cellular uptake of complexes, indicating the possible use of this type of silver nanoparticles as carriers of genetic material in gene therapy.


Subject(s)
Drug Delivery Systems/methods , Metal Nanoparticles/administration & dosage , Silanes/chemistry , Dendrimers/administration & dosage , Dendrimers/chemistry , Genetic Therapy/methods , HeLa Cells , Hemolysis , Humans , Metal Nanoparticles/chemistry , Microscopy, Electron, Transmission , Nucleic Acids/therapeutic use , RNA, Small Interfering/genetics , RNA, Small Interfering/pharmacology , Silver/chemistry
5.
RSC Adv ; 10(34): 20083-20088, 2020 May 26.
Article in English | MEDLINE | ID: mdl-35520432

ABSTRACT

The anionic carbosilane (CBS) dendrimer with sulfonate groups G2-S16 is a promising compound for the preparation of a microbicide gel to prevent HIV infection. However, until now its synthesis required aggressive conditions. Hence, a reliable synthetic procedure is very important to face GMP conditions and clinical trials. In this study, G2-S16 has been prepared by a new approach that involves the addition of an amine-terminated dendrimer to ethenesulfonyl fluoride (C2H3SO3F, ESF) and then transformation to the sulfonate dendrimer by treatment with a base. This strategy also makes feasible the synthesis of a labelled sulfonate dendrimer (G2-S16-FITC) to be used as a molecular probe for in vivo experiments. Interestingly, G2-S16-FITC enters into human peripheral blood mononuclear cells (PBMCs).

6.
Mikrochim Acta ; 186(8): 508, 2019 07 04.
Article in English | MEDLINE | ID: mdl-31273524

ABSTRACT

The feasibility of using carbosilane dendronized gold nanoparticles (GNPs) for protein sample preparation was evaluated. Three different dendrons with three different generations (1G, 2G, and 3G) were employed to modify the GNPs, viz. sulfonate terminated (STC-GNPs), carboxylate terminated (CTC-GNPs), and trimethylammonium terminated (ATC-GNPs) dendrons. The synthesis of the CTC-GNP is described. The other dendronized GNPs were synthesized using previously described routes. Bovine serum albumin, lysozyme, and myoglobin were employed to study the potential of GNPs to interact with proteins. The interaction between the GNPs and the proteins was evaluated using fluorescence spectroscopy and polyacrylamide gel electrophoresis. The CTC-GNPs and STC-GNPs under acidic and neutral conditions, respectively, promoted the establishment of electrostatic interactions with positively charged proteins. Proteins from 10 to 75 kDa molecular weights interacted with GNPs at protein: nanoparticle ratios of 1:0.25. The GNPs were applied to the extraction of proteins from a peach seed. In the authors' perception, the method is a clean alternative to established extraction methods based on the use of organic or polluting chemicals. Graphical abstract Schematic representation of the interaction of peach seeds proteins and carbosilane dendron coated gold nanoparticles, and the electrophoretic profiles of extracted proteins.


Subject(s)
Anthracenes/chemistry , Gold/chemistry , Metal Nanoparticles/chemistry , Proteins/chemistry , Silanes/chemistry , Hydrogen-Ion Concentration , Muramidase/chemistry , Myoglobin/chemistry , Proteins/metabolism , Serum Albumin, Bovine/chemistry , Spectrometry, Fluorescence , Static Electricity
7.
Int J Biol Macromol ; 118(Pt B): 1773-1780, 2018 Oct 15.
Article in English | MEDLINE | ID: mdl-29997045

ABSTRACT

Functionalization of gold nanoparticles by different chemical groups is an important issue regarding the biomedical applications of such particles. Therefore we have analyzed the interaction between gold nanoparticles functionalized by carbosilane dendrons with human serum albumin at different pHs, and in the presence of the protein unfolding agent, guanidine hydrochloride, using circular dichroism, zeta-potential and fluorescence quenching. The effect of a nanoparticle dendronization and pure dendrons on the immunoreactivity of albumin was estimated using ELISA. In addition, the tool to estimate the binding capacity of dendronized gold nanoparticles using a hydrophobic fluorescent probe 1,8-ANS (1-anilinonaphthalene-8-sulfonic acid) was chosen. We concluded that the effect of a nanoparticle on the structure, immunochemical properties and unfolding of albumin significantly decreased with second and third generations dendrons attached. Differences in pH dependence of the interaction between nanoparticles, their dendrons and albumin showed several effects of the "dendritic corona" and the metallic part of nanoparticle on the protein. These interactions indicate changes in the immunoreactivity of the protein, whereas dendron coating per se had no effect. Thus, dendronization of gold nanoparticles helps to shield them from interactions with plasma proteins.


Subject(s)
Cations , Dendrimers , Gold , Metal Nanoparticles , Serum Albumin, Human/chemistry , Silanes , Cations/chemistry , Circular Dichroism , Dendrimers/chemistry , Gold/chemistry , Humans , Hydrogen-Ion Concentration , Kinetics , Metal Nanoparticles/chemistry , Protein Binding , Serum Albumin, Human/metabolism , Silanes/chemistry , Structure-Activity Relationship
8.
Int J Biol Macromol ; 108: 936-941, 2018 Mar.
Article in English | MEDLINE | ID: mdl-29104054

ABSTRACT

Gold nanoparticles are new kinds of nanomaterials. Their large surface-to-volume ratio, stability, excellent biocompatibility, low toxicity and functionality make them very attractive for biomedical applications. Therefore we have analyzed how dendronized gold nanoparticles interact with human alpha-1-microglobulin. This is a glycoprotein of ∼30kDa present in blood plasma and some tissues of the human body. Comparing 3 nanoparticles with different dendronization, we conclude that the effect of a nanoparticle on the structure of alpha-1-microglobulin significantly decreased with second and third generations dendrons as a result of less exposure of the metal cores in the nanoparticles. These interactions indicate weak changes in the immunochemical properties of the protein, whereas the dendron coating had no effect. Thus, dendronization of gold nanoparticles helps to modify their binding properties by shielding them from interactions with plasma proteins.


Subject(s)
Alpha-Globulins/chemistry , Dendrimers/chemistry , Gold/chemistry , Metal Nanoparticles/chemistry , Humans , Models, Molecular , Particle Size , Protein Conformation
9.
Int J Pharm ; 528(1-2): 55-61, 2017 Aug 07.
Article in English | MEDLINE | ID: mdl-28577968

ABSTRACT

Water soluble silver nanoparticles (AgNPs) capped with cationic carbosilane dendrons have been synthesized by direct reaction in water of dendrons, silver precursor and a reducing agent. These nanoparticles have been characterized by nuclear magnetic resonance (NMR), transmission electron microscopy (TEM), dynamic light scattering (DLS), thermogravimetric analysis (TGA), ultraviolet spectroscopy (UV), elemental analysis, and zeta potential (ZP). The antibacterial and antifungal properties of the cationic dendrons and dendronized AgNPs and AuNPs with these dendrons have been evaluated against Gram-negative and Gram-positive bacterial -including resistant strains- and yeast strains, respectively. The results stand out for the activity of AgNPs covered with first generation dendron compared with this free dendron and corresponding dendronized AuNPs.


Subject(s)
Anti-Bacterial Agents/pharmacology , Antifungal Agents/pharmacology , Dendrimers/chemistry , Metal Nanoparticles/chemistry , Silanes/chemistry , Gold , Silver
10.
Dalton Trans ; 46(27): 8736-8745, 2017 Jul 11.
Article in English | MEDLINE | ID: mdl-28091639

ABSTRACT

Gold nanoparticles (AuNPs) and polycationic macromolecules are used as gene carriers. Their behaviour is dependent on several factors, such as the size and type of the framework, charge, etc. We have combined both types of systems and prepared AuNPs covered with cationic carbosilane dendrons with the aim to evaluate their biocompatibility. Water soluble dendronized cationic AuNPs were prepared following a straightforward procedure from dendrons, a gold precursor and a reducing agent in water and were characterized by 1H NMR, transmission electron microscopy (TEM), dynamic light scattering (DLS), thermogravimetric analysis (TGA), ultraviolet spectroscopy (UV), and zeta potential (ZP). The biological properties of dendrons and AuNPs were determined by hemolysis, platelet aggregation and lymphocyte proliferation. These assays reflect modification of dendron properties when covering nanoparticles. For dendrons, hemolysis and platelet aggregation are generation dependent whilst, for AuNPs these properties are related to the bigger size of NPs. On the other hand, none of the systems induced lymphocyte proliferation. Selected cationic dendrons and AuNPs were chosen for gene delivery experiments employing a small interference RNA (siRNA Nef) against human immunodeficiency virus (HIV).


Subject(s)
Dendrimers/chemistry , Drug Carriers/chemical synthesis , Drug Carriers/pharmacology , Gold/chemistry , Gold/pharmacology , Metal Nanoparticles/chemistry , Silanes/chemistry , Cell Proliferation/drug effects , Chemistry Techniques, Synthetic , Drug Carriers/chemistry , HIV/genetics , Hemolysis/drug effects , Humans , Lymphocytes/cytology , Lymphocytes/drug effects , Platelet Aggregation/drug effects , RNA, Small Interfering/chemistry , RNA, Small Interfering/genetics
11.
Chemistry ; 22(9): 2987-99, 2016 Feb 24.
Article in English | MEDLINE | ID: mdl-26875938

ABSTRACT

Anionic carbosilane dendrons decorated with sulfonate functions and one thiol moiety at the focal point have been used to synthesize water-soluble gold nanoparticles (AuNPs) through the direct reaction of dendrons, gold precursor, and reducing agent in water, and also through a place-exchange reaction. These nanoparticles have been characterized by NMR spectroscopy, TEM, thermogravimetric analysis, X-ray photoelectron spectroscopy (XPS), UV/Vis spectroscopy, elemental analysis, and zeta-potential measurements. The interacting ability of the anionic sulfonate functions was investigated by EPR spectroscopy with copper(II) as a probe. Different structures and conformations of the AuNPs modulate the availability of sulfonate and thiol groups for complexation by copper(II). Toxicity assays of AuNPs showed that those produced through direct reaction were less toxic than those obtained by ligand exchange. Inhibition of HIV-1 infection was higher in the case of dendronized AuNPs than in dendrons.


Subject(s)
Anions/chemistry , Antiviral Agents/chemical synthesis , Antiviral Agents/pharmacology , Dendrimers/chemistry , Gold/chemistry , HIV-1/chemistry , Metal Nanoparticles/chemistry , Silanes/chemistry , Antiviral Agents/chemistry , Electron Spin Resonance Spectroscopy , Photoelectron Spectroscopy , Spectrophotometry, Ultraviolet
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