7 research outputs found
Synthesis of degradable cationic carbosilane dendrimers based on Si-O or ester bonds
Several cationic carbosilane dendrimers have been synthesized containing two different types of degradable
bonds: SieO and ester bonds. The first type of systems was prepared by reacting carbosilane
dendrimers containing peripheral SieCl bonds with first generation dendrons presenting a eOH function
at the focal point and amine peripheral functions. The second type of systems was prepared by esterification
between a dendrimer containing acid groups and an alcoholamine. The stability in water of both
types of cationic systems was evaluatedMinisterio de EconomĂa y Empres
PEGylated AgNP covered with cationic carbosilane dendrons to enhance antibacterial and inhibition of biofilm properties
This work focuses on preparation of silver nanoparticles (AgNP) covered with cationic carbosilane dendrons and poly(ethylene glycol) (PEG). It is well known that AgNP and cationic carbosilane dendritic systems present antibacterial properties. On the other hand, PEG ligand provides antifouling properties and improved biocompatibility. Hence, combination of both ligands, carbosilane dendrons and PEG, on the AgNP surface can be a way to improve antibacterial capacity of AgNP. The new family of heterofunctionalized AgNP has been directly synthesized using silver precursor and cationic carbosilane dendrons and PEG ligands containing a thiol moiety. AgNP were characterized by TEM, TGA, UV, H-1 NMR, DLS, Z potential, XRD. The antibacterial capacity of these systems was evaluated against E. coli and S. aureus. The results confirmed the influence of both silver core and cationic carbosilane dendrons on the activity of these systems. The behaviour obtained for PEGylated systems were slightly lower than for non-PEGylated AgNP. However, hemolysis assays demonstrated that this decrease was compensated for by the greater biocompatibility. To more completely characterize the improvements of PEGylation on dendronized AgNP, one non-PEGylated and one PEGylated AgNP were tested for resistance in a planktonic state. Both AgNPs barely affected the minimum inhibitory concentration (MIC) whereas reference antibiotics generated significant resistance. In addition, relevant improvement in biofilm inhibition was achieved by dendronized AgNP after PEGylation.Universidad de AlcaláMinisterio de EconomĂa, Industria y CompetitividadJunta de Comunidades de Castilla-La ManchaComunidad de Madri
Bacteria capture with magnetic nanoparticles modified with cationic carbosilane dendritic systems
Bacteria elimination from water sources is key to obtain drinkable water. Hence, the design of systems with ability to interact with bacteria and remove them from water is an attractive proposal. A diversity of polycationic macromolecules has shown bactericide properties, due to interactions with bacteria membranes. In this work, we have grafted cationic carbosilane (CBS) dendrons and dendrimers on the surface of iron oxide magnetic nanoparticles (MNP), leading to NP (ca. 10 nm) that interact with bacteria by covering bacteria membrane. Application of an external magnetic field removes MNP from solution sweeping bacteria attached to them. The interaction of the MNP with Gram-positive S. aureus bacteria is more sensible to the size of dendritic system covering the MNP, whereas interaction with Gramnegative E. coli bacteria is more sensible to the density of cationic groups. Over 500 ppm of NPM, MNP covered with dendrons captured over 90% of both type of bacteria, whereas MNP covered with dendrimers were only able to capture S. aureus bacteria (over 90%) but not E. coli bacteria. Modified MNP were characterized by transmission electron microscopy (TEM), thermogravimetric analysis (TGA), Fourier-transform infrared spectroscopy (FTIR), Z potential and dynamic light scattering (DLS). Interaction with bacteria was analyzed by UV, TEM and scanning electron microscopy (SEM). Moreover, the possibility to recycle cationic dendronized MNP was explored.Ministerio de EconomĂa, Industria y CompetitividadComunidad de MadridInstituto RamĂłn y Cajal de InvestigaciĂłn Sanitari
New synthetic procedure for the antiviral sulfonate carbosilane dendrimer G2-S16 and its fluorescein-labelled derivative for biological studies
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).Universidad de AlcaláMinisterio de EconomĂa, Industria y CompetitividadComunidad de MadridInstituto de Salud Carlos IIIJunta de Comunidades de Castilla-La Manch
Effect of PEGylation on the biological properties of cationic carbosilane dendronized gold nanoparticles
Heterofunctionalized gold nanoparticles (AuNPs) were obtained in a one pot reaction of gold precursor with cationic carbosilane dendrons (first to third generations, 1-3G) and (polyethylene)glycol (PEG) ligands in the presence of a reducing agent. The final dendron/PEG proportion on AuNPs depends on the initial dendron/PEG ratio (3/1, 1/1, 1/3) and dendron generation. AuNPs were characterized by transmission electron microscopy (TEM), dynamic light scattering (DLS), ultraviolet spectroscopy (UV-VIS), thermogravimetric analysis (TGA), nuclear magnetic resonance (H-1 NMR) and zeta potential (ZP). Several assays have been carried out to determine the relevance of PEG/dendron ratio and dendron generation in the biomedical properties of PEGylated AuNPs and the results have been compared with those obtained for non-PEGylated AuNPs. Finally, analyses of PEG recognition by anti-PEG antibodies were carried out. In general, haemolysis, platelet aggregation and toxicity were reduced after PEGylation of AuNPs, the effect being dependent on dendron generation and dendron/PEG ratio. Dendron generation determines the exposure of PEG ligand and the interaction of this ligand with AuNPs environment. On the other hand, increasing PEG proportion diminishes toxicity but also favors interaction with antibodies.Ministerio de EconomĂa, Industria y CompetitividadJunta de Comunidades de Castilla-La ManchaComunidad de MadridCentro de investigaciĂłn BiomĂ©dica en Red. Enfermedades BioingenierĂa, Biomateriales y NanomedicinaInstituto RamĂłn y Cajal de InvestigaciĂłn SanitariaUniversidad de Alcal
Role of cationic carbosilane dendrons and metallic core of functionalized gold nanoparticles in their interaction with human serum albumin
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 albuminwas 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