Cationic Carbosilane Research Articles

Study of the antimicrobial activity of cationic carbosilane dendrimers against clinical strains of multidrug-resistant bacteria and their biofilms.

Antimicrobial Resistance is a serious public health problem, which is aggravated by the ability of the microorganisms to form biofilms. Therefore, new therapeutic strategies need to be found, one of them being the use of cationic dendritic systems (dendrimers and dendrons). The aim of this study is to analyze the in vitro antimicrobial efficacy of six cationic carbosilane (CBS) dendrimers and one dendron with peripheral ammonium groups against multidrug-resistant bacteria, some of them isolated hospital strains, and their biofilms. For this purpose, minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), minimum biofilm inhibitory concentration (MBIC) and minimum eradication biofilm concentration (MBEC) studies were carried out. In addition, the cytotoxicity on Hela cells of those compounds that proved to be the most effective was analyzed. All the tested compounds showed in vitro activity against the planktonic forms of methicillin-resistant Staphylococcus aureus and only the dendrimers BDSQ017, BDAC-001 and BDLS-001 and the dendron BDEF-130 against their biofilms. On the other hand, only the dendrimers BDAC 001, BDLS-001 and BDJS-049 and the dendron BDEF-130 were antibacterial in vitro against the planktonic forms of multidrug-resistant Pseudomonas aeruginosa, but they lacked activity against their preformed biofilms. In addition, the dendrimers BDAC-001, BDLS-001 and BDSQ-017 and the dendron BDEF-130 exhibited a good profile of cytotoxicity in vitro. Our study demonstrates the possibility of using the four compounds mentioned above as possible topical antimicrobials against the clinical and reference strains of multidrug-resistant bacteria.

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 Gram-negative 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.

PEGylation of dendronized silver nanoparticles increases the binding affinity of antimicrobial proteins

Antibacterial resistance has become a global threat, and there is a pressing need for new antibacterial agents to treat bacterial infection. Silver nanoparticles (AgNPs) covered with cationic carbosilane (CBS) dendrons are promising nanomaterials thanks to their antibacterial activity and their ability to deliver antibacterial agents like antimicrobial proteins (AMP); lysozyme and bacteriophage endolysin. However, without an understanding and control of the nature of interactions between endolysin and dendronized AgNPs and affinity of serum proteins to NPs surface, the application of this multifunctional system in medicine and biology is limited. Herein, we investigate the interactions of PEGylated and non-PEGylated CBS dendronized AgNPs (PEG-Dend-AgNPs and Dend-AgNPs, respectively) with KP27 endolysin, lysozyme and human serum albumin (HSA) to check the binding mechanism and affinity between the NPs and proteins and the role of the PEG chain on the surface of dendritic silver nanoparticles. Analysis of binding mechanism with thermophoresis, fluorescence, thermodynamics, SPR and adsorption shows that endolysin and lysozyme have a higher affinity for PEG-Dend-AgNPs, whereas HSA has higher affinity to Dend-AgNPs. Lysozyme and endolysin create a monolayer “protein-PEG-Dend-AgNPs” corona and HSA creates a multilayer “protein-Dend-AgNPs”. These phenomena help to us to understand how surface modification is involved in the mechanisms of interaction of dendronized AgNPs with antimicrobial proteins (AMPs).This may help to develop new and better complexes of AMP-dendronized AgNPs acting against resistant bacteria with reduced affinity to serum proteins to improve their antimicrobial properties.