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Krzysztof Sztandera,1 Michał Gorzkiewicz,1,2 Mateusz Bątal,1 Valeria Arkhipova,3,4 Nadezhda Knauer,3,5,6 Javier Sánchez-Nieves,7,8 Fco Javier de la Mata,7– 9 Rafael Gómez,7– 9 Evgeny Apartsin,3,4,10 Barbara Klajnert-Maculewicz1 1Department of General Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, Lodz, 90-236, Poland; 2Department of Molecular Medicine II, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf, 40225, Germany; 3Institute of Chemical Biology and Fundamental Medicine SB RAS, Novosibirsk, 630090, Russia; 4Department of Natural Sciences, Novosibirsk State University, Novosibirsk, 630090, Russia; 5Research Institute of Fundamental and Clinical Immunology, Novosibirsk, 630099, Russia; 6Clinic for Neurosurgery, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf, 40225, Germany; 7Departamento de Química Orgánica y Química Inorgánica, UAH-IQAR, Alcalá de Henares, 28805, Spain; 8Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Madrid, 28029, Spain; 9Instituto Ramón y Cajal de Investigación Sanitaria, IRYCIS, Madrid, 28034, Spain; 10Laboratoire de Chimie de Coordination CNRS, Toulouse, 31077, FranceCorrespondence: Barbara Klajnert-Maculewicz, Department of General Biophysics, Pomorska 141/143, Łódź, 90-236, Poland, Tel +48 42 635 44 29, Fax +48 42 635 4474, Email barbara.klajnert@biol.uni.lodz.plBackground: The search for new formulations for photodynamic therapy is intended to improve the outcome of skin cancer treatment using significantly reduced doses of photosensitizer, thereby avoiding side effects. The incorporation of photosensitizers into nanoassemblies is a versatile way to increase the efficiency and specificity of drug delivery into target cells. Herein, we report the loading of rose bengal into vesicle-like constructs of amphiphilic triazine-carbosilane dendrons (dendrimersomes) as well as biophysical and in vitro characterization of this novel nanosystem.Methods: Using established protocol and analytical and spectroscopy techniques we were able to synthesized dendrons with strictly designed properties. Engaging biophysical methods (hydrodynamic diameter and zeta potential measurements, analysis of spectral properties, transmission electron microscopy) we confirmed assembling of our nanosystem. A set of in vitro techniques was used for determination ROS generation, (ABDA and H2DCFDA probes), cell viability (MTT assay) and cellular uptake (flow cytometry and confocal microscopy).Results: Encapsulation of rose bengal inside dendrimersomes enhances cellular uptake, intracellular ROS production and concequently, the phototoxicity of this photosensitizer.Conclusion: Triazine-carbosilane dendrimersomes show high capacity as drug carriers for anticancer photodynamic therapy.Graphical Abstract: Keywords: dendrons, amphiphiles, carbosilane, photodynamic therapy, rose bengal, dendrimersomes

Gold nanoparticles (AuNPs) are potentially applicable in drug/nucleic acid delivery systems. Low toxicity, high stability, and bioavailability are crucial for the therapeutic use of AuNPs and they are mainly determined by their interactions with proteins and lipids on their route to the target cells. In this work, we investigated the interaction of two pegylated gold nanoparticles, AuNP14a and AuNP14b, with human serum proteins albumin (HSA) and transferrin (Tf) as well as dimyristoyl-phosphatidylcholine (DMPC) liposomes, which can be a representative of biomembranes. We showed that AuNP14a/b interacted with HSA and Tf changing their electrical, thermodynamic, and structural properties as evidenced by dynamic light scattering, zeta potential, transmission electron microscopy, circular dichroism, fluorescence quenching, and isothermal titration calorimetry. These nanoparticles penetrated the DMPC membrane suggesting their ability to reach a target inside the cell. In most of the effects, AuNP14b was more effective than AuNP14a, which might result from its more positive charge. Further studies are needed to evaluate whether the interaction of AuNP14a/b with HSA and Tf is safe for the cell/organism and whether they may safely penetrate natural membranes., (© 2024. The Author(s).)

Introduction: 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)., Methods: 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., Results: 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 ., Discussion: 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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Hernando-Gozalo, Aguilera-Correa, Rescalvo-Casas, Seijas-Pereda, García-Bertolín, de la Mata, Sánchez-Nieves, Cuadros and Pérez-Tanoira.)

The development of biofilms on different surfaces continues to be a major public health problem. The antimicrobial resistance and the difficulty of finding drugs capable of combating these established biofilms generates the urgent need to find compounds that prevent cells from settling and establishing of these complex communities of microorganisms. Zwitterionic modification of nanomaterials allows the formation of a hydration layer, and this highly hydrophilic surface provides antifouling properties as well as a good biocompatibility by preventing non-specific interactions. Thus, they are appropriate candidates to prevent microbial adhesion to different surfaces and, in consequence, avoid biofilm formation. For this reason, we have incorporated zwitterionic moieties in multivalent systems, as are carbosilane dendrimers. Characterization of these systems was performed using nuclear magnetic resonance and mass spectrometry. It has been analysed if the new molecules have capacity to inhibit the biofilm formation in Candida albicans, Staphylococcus aureus and Pseudomonas aeruginosa. The results showed that they were more effective against S. aureus, observing a biofilm reduction of 81.5% treating with 32 mg/L of G2SiZWsf dendrimer and by 72.5% using 32 mg/L of the G3SiZWsf dendrimer. Finally, the absence of cytotoxicity was verified by haemolysis and cytotoxicity studies in human cells lines., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Dendrimers are multifunctional molecules with well-defined size and structure due to the step-by-step synthetic procedures required in their preparation. Dendritic constructs based on carbosilane scaffolds present carbon-carbon and carbon-silicon bonds, which results in stable, lipophilic, inert, and flexible structures. These properties are highly appreciated in different areas, including the pharmaceutical field, as they can increase the interaction with cell membranes and improve the therapeutic action. This article summarizes the most recent advances in the pharmaceutical applications of carbosilane dendritic molecules, from therapeutics to diagnostics and prevention tools. Dendrimers decorated with cationic, anionic, or other moieties, including metallodendrimers; supramolecular assemblies; dendronized nanoparticles and surfaces; as well as dendritic networks like hydrogels are described. The collected examples confirm the potential of carbosilane dendrimers and dendritic materials as antiviral or antibacterial agents; in therapy against cancer, neurodegenerative disease, or oxidative stress; or many other biomedical applications. This article is categorized under: Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Therapeutic Approaches and Drug Discovery > Nanomedicine for Infectious Disease Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease., (© 2022 The Authors. WIREs Nanomedicine and Nanobiotechnology published by Wiley Periodicals LLC.)

Enzyme immobilization is a powerful strategy for enzyme stabilization and recyclability. Materials covered with multipoint molecules are very attractive for this goal, since the number of active moieties to attach the enzyme increases with respect to monofunctional linkers. This work evaluates different dendrimers supported on silica to immobilize a protease enzyme, Alcalase. Five different dendrimers were employed: two carbosilane (CBS) dendrimers of different generations (SiO 2 -G 0 Si-NH 2 and SiO 2 -G 1 Si-NH 2 ), a CBS dendrimer with a polyphenoxo core (SiO 2 -G 1 O 3 -NH 2 ), and two commercial polyamidoamine (PAMAM) dendrimers of different generations (SiO 2 -G 0 PAMAM-NH 2 and SiO 2 -G 1 PAMAM-NH 2 ). The results were compared with a silica support modified with a monofunctional molecule (2-aminoethanethiol). The effect of the dendrimer generation, the immobilization conditions (immobilization time, Alcalase/SiO 2 ratio, and presence of Ca 2+ ions), and the digestion conditions (temperature, time, amount of support, and stirring speed) on Alcalase activity has been evaluated. Enzyme immobilization and its activity were highly affected by the kind of dendrimer and its generation, observing the most favorable behavior with SiO 2 -G 0 PAMAM-NH 2 . The enzyme immobilized on this support was used in two consecutive digestions and, unlike CBS supports, it did not retain peptides released in the digestion.

The search for new microbicide compounds is of an urgent need, especially against difficult-to-eradicate biofilm-forming bacteria. One attractive option is the application of cationic multivalent dendrimers as antibacterials and also as carriers of active molecules. These compounds require an adequate hydrophilic/hydrophobic structural balance to maximize the effect. Herein, we evaluated the antimicrobial activity of cationic carbosilane (CBS) dendrimers unmodified or modified with polyethylene glycol (PEG) units, against planktonic and biofilm-forming P. aeruginosa culture. Our study revealed that the presence of PEG destabilized the hydrophilic/hydrophobic balance but reduced the antibacterial activity measured by microbiological cultivation methods, laser interferometry and fluorescence microscopy. On the other hand, the activity can be improved by the combination of the CBS dendrimers with endolysin, a bacteriophage-encoded peptidoglycan hydrolase. This enzyme applied in the absence of the cationic CBS dendrimers is ineffective against Gram-negative bacteria because of the protective outer membrane shield. However, the endolysin-CBS dendrimer mixture enables the penetration through the membrane and then deterioration of the peptidoglycan layer, providing a synergic antimicrobial effect.

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., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

The use of nonviral carriers based on nanomaterials is a promising strategy for modern gene therapy aimed at protecting the genetic material against degradation and enabling its efficient cellular uptake. To improve the effectiveness of nanocarriers in vivo , they are often modified with poly(ethylene glycol) (PEG) to reduce their toxicity, limit nonspecific binding by proteins in the bloodstream, and extend blood half-life. Thus, the selection of an appropriate degree of surface PEGylation is crucial to preserve the interaction of nanoparticles with the genetic material and to ensure its efficient transport to the site of action. Our research focuses on the use of innovative gold nanoparticles (AuNPs) coated with cationic carbosilane dendrons as carriers of siRNA. In this study, using dynamic light scattering and zeta potential measurements, circular dichroism, and gel electrophoresis, we investigated dendronized AuNPs modified to varying degrees with PEG in terms of their interactions with siRNA and thrombin to select the most promising PEGylated carrier for further research.

This work evaluates different dendrimer-silica supports for the immobilization of enzymes by multipoint covalent binding. Thermolysin was immobilized on two dendrimers (PAMAM and carbosilane) with two different generations (zero (G0) and first (G1)). Results were compared with a control, a silica support functionalized with a monofunctional molecule. Dendrimers increased the number of available sites to bind the enzyme. Despite the enzyme was immobilized on all supports, G0 dendrimers immobilized a 30% more enzyme than G1. Thermolysin immobilized on G0 dendrimer supports showed the highest activity and could be employed in three consecutive hydrolysis cycles. Optimal immobilization time was 1 h while optimal protein loading was 25 mg enzyme/100 mg support. Enzyme activity was promoted when using 5 mg of immobilized enzyme at 750 rpm, 60 °C, and 2 h of hydrolysis. Under these conditions, the activity of thermolysin increased up to the 78% of the free enzyme activity. Kinetics of the hydrolysis reaction using the immobilized thermolysin was also studied and compared with the obtained using the free thermolysin. The addition of ZnCl 2 and NaCl during the immobilization procedure increased thermolysin activity in the second (22% more) and in the third (14% more) hydrolysis clycles., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Antibodies are macromolecules that specifically recognize their target, making them good candidates to be employed in various therapies. The possibility of attaching a drug to an immunoglobulin makes it possible to release it specifically into the affected tissue as long as it overexpresses the target. However, chemical coupling could affect the functionality (specificity and affinity) of the antibody. It has been observed that the use of intermediaries, such as dendrimers, could resolve this issue. Because carbosilane dendrimers have aroused great interest in the field of biomedicine, this report describes the synthesis of an anionic carbosilane dendrimer with a fluorochrome on its surface that then forms a conjugate with an antibody. It has been used as immunoglobulin and infliximab, whose target is TNF-α, which is a cytokine that is overexpressed in the inflamed area or even in the blood of patients with autoimmune diseases, such as rheumatoid arthritis. In addition, the integrity and functionality of the antibody has been studied to see if they have been affected after the chemical coupling process.

The transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) is considered as the master regulator of antioxidant and cytoprotective gene expressions. Moreover, it plays a pivotal role in cancer progression. Nrf2 mediates the adaptive response which contributes to the resistance to chemotherapeutic pro-oxidant drugs, such as cisplatin (CDDP), in various tumors, including bladder cancers. For this reason, Nrf2 could be a promising target to overcome chemoresistance. There are several known Nrf2 pharmacological inhibitors; however, most of them are not specific. The use of a specific small interfering RNA (siRNA) targeting the Nrf2 gene (siNrf2) loaded into nanovehicles is an attractive alternative, since it can increase specificity. This study aimed to evaluate the biological activity of siNrf2 loaded on guanidine-terminated carbosilane dendrimers (GCDs) in overcoming CDDP resistance in bladder cancer cells with a high level of Nrf2. Parameters such as viability, proliferation, apoptosis, migration, and oxidative stress level were taken into account. Results demonstrated that siNrf2-GCD treatment sensitized CDDP-resistant cells to CDDP treatment. Moreover, data obtained by treating the non-cancerous human kidney HK-2 cell line strongly suggest a good safety profile of the carbosilane dendrimers loaded with siNrf2. In conclusion, we suggest that siNrf2-GCD is a promising drug delivery system for gene therapy to be used in vivo; and it may represent an important tool in the therapy of CDDP-resistant cancer.

Candida spp. are one of the most common fungal pathogens. Biofilms formed by Candida albicans offer resistance mechanisms against most antifungal agents. Therefore, development of new molecules effective against these microorganisms, alone or in combination with antifungal drugs, is extremely necessary. In the present work, we carried out a screening process of different cationic carbosilane dendritic molecules against C. albicans . In vitro activity against biofilm formation and biofilms was tested in both Colección Española de Cultivos Tipo (CECT) 1002 and clinical C. albicans strains. Cytotoxicity was studied in human cell lines, and biofilm alterations were observed by scanning electron microscopy (SEM). Antifungal activity of the carbosilane dendritic molecules was assessed by monitoring cell viability using both established and novel cell viability assays. One out of 14 dendritic molecules tested, named BDSQ024, showed the highest activity with a minimum biofilm inhibitory concentration (MBIC) for biofilm formation and a minimum biofilm damaging concentration (MBDC) for existing biofilm of 16-32 and 16 mg/L, respectively. Synergy with amphotericin (AmB) and caspofungin (CSF) at non-cytotoxic concentrations was found. Therefore, dendritic compounds are exciting new antifungals effective at preventing Candida biofilm formation and represent a potential novel therapeutic agent for treatment of C. albicans infection in combination with existing clinical antifungals.

Supramolecular constructions of amphiphilic dendritic molecules are promising vehicles for anti-cancer drug delivery due to the flexibility of their architecture, high drug loading capacity and avoiding off-target effects of a drug. Herein, we report a new class of amphiphilic dendritic species-triazine-carbosilane dendrons readily self-assembling into pH-sensitive dendrimersomes. The dendrimersomes efficiently encapsulate anticancer drugs doxorubicin and methotrexate. Chemodrug-loaded dendrimersomes have dose-related cytotoxic activity against leukaemia cell lines 1301 and K562. Our findings suggest that triazine-carbosilane dendrimersomes are prospective drug carriers for anti-cancer therapy.

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., Competing Interests: The authors declare no conflict of interest.

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 (C 2 H 3 SO 3 F, 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)., Competing Interests: There are no conflicts of interest to declare., (This journal is © The Royal Society of Chemistry.)

Materials modified with ammonium groups on the surface have shown antibacterial activity. In this paper, alkyl chains, carbosilane (CBS) dendrimers and dendrons and poly(amidoamine) (PAMAM) dendrimers containing amine and ammonium groups have been grafted to silica surface and the influence of molecule structure on the stability and on antibacterial activity have been evaluated. These materials have been characterized by thermogravimetric analysis (TGA), zeta (Z) potential, scanning electron microscopy (SEM), infrared spectroscopy (IR) and nuclear magnetic resonance ( 13 C CP MAS NMR). The degree of silica functionalization depends on type of outer groups, amine or ammonium, type and core of dendrimer, and length of chains. The Z potential measurements of these materials in water suspensions were used to test their stability in this medium. These measurements showed, for some of the modified silicas, the diminishing of Z potential from positive values toward zero, probably due to interaction of the functional groups with the silica surface. This variation was also dependent on ligand structure and peripheral functions. Finally, studies of inhibition of bacteria growth stand out again the relevance of ligand structure and number of functional groups on silica surface. The most active systems were those with more surface covered, those with cationic groups further away from silica surface and higher dendritic generation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Protein sample preparation is the bottleneck in the analysis of proteins. The aim of this work is to evaluate the feasibility of carbosilane dendrimers functionalized with cationic groups to make easier this step. Anionic carbosilane dendrimers (sulphonate- and carboxylate-terminated) have already demonstrated their interaction with proteins and their potential in protein sample preparation. In this work, interactions between positively charged carbosilane dendrimers and different model proteins were studied when working under different pH conditions, dendrimer concentrations, and dendrimer generations. Amino- and trimethylammonium-terminated carbosilane dendrimers presented, in some cases, weak interactions with proteins. Unlike them, carbosilane dendrimers with terminal dimethylamino groups could interact, in many cases, with proteins and these interactions were affected by the pH, the dendrimer concentration, and the dendrimer generation. Moreover, dendrimer precipitation was observed at all pHs, although just second and fourth generation (2 G and 4 G) dendrimers resulted in the formation of complexes with proteins. Under experimental conditions promoting dendrimer-protein interactions, 2 G dimethylamino-terminated dendrimers were proposed as an alternative to other methods used in analytical chemistry or analysis in which an organic solvent or a resin are required to enrich/purify proteins in a complex sample., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2019 Elsevier B.V. All rights reserved.)

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 ( 1 H 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., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Antimicrobial proteins, like lysozymes produced by animals or bacteriophage lysins, enable the degradation of bacterial peptidoglycan (PG) and, consequently, lead to bacterial cell lysis. However, the activity of those enzymes is not satisfactory against gram-negative bacteria because of the presence of an outer membrane (OM) barrier. Lytic enzymes can therefore be combined with membrane-disrupting agents, such as dendritic silver nanoparticles. Nevertheless, a lipopolysaccharide (LPS), especially the smooth type, could be the main hindrance for highly charged nanoparticles to get direct access to the bacterial OM and to help lytic enzymes to reach their target PG. Herein, we have investigated the interactions of PEGylated carbosilane dendritic nanoparticles with P. aeruginosa 010 LPS in the presence of lysozymes and KP27 endolysin to find out the main aspects of the OM destabilization process. Our results showed that PEGylated dendronized AgNPs overcame the LPS barrier and enhanced the antibacterial effect of endolysin more efficiently than unPEGylated nanoparticles., (Copyright © 2019 Ciepluch, Skrzyniarz, Barrios-Gumiel, Quintana, Sánchez-Nieves, de la Mata, Maciejewska, Drulis-Kawa and Arabski.)

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.

The interaction of neuropeptides, vasoactive intestinal peptide (VIP), or growth hormone-releasing hormone (GHRH), with a cationic carbosilane dendrimer forms dendriplexes with antitumoral behavior in advanced prostate cancer cells PC3. At the concentrations used for dendriplexes formation, the free peptides were protumoral and prometastatic in advanced prostate cancer, while dendrimer only showed low cytotoxicity, but did not avoid the metastatic behavior of PC3 cells. However, these nanoplexes favored also cell adhesion and avoided cell migration. Also, the dendriplexes were not toxic for no tumoral prostate cells (RPWE-1) or fibroblasts. The use of labeled GHRH peptide (rhodamine labeled) and a dendrimer (fluorescein labeled) allowed us to observe that both systems reach the intracellular milieu after dendriplex formation. The treatment of PC3 cells with the nanoplexes reduced expression of vascular endothelial growth factor (VEGF) and cyclic adenosine monophosphate (cAMP). Molecular modeling analysis highlights the important contribution of the carbosilane framework in the stabilization of the dendriplex, since dendrimer interacts with a peptide region where hydrophobic amino acids are presented.

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., (Copyright © 2017 Elsevier B.V. All rights reserved.)

The interaction of a double stranded small interference RNA (siRNA Nef) with cationic carbosilane dendrimers of generations 1-3 with two different ammonium functions at the periphery ([-NMe 2 R] + , R=Me, (CH 2 ) 2 OH) has been studied by experimental techniques (zeta potential, electrophoresis, single molecule pulling experiments) and molecular dynamic calculations. These studies state the presence of different forces on dendriplex formation, depending on generation and type of ammonium group. Whilst for higher dendrimers electrostatic forces mainly drive the stability of dendriplexes, first generation compounds can penetrate into siRNA strands due to the establishment of hydrophobic interactions. Finally, in the particular case of first generation dendrimer [G 1 O 3 (NMe 2 (CH 2 ) 2 OH)) 6 ] 6+ ; the presence of hydroxyl groups reinforces dendriplex stability by hydrogen bonds formation. However, since these small dendrimers do not cover the RNA, only higher generation derivatives protect RNA from degradation., (Copyright © 2017 Elsevier B.V. All rights reserved.)

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., (Copyright © 2017 Elsevier B.V. All rights reserved.)

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 1 H 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).

In order to improve the efficiency of the anti-inflammatory drug ibuprofen, cationic carbosilane dendrimers and dendrons with ibuprofen at their periphery or at their focal point, respectively, have been synthesized, and the release of the drug was studied using HPLC. Macrophages were used to evaluate the anti-inflammatory effect of the ibuprofen-conjugated dendritic systems and compared with mixtures of non-ibuprofen dendritic systems in the presence of the drug. The cationic ibuprofen-conjugated dendron was the compound that showed higher anti-inflammatory properties. It reduces the LPS-induced COX-2 expression and decreases the release of several inflammatory cytokines such as TNFα, IL-1β, IL-6, and CCL3. These results open new perspectives in the use of these compounds as drug carriers.

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., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

A novel nanosystem based on mesoporous silica nanoparticles covered with carbosilane dendrons grafted on the external surface of the nanoparticles is reported. This system is able to transport single-stranded oligonucleotide into cells, avoiding an electrostatic repulsion between the cell membrane and the negatively charged nucleic acids thanks to the cationic charge provided by the dendron coating under physiological conditions. Moreover, the presence of the highly ordered pore network inside the silica matrix would make possible to allocate other therapeutic agents within the mesopores with the aim of achieving a double delivery. First, carbosilane dendrons of second and third generation possessing ammonium or tertiary amine groups as peripheral functional groups were prepared. Hence, different strategies were tested in order to obtain their suitable grafting on the outer surface of the nanoparticles. As nucleic acid model, a single-stranded DNA oligonucleotide tagged with a fluorescent Cy3 moiety was used to evaluate the DNA adsorption capacity. The hybrid material functionalised with the third generation of a neutral dendron showed excellent DNA binding properties. Finally, the cytotoxicity as well as the capability to deliver DNA into cells, was tested in vitro by using a human osteoblast-like cell line, achieving good levels of internalisation of the vector DNA/carbosilane dendron-functionalised material without affecting the cellular viability., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Nanotechnology offers a new platform for therapeutic delivery of antiretrovirals to the central nervous system (CNS). Nanoformulated antiretroviral drugs offer multifunctionality, that is, the ability to package multiple diagnostic and therapeutic agents in the same nanocompose, along with the added provisions of site-directed delivery, delivery across the blood-brain-barrier (BBB), and controlled release of therapeutics. We studied the viability of dendrimers and dendriplexes in human primary astrocytes, as well as their uptake by these astrocytes. Functional validation was performed by using specific siRNA against HIV-1 Nef to interfere to HIV-1 infectivity. A high efficiency in Nef silencing, reducing HIV-1 infectivity was observed in astrocytes treated with dendriplexes compared with control or siRandom treated astrocytes. More interestingly, we studied the biodistribution of the second generation of carbosilane dendrimer loaded with FITC (2G-(SNMe3I)11-FITC) in vivo, in BALB/c mice. Dendriplexes were inoculated into BALB/c mice by the retro-orbital venous plexus, and their localization was determined after 1 and 24h post-injection. Dendriplexes were detected inside the brain by a sensitive imaging system of fluorescent imaging in vivo (IVIS Lumina), and by confocal microscopy analysis of sections of OCT-embedded tissues. The 2G-(SNMe3I)11-FITC dendrimer transported efficiently siRNA into the brain, crossing the BBB. Moreover, this dendrimer successfully delivered and transfected siRNA to HIV-infected human primary astrocytes and achieved gene silencing without causing cytotoxicity. These results highlight the potential of this nanoformulation in the treatment of neurological disorders., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Here we synthesized carbosilane, generation 1 to 3, and PEG-based dendrons functionalized at the periphery with NHBoc groups and at the focal point with azide and alkyne moieties, respectively. The coupling of these two types of dendrons via click chemistry led to the formation of new hybrid dendrimers with two distinct moieties, the hydrophobic carbosilane and the hydrophilic PEG-based dendron. The protected dendrimers were transformed into cationic ammonium dendrimers. These unique amphiphilic dendrimers were studied as vectors for gene therapy against HIV in peripheral blood mononuclear cells (PBMC) and their performance was compared with that of a PEG-free carbosilane dendrimer. The presence of the PEG moiety afforded lower toxicities and evidenced a weaker interaction between dendrimers and siRNA when compared to the homodendrimer analogous. Both features, lower toxicity and lower dendriplex strength, are key properties for use of these vectors as carriers of nucleic material., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

Treatment of HIV infection by gene therapy is a promising tool for combating AIDS. One of the primary limitations of gene therapy is the effective delivery of nucleic acids to the target cells. Dendrimers are nanoparticles that are increasingly being used as nucleic acid vehicles. We have synthesized "Si-C" amino-terminated carbosilane dendrimers [GnO3(NMe3)m](m+) functionalized with quaternary ammonium (NMe3(+)) terminal groups via hydrosilylation of allyl dimethylamine with the corresponding GnO3(SiH)m dendrimers and further addition of MeI. These dendrimers are soluble in water. Initially, complexation between these "Si-C" dendrimers and anti-HIV nucleic acids (oligodeoxynucleotides ANTITAR and GEM91, siRNA siP24) was studied and molar ratios for complete complexation were determined. Then the charge and size of the dendriplexes (complexes of "Si-C" dendrimers with nucleic acids) were analyzed and it was found that they possessed charges of +5 to +40 mV and sizes of 60-600 nm (zeta-size) or 50-100 nm (atomic force microscopy) suitable for cell transfection. Stability studies showed that the dendriplexes were stable over time and were resistant to degradation by serum albumin. The effects of dendrimers and their dendriplexes on erythrocytes (isolated and in whole blood) revealed that the dendriplexes were significantly less cytotoxic than the pure dendrimers. The effects of dendrimers and their dendriplexes on peripheral blood mononuclear cells (the main target of HIV) were analyzed and it was found that the dendriplexes were 10 times less cytotoxic than the pure dendrimers. Finally, transfection experiments revealed that "Si-C"-carbosilane dendrimers had a restricted ability to deliver long-chain double-stranded nucleic acids. The results indicate that these cationic carbosilane dendrimers are good candidates for delivering short-chain siRNA and oligodeoxynucleotide to HIV-infected peripheral blood mononuclear cells or lymphocytes., (Copyright © 2013 Elsevier B.V. All rights reserved.)

This paper examines the formation and stability of nano-complexes that could provide a new therapeutic approach against HIV-1 infection. Poly(propylene imine) glycodendrimers decorated with 2(nd) generation cationic carbosilane dendrons were generated and their use in polyplex formation checked. Owing to their positively-charged terminal amino groups the hybrid glycodendrimers can bind anionic peptides. It was shown that they form nano-complexes with the HIV-derived peptides P24, Gp160 and Nef. Complexes 130-190 nm in size were formed in molar ratios (dendrimer/ peptide) of (3-4):1. These were sufficiently stable over time and at different pHs. The results obtained suggest that the hybrid dendrimers studied can be considered as alternative carriers for delivering HIV peptides to dendritic cells.

Anionic carbosilane dendrimers of generations 1-3 have been synthesized containing carboxylate G(n)X(C(2)H(4)CO(2)Na)(m) and sulfonate G(n)X(C(2)H(4)SO(3)Na)(m) peripheral groups and derived from two different cores, 1,3,5-(HO)(3)C(6)H(3) (X = O(3)) and Si(C(3)H(5))(4) (X = Si). The peripheral anionic groups make these dendrimers water soluble, despite their highly hydrophobic framework. These dendrimers present a net negative charge in water, which was influenced by the pH of the medium. This characteristic was studied by pH titration. Also molecular modeling calculations have been performed to study differences in an aqueous medium between carboxylate and sulfonate dendrimers of different cores. The results obtained were also compared with those obtained from DOSY NMR experiments and zeta-potential measurements.

A new family of amine- and ammonium-terminated hyperbranched polycarbosilanes (PCS) and dendrimers has been synthesized. The functionalization of a polycarbosilane matrix was carried out with peripheral allyl groups by two strategies in the case of PCS: 1) hydrosilylation of allyl amines with PCS containing terminal Si-H bonds, or 2) hydrosilylation of PCS-allyl with an aminosilane. Dendrimers with terminal amine groups were synthesized by hydrosilylation of allydimethylamine. Quaternized systems with MeI are soluble and stable in water or other protic solvent. The antibacterial properties of the ammonium-terminated hyperbranched polycarbosilanes and dendrimers have been evaluated showing that they act as potent biocides against Gram-positive and Gram-negative bacterial strains.

Hydrolysis of [NbCp'Cl(4)] (Cp' = η(5)-C(5)H(4)SiMe(3)) with the water adduct H(2)O·B(C(6)F(5))(3) afforded the oxo-borane compound [NbCp'Cl(2){O·B(C(6)F(5))(3)}] (2a). This compound reacted with [MgBz(2)(THF)(2)] giving [NbCp'Bz(2){O·B(C(6)F(5))(3)}] (2b), whereas [NbCp'Me(2){O·B(C(6)F(5))(3)}] (2c) was obtained from the reaction of [NbCp'Me(4)] with H(2)O·B(C(6)F(5))(3). Addition of Al(C(6)F(5))(3) to solutions containing the oxo-borane compounds [MCp(R)X(2){O·B(C(6)F(5))(3)}] (M = Ta, Cp(R) = η(5)-C(5)Me(5) (Cp*), X = Cl 1a, Bz 1b, Me 1c; M = Nb, Cp(R) = Cp', X = Cl 2a) afforded the oxo-alane complexes [MCp(R)X(2){O·Al(C(6)F(5))(3)}] (M = Ta, Cp(R) = Cp*, X = Cl 3a, Bz 3b, Me 3c; M = Nb, Cp(R) = Cp', X = Cl 4a), releasing B(C(6)F(5))(3). Compound 3a was also obtained by addition of Al(C(6)F(5))(3) to the dinuclear μ-oxo compound [TaCp*Cl(2)(μ-O)](2), meanwhile addition of the water adduct H(2)O·Al(C(6)F(5))(3) to [TaCp*Me(4)] gave complex 3c. The structure of 2a and 3a was obtained by X-ray diffraction studies. Density functional theory (DFT) calculations were carried out to further understand these types of oxo compounds.

The dinuclear dialkoxo-bridged complexes [(TiCl)(2)(mu-O(2)L)(mu-{(eta(5)-C(5)Me(4)SiMeO)(2)(mu-O)})] (O(2)L = 1,2-O(2)C(2)H(4), 1,2-O(2)C(6)H(4), 1,2-(OCH(2))(2)C(6)H(4), O(2)SiPh(2)) were obtained by reaction of [(TiCl(2))(2)(mu-{(eta(5)-C(5)Me(4)SiMeO)(2)(mu-O)})] () with the corresponding dilithium salt () or diol (, , ). Alkylation of and with ClRMg afforded [(TiR)(2)(mu-O(2)L)(mu-{(eta(5)-C(5)Me(4)SiMeO)(2)(mu-O)})] (O(2)L = 1,2-O(2)C(2)H(4), R = Me , Bz ; O(2)L = 1,2-O(2)C(6)H(4), R = Me , Bz ). Addition of four equiv. of LiOiPr to afforded [{Ti(OiPr)(2)}(2)(mu-{(eta(5)-C(5)Me(4)SiMeO)(2)(mu-O)})] (). Reaction of with Al(C(6)F(5))(3) produced the elimination of the dialkoxo ligand to give [{TiCl(C(6)F(5))}(2)(mu-{(eta(5)-C(5)Me(4)SiMeO)(2)(mu-O)})] (), whereas the same reaction of with Al(C(6)F(5))(3) produced the oxo-alane adduct [(TiCl)(2)(mu-O(2)L)(mu-{(eta(5)-C(5)Me(4)SiMeO)(2)(mu-O.Al{C(6)F(5)}(3))})] (O(2)L = 1,2-O(2)C(6)H(4)) which was further transformed to give a mixture of and [(TiCl){Ti(C(6)F(5))}(mu-O(2)L)(mu-{(eta(5)-C(5)Me(4)SiMeO)(2)(mu-O)})] (O(2)L = 1,2-O(2)C(6)H(4)). One benzyl group of complexes was abstracted with E(C(6)F(5))(3) (E = B, Al) to give the monoionic compounds [Ti(TiBz)(mu-O(2)L)(mu-{(eta(5)-C(5)Me(4)SiMeO)(2)(mu-O)})][BzE(C(6)F(5))(3)] (O(2)L = 1,2-O(2)C(2)H(4), E = B , Al ; O(2)L = 1,2-O(2)C(6)H(4), E = B ), although was unstable in CD(2)Cl(2) evolving to a mixture of compounds where [(TiBz)(2)(mu-Cl)(mu-{(eta(5)-C(5)Me(4)SiMeO)(2)(mu-O)})][BzAl(C(6)F(5))(3)] () was identified, and compound was also unstable at ambient temperature. Polymerization of epsilon-caprolactone was only achieved with the tetraalkoxo compound . All of these complexes were characterized by NMR spectroscopy and , and by X-ray diffraction studies.

The terminal chloroaminophosphido complex [Co(CO)3(PPh3){P(Cl)NiPr2}] is formed via reaction of K[Co(CO)4] with iPr2NPCl2 in the presence of triphenylphosphine. Chloride abstraction by aluminum trichloride leads to the first terminal phosphinidene complex of cobalt, [Co(CO)3(PPh3)(PNiPr2)][AlCl4]. The electrophilicity of the phosphinidene was demonstrated by its reaction with diphenylacetylene to form the phosphirene complex [Co(CO)3(PPh3){P(NiPr2)C(Ph)C(Ph)}][AlCl4].