Amoebicidal and cysticidal in vitro activity of cationic dendritic molecules against Acanthamoeba polyphaga and Acanthamoeba griffini.

Acanthamoeba species are responsible for serious human infections, including Acanthamoeba keratitis (AK) and granulomatous amoebic encephalitis (GAE). These pathogens have a simple life cycle consisting of an infective trophozoite stage and a resistant cyst stage, with cysts posing significant treatment challenges due to their resilience against harsh conditions and chemical agents. Current treatments for AK often involve combining diamines, such as propamidine, and biguanides, such as chlorhexidine (CLX), which exhibit limited efficacy and significant toxicity.

Pegylated gold nanoparticles interact with lipid bilayer and human serum albumin and transferrin.

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.

Effect of polyphenolic dendrimers on biological and artificial lipid membranes.

The use of dendrimers as nanovectors for nucleic acids or drugs requires the understanding of their interaction with biological membranes. This study investigates the impact of 1st generation polyphenolic carbosilane dendrimers on biological and model lipid membranes using several biophysical methods. While the increase in the z-average size of DMPC/DPPG liposomes correlated with the number of caffeic acid residues included in the dendrimer structure, dendrimers that contained polyethylene glycol chains generated lower zeta potential when interacting with a liposomal membrane.

The repertoire of iron superoxide dismutases from as targets in the search for therapeutic agents against leishmaniasis.

Species of and genera are the causative agents of relevant parasitic diseases. Survival inside their hosts requires the existence of a potent antioxidant enzymatic machinery. Four iron superoxide dismutases have been described in trypanosomatids (FeSODA, FeSODB1, FeSODB2, and FeSODC) that hold a potential as therapeutic targets.

Polyphenolic dendrimers as carriers of anticancer siRNA.

Dendrimers have emerged as an important group of nanoparticles to transport drugs, DNA, or RNA into target cells in cancer and other diseases. Various functional modifications can be imposed on dendrimers to increase the efficacy and specificity in delivering their cargo to the target cells and decrease their toxicity. In the present work, we evaluated the potential of carbosilane polyphenolic dendrimers modified with caffeic acid (CA) and polyethylene glycol (PEG) to deliver proapoptotic Mcl-1 and Bcl-2 siRNAs to A549 cancer cells.

Fine-Tuning the Amphiphilic Properties of Carbosilane Dendritic Networks towards High-Swelling Thermogels.

Dendritic hydrogels based on carbosilane crosslinkers are promising drug delivery systems, as their amphiphilic nature improves the compatibility with poorly water-soluble drugs. In this work, we explored the impact of the complementary polymer on the amphiphilic properties of the dendritic network. Different polymers were selected as precursors, from the highly lipophilic propylene glycol (PPG) to the hydrophilic polyethylene glycol (PEG), including amphiphilic Pluronics L31, L35 and L61.

Zinc(II) Iminopyridine Complexes as Antibacterial Agents: A Structure-to-Activity Study.

Antibiotic resistance is currently a global health emergency. Metallodrugs, especially metal coordination complexes, comprise a broad variety of candidates to combat antibacterial infections. In this work, we designed a new family of Schiff base zinc(II) complexes with iminopyridine as an organic ligand and different inorganic ligands: chloride, nitrate, and acetate.

A new class of polyphenolic carbosilane dendrimers binds human serum albumin in a structure-dependent fashion.

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.

Synthesis and biophysical evaluation of carbosilane dendrimers as therapeutic siRNA carriers.

Gene therapy presents an innovative approach to the treatment of previously incurable diseases. The advancement of research in the field of nanotechnology has the potential to overcome the current limitations and challenges of conventional therapy methods, and therefore to unlocking the full potential of dendrimers for use in the gene therapy of neurodegenerative disorders. The blood-brain barrier (BBB) poses a significant challenge when delivering therapeutic agents to the central nervous system.

Bifunctional Carbosilane Dendrimers for the Design of Multipurpose Hydrogels with Antibacterial Action.

The emergence of antibiotic resistance is a serious global health problem. There is an incessant demand for new antimicrobial drugs and materials that can address this global issue from different angles. Dendritic hydrogels have appeared as a promising strategy.

Ruthenium metallodendrimer against triple-negative breast cancer in mice.

Carbosilane metallodendrimers, based on the arene Ru(II) complex (CRD13) and integrated to imino-pyridine surface groups have been investigated as an anticancer agent in a mouse model with triple-negative breast cancer. The dendrimer entered into the cells efficiently, and exhibited selective toxicity for 4T1 cells. In vivo investigations proved that a local injection of CRD13 caused a reduction of tumour mass and was non-toxic.

Lipid-coated ruthenium dendrimer conjugated with doxorubicin in anti-cancer drug delivery: Introducing protocols.

One of the major limitations for the treatment of many diseases is an inability of drugs to cross the cell membrane barrier. Different kinds of carriers are being investigated to improve drug bioavailability. Among them, lipid or polymer-based systems are of special interest due to their biocompatibility.

Amphiphilic Dendritic Hydrogels with Carbosilane Nanodomains: Preparation and Characterization as Drug Delivery Systems.

Carbosilane dendrimers are hyperbranched lipophilic scaffolds widely explored in biomedical applications. This work exploits, for the first time, the ability of these scaffolds to generate functional hydrogels with amphiphilic properties. The monodispersity and multivalency enable a precise synthetic control of the network, while the lipophilicity improves the compatibility with poorly soluble cargo.

Pegylated Gold Nanoparticles Conjugated with siRNA: Complexes Formation and Cytotoxicity.

Drug delivery systems such as dendrimers, liposomes, polymers or gold/silver nanoparticles could be used to advance modern medicine. One significant pharmacological problem is crossing biological barriers by commonly used drugs, e.g.

Combination of Copper Metallodendrimers with Conventional Antitumor Drugs to Combat Cancer in In Vitro Models.

Copper carbosilane metallodendrimers containing chloride ligands and nitrate ligands were mixed with commercially available conventional anticancer drugs, doxorubicin, methotrexate and 5-fluorouracil, for a possible therapeutic system. To verify the hypothesis that copper metallodendrimers can form conjugates with anticancer drugs, their complexes were biophysically characterized using zeta potential and zeta size methods. Next, to confirm the existence of a synergetic effect of dendrimers and drugs, in vitro studies were performed.

The Novel Synthetic Antibiotic BDTL049 Based on a Dendritic System Induces Lipid Domain Formation while Escaping the Cell Envelope Stress Resistance Determinants.

The threat of antimicrobial-resistant bacteria is ever increasing and over the past-decades development of novel therapeutic counter measurements have virtually come to a halt. This circumstance calls for interdisciplinary approaches to design, evaluate and validate the mode of action of novel antibacterial compounds. Hereby, carbosilane dendritic systems that exhibit antimicrobial properties have the potential to serve as synthetic and rationally designed molecules for therapeutic use.

Direct and Reverse Pluronic Micelles: Design and Characterization of Promising Drug Delivery Nanosystems.

Pluronics are a family of amphiphilic block copolymers broadly explored in the pharmaceutical field. Under certain conditions, Pluronics self-assemble in different structures including nanosized direct and reverse micelles. This review provides an overview about the main parameters affecting the micellization process of Pluronics, such as polymer length, fragments distribution within the chain, solvents, additives and loading of cargo.

Carbosilane dendritic nanostructures, highly versatile platforms for pharmaceutical applications.

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.

Synthesis and mechanism-of-action of a novel synthetic antibiotic based on a dendritic system with bow-tie topology.

Over the course of the last decades, the continuous exposure of bacteria to antibiotics-at least in parts due to misprescription, misuse, and misdosing-has led to the widespread development of antimicrobial resistances. This development poses a threat to the available medication in losing their effectiveness in treating bacterial infections. On the drug development side, only minor advances have been made to bring forward novel therapeutics.

Interaction of Cationic Carbosilane Dendrimers and Their siRNA Complexes with MCF-7 Cells Cultured in 3D Spheroids.

Cationic dendrimers are effective carriers for the delivery of siRNA into cells; they can penetrate cell membranes and protect nucleic acids against RNase degradation. Two types of dendrimers (CBD-1 and CBD-2) and their complexes with pro-apoptotic siRNA (Mcl-1 and Bcl-2) were tested on MCF-7 cells cultured as spheroids. Cytotoxicity of dendrimers and dendriplexes was measured using the live-dead test and Annexin V-FITC Apoptosis Detection Kit (flow cytometry).

Dendrimers and Dendritic Materials against Infectious Diseases.

The COVID-19 pandemic showed more deeply the need of our society to provide new therapeutic strategies to fight infectious diseases, not only against currently known illnesses, where common antibiotics and drugs appear to be not fully effective, but also against new infectious threats that may arise [...

Magnetic nanoparticles coated with carboxylate-terminated carbosilane dendrons as a reusable and green approach to extract/purify proteins.

Extraction/purification of proteins, at both analytical and industrial levels, is a limiting step that usually requires the use of organic solvents and involves tedious work and a high cost. This work proposes a more sustainable alternative based on the use of magnetic nanoparticles (MNPs) coated with carboxylate-terminated carbosilane dendrons. MNPs coated with first- and second-generation carbosilane dendrons and bare MNPs were employed for the extraction of proteins with different molecular weights and charges.

Prospects of Cationic Carbosilane Dendronized Gold Nanoparticles as Non-viral Vectors for Delivery of Anticancer siRNAs siBCL-xL and siMCL-1.

Cancer is one of the most important problems of modern medicine. At the present time, gene therapy has been developed against cancer, which includes the delivery of anticancer small interfering RNAs (siRNAs) directed at cancer proteins. The prospect of creating drugs based on RNA interference implies the use of delivery systems.

Cationic Carbosilane Dendrimers Prevent Abnormal α-Synuclein Accumulation in Parkinson's Disease Patient-Specific Dopamine Neurons.

Accumulation of misfolded α-synuclein (α-syn) is a hallmark of Parkinson's disease (PD) thought to play important roles in the pathophysiology of the disease. Dendritic systems, able to modulate the folding of proteins, have emerged as promising new therapeutic strategies for PD treatment. Dendrimers have been shown to be effective at inhibiting α-syn aggregation in cell-free systems and in cell lines.