Efficient and safe carriers of genetic material are crucial for advancing gene therapy. Three new series of cationic dendritic nanocarriers based on a carbosilane scaffold, differentiated by peripheral modifications: saccharide (CS-glyco), amine (CS-N), and phosphonium dendrimers (CS-P) were designed for binding, protecting, and releasing polyanionic compounds like therapeutic siRNA. Besides introducing synthetic methodology, this study brings a unique direct interstructural comparison of 16 dendritic nanovector's characteristics, addressing a gap in typical research that focuses on uniform structural types. The study evaluates the dendrimer's in vitro cytotoxicity, biophysical properties, and complexation capabilities in comparison with widely used PAMAM dendrimers. CS-glyco and PAMAMs were significantly less toxic to MCF-7 and THP-1 cell lines than were CS-N and CS-P, despite having the same peripheral charge density. Notably, CS-glyco maintained biocompatibility comparable to analogous neutral CS glycodendrimers, underscoring the exceptional capability of sugar coating to reduce toxicity. Dendriplexes formed from these nanocarriers protected siRNA from RNase degradation and facilitated its release in the presence of heparin, highlighting its potential in gene delivery applications. The study provides a background for future in-depth investigations into the introduced dendritic nanocarriers, which show significant potential for advancing drug delivery.

• Publication type
• Journal Article MeSH

Here, we present a modular synthesis as well as physicochemical and biological evaluation of a new series of amphiphilic dendrons carrying triphenylphosphonium groups at their periphery. Within the series, the size and mutual balance of lipophilic and hydrophilic domains are systematically varied, changing the dendron shape from cylindrical to conical. In physiological solution, the dendrons exhibit very low critical micelle concentrations (2.6-4.9 μM) and form stable and uniform micelles 6-12 nm in diameter, depending on dendron shape; the results correlate well with molecular dynamics simulations. The compounds show relatively high cytotoxicity (IC50 1.2-21.0 μM) associated with micelle formation and inversely related to the size of assembled particles. Depending on their shape, the dendrons show promising results in terms of dendriplex formation and antibacterial activity. In addition to simple amphiphilic dendrons, a fluorescently labeled analogue was also prepared and utilized as an additive visualizing the dendron's cellular uptake.

• MeSH
• Anti-Bacterial Agents pharmacology   chemistry   chemical synthesis   MeSH
• Dendrimers * chemistry   chemical synthesis   pharmacology   MeSH
• Hydrophobic and Hydrophilic Interactions MeSH
• Humans MeSH
• Micelles * MeSH
• Organophosphorus Compounds * chemistry   MeSH
• Surface-Active Agents chemistry   chemical synthesis   pharmacology   MeSH
• Silanes chemistry   MeSH
• Molecular Dynamics Simulation MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Anti-Bacterial Agents MeSH
• carbosilane MeSH Browser
• Dendrimers * MeSH
• Micelles * MeSH
• Organophosphorus Compounds * MeSH
• Surface-Active Agents MeSH
• Silanes MeSH

The consideration of human and environmental exposure to dendrimers, including cytotoxicity, acute toxicity, and cell and tissue accumulation, is essential due to their significant potential for various biomedical applications. This study aimed to evaluate the biodistribution and toxicity of a novel methoxyphenyl phosphonium carbosilane dendrimer, a potential mitochondria-targeting vector for cancer therapeutics, in 2D and 3D cancer cell cultures and zebrafish embryos. We assessed its cytotoxicity (via MTT, ATP, and Spheroid growth inhibition assays) and cellular biodistribution. The dendrimer cytotoxicity was higher in cancer cells, likely due to its specific targeting to the mitochondrial compartment. In vivo studies using zebrafish demonstrated dendrimer distribution within the vascular and gastrointestinal systems, indicating a biodistribution profile that may be beneficial for systemic therapeutic delivery strategies. The methoxyphenyl phosphonium carbosilane dendrimer shows promise for applications in cancer cell delivery, but additional studies are required to confirm these findings using alternative labelling methods and more physiologically relevant models. Our results contribute to the growing body of evidence supporting the potential of carbosilane dendrimers as vectors for cancer therapeutics.

• MeSH
• Zebrafish MeSH
• Dendrimers * toxicity   MeSH
• Humans MeSH
• Neoplasms * drug therapy   MeSH
• Cell Culture Techniques, Three Dimensional MeSH
• Tissue Distribution MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• carbosilane MeSH Browser
• Dendrimers * MeSH

Supramolecular structures, such as micelles, liposomes, polymerosomes or dendrimerosomes, are widely studied and used as drug delivery systems. The behavior of amphiphilic building blocks strongly depends on their spatial distribution and shape of polar and nonpolar component. This report is focused on the development of new versatile synthetic protocols for amphiphilic carbosilane dendrons (amp-CS-DDNs) capable of self-assembly to regular micelles and other supramolecular objects. The presented strategy enables the fine modification of amphiphilic structure in several ways and also enables the facile connection of a desired functionality. DLS experiments demonstrated correlations between structural parameters of amp-CS-DDNs and the size of formed nanoparticles. For detailed information about the organization and spatial distribution of amp-CS-DDNs assemblies, computer simulation models were studied by using molecular dynamics in explicit water.

• Keywords
• DLS, amphiphiles, carbosilane, computer modeling, dendrons, micelles, molecular dynamics, zeta potential,
• MeSH
• Anthracenes chemistry   MeSH
• Hydrophobic and Hydrophilic Interactions MeSH
• Micelles MeSH
• Nanoparticles chemistry   MeSH
• Computer Simulation MeSH
• Silanes chemistry   MeSH
• Water chemistry   MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Anthracenes MeSH
• carbosilane MeSH Browser
• dendron MeSH Browser
• Micelles MeSH
• Silanes MeSH
• Water MeSH

A novel approach to inducing anion transport over the dialytic membrane was proposed and successfully tested using the dihydrogen phosphate anion. The anion receptor based on isophthalamide was anchored on a dendritic skeleton, resulting in a macromolecular structure with a limited possibility to cross the dialytic membrane. The dendritic receptor was placed in a compartment separated from a mother anion solution by a membrane. The resulting anion complexation reduced the actual concentration of the anion and induced the anion transfer across the membrane. The anion concentration in mother solution decreased, while it was found to be increased in the compartment with the dendritic receptor. This phenomenon was observed using dendritic receptors with four and eight complexation sites. A detailed analysis of a series of dialytic experiments by 1H NMR spectroscopy enabled an assessment of the complexation behavior of both receptors and an evaluation of the dendritic effect on the anion complexation.

• Publication type
• Journal Article MeSH