Introduction of isothiuronium surfactant series: Synthesis, structure-dependent aggregation overview and biological activity

© 2020 Elsevier B.V. For a homologous series of isothiuronium surfactants (S-alkylisothiuronium bromides, CnSU, where n = 10, 12, 14, 16, 18), a synthesis procedure is described and aggregation properties are comprehensively characterized by a variety of techniques. Krafft temperature and critical micelle concentration (cmc) are obtained by methods of conductometry, tensiometry, spectrophotometry, fluorimetry. Using dynamic light scattering and NMR diffusometry, aggregate sizes in aqueous solutions were determined. The aggregation numbers of CnSU systems were estimated by alternative methods. An increase in the length of the alkyl tail from 10 to 16 carbon atoms leads to a decrease in cmc from 16 to 0.5 mM with a decrease in aggregation numbers. S-alkylisothiuronium bromides exhibit solubilization capacity toward a hydrophobic dye Orange OT which is 2–3 times higher than that of alkyltrimethylammonium analogues. Improved solubilization characteristics along with antimicrobial properties manifested at the concentrations of low hemolytic activity allow us to recommend these amphiphiles for the fabrication of soft nanocontainers for hydrophobic guests showing their own biological functionality

Mitochondria-targeted mesoporous silica nanoparticles noncovalently modified with triphenylphosphonium cation: Physicochemical characteristics, cytotoxicity and intracellular uptake

Novel nanocomposite system based on mesoporous silica nanoparticles (MSNs) noncovalently modified with hexadecyltriphenylphosphonium bromide (HTPPB) has been prepared, thoroughly characterized and used for encapsulation of model cargo Rhodamine B (RhB). The high encapsulation efficacy of this dye by HTPPB-modified mesoporous particles was demonstrated by spectrophotometry and thermography techniques. The bioavailability of MSN@HTPPB was testified. Cytotoxicity assay revealed that a marked suppression of M−HeLa cancer cells (epithelioid carcinoma of the cervix) occurs at concentration of 0.06 μg/mL, while the higher viability of Chang liver normal cell line was preserved in the concentration range of 0.98–0.06 μg/mL. Hemolysis assay demonstrated that only 2% of red blood cells are destructed at ~ 30 μg/mL concentration. This allows us to select the most harmless compositions based on MSN@HTPPB with minimal side effects toward normal cells and recommend them for the development of antitumor formulations. Fluorescence microscopy technique testified satisfactory penetration of HTPPB-modified carriers into M−HeLa cells. Importantly, modification of the MSN with HTPPB is shown to promote efficient delivery to mitochondria. To the best of our knowledge, it is one of the first successful examples of noncovalent surface modification of the MSNs with lipophilic phosphonium cation that improves targeted delivery of loads to mitochondria