Interaction of bovine serum albumin with cationic imidazolium-containing amphiphiles bearing urethane fragment: Effect of hydrophobic tail length

© 2020 Complexation ability of homologous series of amphiphiles bearing imidazolium and urethane moieties (IAC-n, n = 14, 16, 18) toward bovine serum albumin (BSA) has been investigated by various physico-chemical methods (tensiometry, fluorescence spectroscopy, spectrophotometry, dynamic and electrophoretic light scattering, circular dichroism, and transmission electron microscopy). It has been revealed, that aggregation thresholds of systems based on IAC-n could be 5–8-fold reduced by BSA addition. Fluorescent analysis allows to estimate that binding of components is favorably mediated by tryptophan amino acid residues and is driven by different forces depending on the length of amphiphile hydrophobic tail. In particular, dominate contribution of Van der Waals interactions to the complexation has been shown in the case of IAC-14 and IAC-16, while hydrophobic interactions prevailed for IAC-18. It has been demonstrated that amphiphile addition causes reversible unfolding of protein macromolecules in all cases. Spectrophotometry assay exhibits that amphiphile/BSA complexes have more significant solubilization capacity toward hydrophobic guest in comparison with individual IAC-n systems

Polymer–colloid complexes based on cationic imidazolium amphiphile, polyacrylic acid and dna decamer

The solution behavior and physicochemical characteristics of polymer–colloid complexes based on cationic imidazolium amphiphile with a dodecyl tail (IA-12) and polyacrylic acid (PAA) or DNA decamer (oligonucleotide) were evaluated using tensiometry, conductometry, dynamic and electrophoretic light scattering and fluorescent spectroscopy and microscopy. It has been established that PAA addition to the surfactant system resulted in a ca. 200-fold decrease in the aggregation threshold of IA-12, with the hydrodynamic diameter of complexes ranging within 100–150 nm. Electrostatic forces are assumed to be the main driving force in the formation of IA-12/PAA complexes. Factors influencing the efficacy of the complexation of IA-12 with oligonucleotide were determined. The nonconventional mode of binding with the involvement of hydrophobic interactions and the intercalation mechanism is probably responsible for the IA-12/oligonucleotide complexation, and a minor contribution of electrostatic forces occurred. The latter was supported by zeta potential measurements and the gel electrophoresis technique, which demonstrated the low degree of charge neutralization of the complexes. Importantly, cellular uptake of the IA-12/oligonucleotide complex was confirmed by fluorescence microscopy and flow cytometry data on the example of M-HeLa cells. While single IA-12 samples exhibit roughly similar cytotoxicity, IA-12–oligonucleotide complexes show a selective effect toward M-HeLa cells (IC50 1.1 µM) compared to Chang liver cells (IC50 23.1 µM)

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