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.

Structural, biocomplexation and gene delivery properties of hydroxyethylated gemini surfactants with varied spacer length.

Gemini surfactants with hexadecyl tails and hydroxyethylated head groups bridged with tetramethylene (G4), hexamethylene (G6) and dodecamethylene (G12) spacers were shown to self-assemble at the lower critical micelle concentration compared to their conventional m-s-m analogs. The lipoplex formation and the plasmid DNA transfer into different kinds of host cells were studied. In the case of eukaryotic cells, high transfection efficacy has been demonstrated for DNA-gemini complexes, which increased as follows: G6G4>G12 has been obtained in the case of transformation of bacterial cells with plasmid DNA-gemini complexes, mediated by electroporation technique. Solely G6 shows transformation efficacy exceeding the control result (uncomplexed DNA), while the inhibitory effect occurs for G4 and G12. Analysis of physico-chemical features of single surfactants and lipoplexes shows that compaction and condensation effects change as follows: G6

Self-assembling systems based on amphiphilic alkyltriphenylphosphonium bromides: elucidation of the role of head group.

A systematic study of the aggregation behavior of alkyltriphenylphosphonium bromides (TPPB-n; n=8, 10, 12, 14, 16, 18; here n is the number of carbon atoms in alkyl groups) in aqueous solutions has been carried out and compared with trimethyl ammonium bromides (TMAB-n). Critical micelle concentrations (cmcs) of TPPB-n and TMAB-n decrease with the number of carbon atoms with the slope parameter of ca.0.3. The low cmcs and effective solubilization power toward Orange OT indicate high micellization capacity of phosphonium surfactants. The low counterion binding parameter ß is revealed for TPPB-10 and TPPB-12, while high counterion binding of ≥80% is observed for high TPPB-n homologs. Values of the surface potential ψ calculated on the basis of pK(a) shifts of p-nitrophenols is similar for both series and monotonously increase with alkyl chain length. Several points indicate non-monotonic changes within TPPB-n series. There are peculiarities of the tensiometry and solubilization plots for high homologs and above mentioned increases in counterion binding on transiting from low to high molecular weight surfactants. Differences in aggregation behavior between TPPB and TMAB series and between low and high homologs can be due to the specific structural character of the TPP(+) cation, which is supported by X-ray data.

Nanoreactors based on amphiphilic uracilophanes: self-organization and reactivity study.

New amphiphilic pyrimidinic macrocycles (APMs) with two (APM-1) and three (APM-2) decyl tails have been synthesized by quaternization of the bridged N. Complex examination of the APM-based systems with the help of tensiometry, conductometry, dynamic light scattering, and UV and NMR spectroscopy provides evidence for their aggregation. Calculations based on surface tension isotherms and on packing parameter considerations make it possible to assume a lamellar packing of macrocycles when aggregating. Marked differences in the aggregation behavior of APM-1 and APM-2 have been found. The additives of polyethylenimine (PEI) exert little influence on the critical micelle concentration (cmc) of APM-1, while in the APM-2/PEI systems there occurs a pronounced decrease in the cmc and also a ca. 2-fold decrease in the surface area per molecule. The APM-based assemblies are explored as nanoreactors for the hydrolysis of O-alkyl O-p-nitrophenyl (chloromethyl)phosphonates (alkyl = ethyl, hexyl). The kinetic study reveals a minor rate effect of the APM-1-based systems. In the APM-2-based systems an acceleration of the hydrolysis of both phosphonates occurs as compared to the uncatalyzed process. Within the APM-2 --> APM-2/PEI --> APM-2/PEI/La(III) series, due to the cooperative contributions of the supramolecular, polymer, and homogeneous catalysis, an increase in the catalytic effect is observed from 30 times to 3 orders of magnitude as compared to that of the basic hydrolysis of the substrates.

Nanosized reactors based on polyethyleneimines: from microheterogeneous systems to immobilized catalysts.

Effective nanoreactors based on polyethyleneimines (PEIs) for the hydrolytic cleavage of O-alkyl O-p-nitrophenyl chloromethylphosphonates (alkyl = ethyl, hexyl) and di(p-nitrophenyl)phosphate were developed in conformity with the idea of modeling the polyfunctional catalytic mechanism of enzymes. A step-by-step modification of the single PEI solution by additives with their own catalytic activities (sodium dodecyl sulfate and lanthanum salt) gave rise to a marked improvement in the reaction efficiency. A 104-106-fold acceleration of the reaction compared to the aqueous basic hydrolysis of the substrates was achieved in the sodium dodecyl sulfate-polyethyleneimine-La(III) ternary system. This system can be considered to be metallomicelles immobilized on a hydrophilic polymer matrix. When the PEI immobilized on silica gel was used as a catalyst, the full completion of the reaction was achieved for 100 min under mild conditions, while the half-life of the reaction in a comparable homogeneous regime exceeds 100 h.