Supraamphiphilic Systems Based on Metallosurfactant and Calix[4]resorcinol: Self-Assembly and Drug Delivery Potential

Abstract

Metallic amphiphiles are used as building blocks in the construction of nanoscale superstructures, where the hydrophobic effects induce the self-assembly of the nanoparticles of interest. However, the influence of synergizing multiple chemical interactions on an effective design of these structures mostly remains an open question. In this regard, supraamphiphilic systems based on flexible surfactant molecules and rigid macrocycles are being actively developed, but there are few works on the interaction between metallosurfactants and macrocycles. In the present work, the self-assembly and biological properties of a metallosurfactant with calixarene were studied for the first time. The metallosurfactant, a complex between lanthanum nitrate and two 4-aza-1-hexadecylazoniabicyclo[2.2.2]­octane bromide units, and calix[4]­resorcinol containing sulfonate groups on the upper rim were used to form a novel supraamphiphilic composition. The system formed was studied using a variety of physicochemical methods, including spectrophotometry, NMR, XRF, and dynamic and electrophoretic light scattering. It was found that the most optimal tetraanionic calix[4]­resorcinol to dicationic metallosurfactant molar ratio, leading to mixed aggregation upon ion pair complexation, is 2:3. The mixed aggregates formed in the pentamolar concentration range were able to encapsulate hydrophilic substrates, including the anticancer drug cisplatin, the pure form of which is more cytotoxic toward healthy cells than toward diseased cells. Interestingly, the drug loaded into the macrocycle–metallosurfactant particles was less cytotoxic to a healthy Chang liver cell line and more cytotoxic to tumor M-HeLa cells. This selectivity depends on the amount of cisplatin added. The more drug is added to the macrocycle–metallosurfactant composition, the greater the biological activity against cancer cells. Taking into account that the appearance of resistance of cancer cells to drugs, especially to cisplatin, is one of the most important problems in treatment, the results of this work envisage the potential application of a mixed macrocycle–metallosurfactant system for the design of therapeutic cisplatin compositions.

Supramolecular Self-Assembly of Porphyrin and Metallosurfactant as a Drug Nanocontainer Design

“…Since titration of 0.0025 mM TSPP-0.005 mM LaSurf complex with cisplatin revealed the first inflection at the amount of drug equimolar to the amount of the macrocycle, the cytotoxic effect on Chang liver and cancer M-HeLa cell lines at various concentrations of LaSurf were first studied. As can be seen from the Table 2, the presence of cisplatin in the equimolar complex leads to a sharp appearance of the cytotoxic effect, and taking into account the literature data of cytotoxicity for pure cisplatin in water [49], we can say the same about the manifestation of the cytotoxic effect of the triple complex. An increase in the proportion of LaSurf in this ternary complex insignificantly changes the cytotoxicity to both cell lines.…”

“…Lanthanum compounds show high antitumor activity [45][46][47] and are able to regulate the antitumor resistance of the organism [48]. The choice of a lanthanum-containing amphiphile is due to its ability to form joint aggregates with an oppositely charged 3D macrocycle, which can act as a medicinal nanocontainer of cisplatin with improved selectivity towards diseased cells [49]. To the best of our knowledge, there are no data in the literature concerning the complexation of porphyrin with metallosurfactant in the solution.…”

Self-Assembling Systems Based on Pillar[5]arenes and Surfactants for Encapsulation of Diagnostic Dye DAPI

“…As a result, 1:1 host–guest complexes are formed [ 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 ]. In addition, the ability of water-soluble macrocycles, by analogy with non-macrocyclic surfactants, to form various types of associates such as liposomes [ 36 , 37 , 38 ], micelles [ 39 , 40 , 41 ], and liquid crystals [ 42 , 43 ], etc., is well known. It attracts great attention due to their potential application in various fields and especially in biomedicine as nanocontainers for medicinal and imaging agents [ 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 ].…”

Biological properties and conformational studies of amphiphilic Pd(II) and Ni(II) complexes bearing functionalized aroylaminocarbo-N-thioylpyrrolinate units

“…In this line, metal complexes incorporating an amphiphilic character (also called metallosurfactants) exhibit very interesting properties, but their biological and medicinal applications have not been fully developed yet [1,2]. One of the most promising areas of interest in medicine is oncology [3][4][5] and infectious diseases [6][7][8] (or both) [9]. The modulation of the hydrophobicity domain, the influence of the strength of the ligand and the metal cation sphere (together with small molecules coordinated in its outer sphere) are crucial points to study the structure-activity relationship (SAR) onto a fixed biological target [10][11][12].…”