Amphiphilic Structure Research Articles

Monitoring Cell Plasma Membrane Polarity by a NIR Fluorescence Probe with Unexpected Cell Plasma Membrane-Targeting Ability.

The cell plasma membrane, the natural barrier of a cell, plays critical roles in a mass of cell physiological and pathological processes. Therefore, revealing and monitoring the local status of the cell plasma membrane are of great significance. Herein, using a near-infrared (NIR) fluorescence probe BTCy, microenvironmental polarity in the cell plasma membrane was in situ monitored. BTCy showed sensitive and selective fluorescence decrease response at 706 nm with the increase of polarity as its polarity-responsive D-π-A structure. Most importantly, BTCy showed unexpected cell plasma membrane-targeting ability, probably due to its amphiphilic structure. With BTCy, the distinguishing imaging of cancer and normal cells was done, in which cancer cells exhibited significantly stronger signals due to their lower cell plasma membrane polarity. In addition, with the imaging of BTCy, the ferroptosis process was revealed with no significant cell plasma membrane polarity variation for the first time. Furthermore, BTCy was employed for in vivo imaging of tumor tissue in the 4T1-tumor-bearing mice. The polarity-responsive and cell plasma membrane-targeting properties of BTCy make it a useful tool for monitoring cell plasma membrane polarity variation, providing an efficient and simple method for tumor diagnosis.

Inhibiting ice recrystallization by amyloid protein fibrils

Ice recrystallization is harmful to the quality of frozen foods and the cryopreservation of cells and biological tissues, requiring biocompatible materials with ice recrystallization inhibition (IRI) activity. Emerging studies have associated IRI activity with amphiphilic structures. We propose amphiphilic amyloid protein fibrils (APFs) may be IRI-active. APFs were prepared from whey protein isolate (WPI) in water (W-APFs) and in trifluoroethanol (TFE-APFs). W-APFs and TFE-APFs were more IRI-active than WPI over a concentration range of 2.5–10.0 mg/mL. Both APFs showed stronger IRI activity at pH 3.0 than at pH 5.0, 7.0, and 10.0, which was ascribed to the effect of water dispersibility and fibril length. The reduced IRI activity of the two APFs with increasing NaCl content was caused by fibril aggregation. Ice binding by APFs was absent or very weak. Ordered water was observed for the two APFs, which might be essential for IRI activity. Our findings may lead to the use of APFs as novel ice recrystallization inhibitors.

Molecular Diversity of Linear Peptides Revealed by Transcriptomic Analysis of the Venom Gland of the Spider Lycosa poonaensis.

Spider venom is a complex mixture of bioactive components. Previously, we identified two linear peptides in Lycosa poonaensis venom using mass spectrometric analysis and predicted the presence of more linear peptides therein. In this study, a transcriptomic analysis of the L. poonaensis venom gland was conducted to identify other undetermined linear peptides in the venom. The results identified 87 contigs encoding peptides and proteins in the venom that were similar to those in other spider venoms. The number of contigs identified as neurotoxins was the highest, and 15 contigs encoding 17 linear peptide sequences were identified. Seven peptides that were representative of each family were chemically synthesized, and their biological activities were evaluated. All peptides showed significant antibacterial activity against Gram-positive and Gram-negative bacteria, although their selectivity for bacterial species differed. All peptides also exhibited paralytic activity against crickets, but none showed hemolytic activity. The secondary structure analysis based on the circular dichroism spectroscopy showed that all these peptides adopt an amphiphilic α-helical structure. Their activities appear to depend on the net charge, the arrangement of basic and acidic residues, and the hydrophobicity of the peptides.

Design of Nanostructured Hybrid Electrodes Based on a Liquid Crystalline Zn(II) Coordination Complex-Carbon Nanotubes Composition for the Specific Electrochemical Sensing of Uric Acid

A metallomesogen based on an Zn(II) coordination complex was employed as precursor to obtain a complex matrix nanoplatform for the fabrication of a high-performance electrochemical hybrid sensor. Three representative paste electrodes, which differ by the weight ratio between Zn(II) metallomesogen and carbon nanotubes (CNT), i.e., PE_01, PE_02 and PE_03, were obtained by mixing the materials in different amounts. The composition with the largest amount of CNT with respect to Zn complex, i.e., PE_03, gives the best electrochemical signal for uric acid detection by cyclic voltammetry in an alkaline medium. The amphiphilic structure of the Zn(II) coordination complex likely induces a regular separation between the metal centers favoring the redox system through their reduction, followed by stripping, and is characterized by enhanced electrocatalytic activity towards uric acid oxidation. The comparative detection of uric acid between the PE_03 paste electrode and the commercial zinc electrode demonstrated the superiority of the former, and its great potential for the development of advanced electrochemical detection of uric acid. Advanced electrochemical techniques, such as differential-pulsed voltammetry (DPV) and square-wave voltammetry (SWV), allowed for the highly sensitive detection of uric acid in aqueous alkaline solutions. In addition, a good and fast amperometric signal for uric acid detection was achieved by multiple-pulsed amperometry, which was validated by urine analysis.

A hydrophilic-lipophilic triazine based hyper-crosslinked polymer for efficient enrichment of nitrobenzene compounds

Sensitive, accurate, and simultaneous determination of nitrobenzene compounds (NBs) in environmental water samples is of great significance due to their high risk to human health. In this work, a new triazine-based hyper-crosslinked polymer named CC-Py was constructed via the Friedel-Crafts reaction between cyanuric chloride (CC), pyridine (Py) and 1,2-dichloroethane. Due to its excellent stability, high surface area and hydrophilic-lipophilic (amphiphilic) structure, the CC-Py exhibited a high affinity toward the NBs (nitrobenzene, 2-nitrotoluene, 2,6-dimethylnitrobenzene, 3-nitrotoluene, 4-nitrotoluene, 3-nitrochlorobenzene, 4-nitrochlorobenzene, 2-nitrochlorobenzene, 2,4-dimethylnitrobenzene, 3-nitrobromobenzene, 4-nitrobromobenzene and 4-nitroiodobenzene). Then, a CC-Py based solid-phase microextraction coupled with gas chromatography-flame ionization detection was developed to detect the twelve NBs in real water samples. The results showed that the method had low limits of detection (0.20–0.50 μg L−1), good reproducibility (relative standard deviations (RSDs) < 8.6%) and high enrichment factors (967–1590). The recoveries for the NBs in six different types of water samples were between 90% and 111% with the RSDs less than 7.5%. This work provides a facile and sensitive method for the determination of trace level of NBs in real water samples.

The Unexpected Role of Cations in the Self-Assembly of Positively Charged Amphiphiles at Liquid/Liquid Interfaces.

Conventional wisdom suggests that cations play a minimal role in the assembly of cationic amphiphiles. Here, we show that at liquid/liquid (L/L) interfaces, specific cation effects can modulate the assemblies of hydrophobic tails in an oil phase despite being attached to cationic headgroups in the aqueous phase. We used oligo-dimethylsiloxane (ODMS) methyl imidazolium amphiphiles to identify these specific interactions at hexadecane/aqueous interfaces. Small cations, such as Li+, bind to the O atoms in the ODMS tail and pin it to the interface, thereby imposing a kinked conformation─as evidenced by vibrational sum frequency generation spectroscopy and molecular dynamics simulations. While larger Cs+ ions more readily partition to the interface, they do not form analogous complexes. Our data not only point to ways for controlling amphiphile structure at L/L interfaces but also suggest a means for the separation of Li+, or related applications, in soft-matter electronics.

Heterogeneous Structural Disturbance of Cell Membrane by Peptides with Modulated Hydrophobic Properties.

Extensive effort has been devoted to developing new clinical therapies based on membrane-active peptides (MAPs). Previous models on the membrane action mechanisms of these peptides mostly focused on the MAP-membrane interactions in a local region, while the influence of the spatial heterogeneity of the MAP distribution on the membrane was much ignored. Herein, three types of natural peptide variants, AS4-1, AS4-5, and AS4-9, with similar amphiphilic α-helical structures but distinct hydrophobic degrees (AS4-1 &lt; AS4-5 &lt; AS4-9) and net charges (+9 vs. +7 vs. +5), were used to interact with a mixed phosphatidylcholine (PC) and phosphatidylglycerol (PG) membrane. A combination of giant unilamellar vesicle (GUV) leakage assays, atomic force microscopy (AFM) characterizations, and molecular dynamics (MD) simulations demonstrated the coexistence of multiple action mechanisms of peptides on a membrane, probably due to the spatially heterogeneous distribution of peptides on the membrane surface. Specifically, the most hydrophobic peptide (i.e., AS4-9) had the strongest membrane binding, perturbation, and permeabilization effects, leading to the formation of large peptide-lipid aggregates (10 ± 5 nm in height and 150 ± 50 nm in size), as well as continuous fragments and ridges on the supported membrane surface. The AS4-5 peptides, with a half-hydrophilic and half-hydrophobic structure, induced membrane lysis in addition to reconstruction. The most hydrophilic peptide AS4-1 only exhibited unstable binding on the supported membrane surface. These results demonstrate the heterogeneous structural disturbance of model cell membranes by amphiphilic α-helical peptides, which could be significantly strengthened by increasing the degree of hydrophobicity and/or local number density of peptides. This work provides support for the modulation of the membrane activity of MAPs by adjusting their hydrophobicity and local concentration.

Interaction of Direct Blue 86 with cationic surfactant micelles: spectroscopic, conductometric and thermodynamic aspects

Abstract Due to the amphiphilic structure of surfactants, aqueous surfactant solutions can behave like very good solvents and dissolve both polar and non-polar solutes. This study reports on the solubilisation of a direct dye (Direct Blue 86) in a micellar medium using the cationic surfactant cetyltrimethylammonium bromide (CTAB). Solubilisation of dyes is important for their subsequent removal from aqueous media. UV spectroscopy and conductometry, among others, were used to quantitatively evaluate this process. The extent of solubilisation, the interaction between the molecules and the stability of the processes were checked using the partition coefficient (K x), the binding constant (K b) and the corresponding thermodynamic parameters. From the results, it could be concluded that the solubilisation of Direct Blue 86 is a spontaneous process supported by an increase in entropy. It was also found that the micellar medium CTAB is efficient for solubilisation and binding of the dye and can be used economically.

Cellulose-incorporated imprinted materials with amphiphilic crosslinking structure for selective adsorption of bisphenol A

The development of cost-effective and easy-operate adsorbents with tunable adsorption performance is of great importance while remains a big challenge. Herein, cellulose-incorporated imprinted material (CMC-MIPs) with solvent-regulated adsorption property was designed and synthesized using the functionalized cellulose (CMC-MA) as main cross-linker with the assistance of co-crosslinking agent divinyl benzene for selective adsorption of bisphenol A (BPA). Styrene was used as functional monomer to interact with BPA through π-π stacking interaction. And CMC-MA could interact with BPA by multi-hydrogen bonding to strengthen the binding interaction. Adsorption experiments demonstrated that the obtained CMC-MIPs exhibited high adsorption capacity (16.23 mg/g) and excellent selectivity (imprinting factor: 16.07) towards BPA. And CMC-MIPs can easily adsorb BPA in aqueous solution, while release most of the adsorbed BPA in organic media (i.e., methanol or ethanol), indicating excellent solvent-regulated adsorption/release property. The developed CMC-MIPs were successfully employed for selective adsorption of BPA from milk samples with satisfactory recoveries. The proposed construction strategy will offer new sights on the fabricating the cellulose-introduced imprinted materials with selective adsorption capability for target analytes.

Lidosomes: Innovative Vesicular Systems Prepared from Lidocaine Surfadrug.

Lidocaine is a local anaesthetic drug with an amphiphilic structure able to self-associate, under certain conditions, in molecular aggregates playing the role of both carrier and drug. The aim of this study was to determine the optimal conditions for obtaining vesicular carriers, called lidosomes. The new formulations were obtained using both lidocaine and lidocaine hydrochloride and different hydration medias (distilled water, acid, and basic aqueous solution). Lidosomes formulations were characterized in terms of size, ζ-potential, drug retained, stability formulation, and ex vivo permeation profile. Moreover, lidosomes were incorporated in two different gel structures: one based on carboxymethylcellulose and one based on pluronic F-127 to achieve suitable properties for a topical application. Results obtained showed that lidocaine showed a better performance to aggregate in vesicular carriers in respect to hydrochloride form. Consequently, only formulations comprised of lidocaine were studied in terms of skin permeation performance and as carriers of another model drug, capsaicin, for a potential combined therapy. Lidocaine, when in form of vesicular aggregates, acted as percutaneous permeation enhancer showing better permeation profiles with respect to drug solutions. Moreover, lidosomes created a significant drug depot into the skin from which the drug was available for a prolonged time, a suitable feature for a successful local therapy.

Experimental evaluation of non-ionic mixed surfactant formulations at high-temperature and high-salinity conditions

Non-ionic alkyl polyglucoside (APG) surfactants have been considered as eco-friendly, nontoxic and biodegradable surfactants. This study investigated the feasibility and advantages of new formulations for mixed surfactants consisting of a commerical APG product and one of the following alkyl amines (AAs) – dodecylamine (C12A), tetradecylamine (C14A), hexadecylamine (C16A), and octadecylamine (C18A) for improved oil production applications in carbonate reservoirs under high-temperature and high-salinity (HTHS) conditions. The physicochemical properties including compatibility, surface tension, interfacial tension (IFT), static adsorption, wettability alteration of the solutions comprising APG and various AA under HTHS conditions were evaluated. The self-assemble behavior of molecules between APG and C12A was characterized based on the Scanning Electron Microscopy (SEM) analysis. The formulations with an ultra-low IFT were introduced and the mechanisms resulting in such ultra-low IFT were further studied and discussed. The yielded APG/AA formulation was injected as the chemical flooding agent into a micromodel to investigate the efficiency of oil displacement. Commercial APG products exhibited excellent compatibility with the simulated injection water at reservoir temperature. After mixed with AA, the APG solution became hazy or phase separated above a critical concentration (Ccrit) of AA. Ccrit was found to decrease with an increase of the hydrocarbon chain, suggesting that more APG surfactants are required to solubilize the AA with longer alkyl hydrocarbon chain. In the presence of AA, the critical micelle concentration (CMC) of APG surfactant significantly reduced due to the formation of a compact micellar structure. APG yielded a low IFT at 90 °C and a concentration of 2 g/L in the order of 10−2 mN/m, while an ultra-low IFT in the order of 10−3 mN/m was obtained upon addition of a small amount (0.3–0.5 g/L) of C12A. SEM images and proposed IFT reduction mechanisms indicated that APG and C12A synergistically generated a more compact structure via hydrophobic interaction between the hydrophobic moieties and hydrogen bonding between the hydrophilic parts of the chemicals comparing the aggregated structure formed by APG alone, such effect could eventually lead to a decrease in IFT between oil and water. The amounts of chemical adsorption and contact angle of an oil droplet on carbonate cores were not affected upon addition of AA. The micromodel test showed that the produced oil by injection of the designed APG/AA formulations was further enhanced after water flooding. Among the formulations, APG/C12A flooding resulted in a highest effectiveness on oil displacement with a cumulative oil production of 78.7% at the end of injections. To sum up, new APG/AA-based formulations were designed with an ultra-low IFT resulting from a much compact amphiphilic structure along oil-water interface. This study shows a great potential of APG surfactant and the related formulations in improving oil production for HTHS carbonate reservoirs.

Quaternary ammonium compounds in hypersensitivity reactions.

Quaternary ammonium compounds (QAC) are commonly used disinfectants, antiseptics, preservatives, and detergents due to their antibacterial property and represent the first used biocides before phenolic or nitrogen products. Their common structure consists of one or more quaternary ammonium bound with four lateral substituents. Their amphiphilic structure allows them to intercalate into microorganism surfaces which induces an unstable and porous membrane that explains their antimicrobial activity towards bacteria, fungi, and viruses. QAC are thus found in many areas, such as household products, medicines, hygiene products, cosmetics, agriculture, or industrial products but are also used in medical practice as disinfectants and antiseptics and in health care facilities where they are used for cleaning floors and walls. QAC exposure has already been involved in occupational asthma in healthcare workers or professional cleaners by many authors. They also have been suggested to play a role in contact dermatitis (CD) and urticaria in workers using cosmetics such as hairdressers or healthcare workers, inciting reglementary agencies to make recommendations regarding those products. However, distinguishing the irritant or sensitizing properties of chemicals is complex and as a result, the sensitizing property of QAC is still controverted. Moreover, the precise mechanisms underlying the possible sensitization effect are still under investigation, and to date, only a few studies have documented an immunological mechanism. Besides, QAC have been suggested to be responsible for neuromuscular blocking agents (NMBA) sensitization by cross-reactivity. This hypothesis is supported by a higher prevalence of quaternary ammonium (QA)-specific IgE in the professionally exposed populations, such as hairdressers, cleaners, or healthcare workers, suggesting that the sensitization happens with structurally similar compounds present in the environment. This review summarizes the newest knowledge about QAC and their role in hypersensitivities. After describing the different QAC, their structure and use, the most relevant studies about the effects of QAC on the immune system will be reviewed and discussed.

Computer-Aided Design of Lasso-like Self-Assembling Anticancer Peptides with Multiple Functions for Targeted Self-Delivery and Cancer Treatments.

Anticancer peptides are promising drug candidates for cancer treatment, but the short circulation time and low delivery efficiency limit their clinical applications. Herein, we designed several lasso-like self-assembling anticancer peptides (LASAPs) integrated with multiple functions by a computer-aided approach. Among these LASAPs, LASAP1 (CRGDKGPDCGKAFRRFLGALFKALSHLL, 1-9 disulfide bond) was determined to be superior to the others because it can self-assemble into homogeneous nanoparticles and exhibits improved stability in serum. Thus, LASAP1 was chosen for proving the design idea. LASAP1 can self-assemble into nanoparticles displaying iRGD on the surface because of its amphiphilic structure and accumulate to the tumor site after injection because of the EPR effect and iRGD targeting to αVβ3 integrin. The nanoparticles could disassemble in the acidic microenvironment of the solid tumor, and cleaved by the overexpressed hK2, which was secreted by prostate tumor cells, to release the effector peptide PTP-7b (FLGALFKALSHLL), which was further activated by the acidic pH. Therefore, LASAP1 could target the orthotopic prostate tumor in the model mice after intraperitoneal injection and specifically inhibit tumor growth, with low systematic toxicity. Combining the multiple targeting functions, LASAP1 represents a promising design of self-delivery of peptide drugs for targeted cancer treatments.

Controllable Construction of Temperature-Sensitive Supramolecular Hydrogel Based on Cellulose and Cyclodextrin.

In temperature sensitive hydrogels, the swelling degree or light transmittance of the gel itself changes with variations in ambient temperature, prompting its wide application in controlled drug release, tissue engineering, and material separation. Considering the amphiphilic structure of β-cyclodextrin (β-CD), a cellulose-based supramolecular hydrogel with superior temperature sensitivity was synthesized based on a combination of cellulose and β-CD as well as the host–guest interaction between β-CD and polypropylene glycol (PPG). In the one-pot tandem reaction process, chemical grafting of β-CD on cellulose and the inclusion complexation of β-CD with PPG were performed simultaneously in a NaOH/urea/water system. The obtained supramolecular hydrogel had a lower critical solution temperature (LCST) of 34 °C. There existed covalent bonding between the cellulose and β-CD, host–guest complexation between the β-CD and PPG, and hydrogen bonding and hydrophobic interactions between the components in the network structure of the supramolecular hydrogel. The combination of various covalent and non-covalent bonds endowed the resulting supramolecular hydrogel with good internal network structure stability and thermal stability, as well as sensitive temperature responsiveness within a certain range—implying its potential as a smart material in the fields of medicine, biology, and textiles. This work is expected to bring new strategies for the fabrication of cellulose-based thermosensitive materials, benefitting the high-value utilization of cellulose.

Structural characterization and emulsifier property of yeast mannoprotein enzymatically prepared with a β-1,6-glucanase

Yeast cell wall mannoprotein with diverse structures and functions are effective emulsifiers due to the amphiphilic structure comprising a protein backbone and mannan chains. In this study, a β-1,6-glucanase-based approach to produce mannoproteins from baker's yeast was established. Batch production of mannoprotein MP112 was realized with 11.1% yield, 90.7% purity, and a mannan to protein ratio of 14.5. The mannan-protein conjugate structure was confirmed by composition analysis, FT-IR and NMR spectrometry, as well as SEM observation, and the assembled mesoporous structure with filamentous fibers was deduced to determine the favorable emulsifying properties from rheological analysis. Application of mannoprotein-based emulsion in the preparation of porcine myofibrillar protein gels showed that MP112 improves the properties of myofibrillar protein composite gels by the formation of a fine-stranded gel network with enhanced protein-polysaccharide-water interactions, which reduce damage to the muscle tissue and increase product quality. This study is expected to broaden the applications of mannoproteins as value-added ingredients.

Selection of competitive adsorption additives to relieve product inhibition of maleic acid hydrogenation in proton exchange membrane flow cell reactor: A molecular dynamics simulation

Adsorption of products on carbon carriers and the sluggish mass transport of products in the catalytic layer lead to product inhibition in proton exchange membrane flow cell reactor (PEMFCR), which seriously decreases hydrogenation performance. Here, via molecular dynamics simulations, an alleviative mechanism of competitive adsorption additives on product inhibition is proposed by choosing biomass derivatives maleic acid (MA) as hydrogenation model compound and ethanol (EtOH) as an additive model. The enhanced solvation and competitive adsorption synergistically promote the outflow of product succinic acid (SA) from the catalytic layer. Strong hydrophobic-hydrophobic interactions between EtOH and SA promote solvation and solubility of SA in the solvent water, and meanwhile the competitive adsorption steric hindrance of EtOH on adsorption interfaces weakens van der Waals interactions between SA and carbon carriers. Accordingly, the main structural characteristics that influence competitive adsorption of additives, such as, amphiphilic structure, polarity, molecular weight, and size of hydrophobic moiety, are exacted for selection of favorable additives. Among the studied water miscible alcohol and ketone additives, isopropanol (iPrOH) is proved to be favorable, which is further verified by the highest increase (64.3%) of hydrogenation conversion of MA in experiments. This work could provide theoretical guidance for selecting high-performance additives, intensifying heterogeneous hydrogenation in PEMFCR.

A Lagrangian particle-based numerical model for surfactant-laden droplets at macroscales

Atmospheric aerosols can consist of inorganic and organic substances, including surfactants at a significant concentration. Importantly, the latter can reduce the surface tension at the liquid–vapor surfaces, where they preferentially adsorb due to their amphiphilic structure. As a result, processes such as droplet coalescence, development of precipitation, and ultimately cloud lifetime may depend on the presence of surfactants in the aerosols. Here, we present a numerical model for cloud droplet formation, which is based on the Lagrangian particle-based microphysics-scheme superdroplet method and takes into account the presence of the surfactant in the droplets. Our results show that surfactant facilitates cloud formation by increasing the number and size of activated droplets, which concentrate at the bottom of the cloud, while the largest droplets are concentrated at the top of the cloud. This indicates a circulation of droplets that involves activation and growth processes from the bottom of the cloud toward the top. Moreover, our conclusions are independent of the particular approach used for modeling the diffusion of Eulerian variables due to the subgrid-scale turbulence. We anticipate that our results will enrich our understanding of the role of surfactants in the behavior of atmospheric aerosols and, importantly, will pave the way for further developments in the numerical modeling of systems with surfactants at macroscopic scales.

Screening of Biosurfactant-producing Bacteria from Symbiotic Microbes with Gastropods in the Persian Gulf

Introduction: Biosurfactants or surface-active compounds with amphiphilic molecular structures, including a hydrophilic and a hydrophobic domain, are produced by microorganisms. These compounds increase the biodegradation of hydrocarbons in the environment due to their ability to emulsify hydrocarbon-water mixtures. This study was conducted to isolate and characterize biosurfactant-producing bacteria from the samples of Gastropods. &#x0D; Materials and Methods: The gastropod samples were collected from oil-contaminated sites in the Persian Gulf, Middle East. Biosurfactant-producing strains were isolated from these samples. The biosurfactant production ability was analyzed using Drop Collapse TEST, oil spreading test, emulsification activity test, and BATH test.&#x0D; Results: In total, 11 biosurfactant-producing strains were isolated. Two isolates with higher growth rates and biosurfactant production ability were selected for further studies. The best isolates were identified as Halomonas sp. isolate BHA16 and Vibrio alginolyticus isolate BHA 17 based on molecular analysis. Gas chromatography analysis of remaining crude oil confirmed that these strains could degrade to 51.44 % and 67.58% of crude oil, respectively.&#x0D; Conclusion: The results of this study indicated the surfactant activity of the bacterial strains isolated from Gastro pods had a good potential for the biodegradation of crude oil and could be used for the cleanup of oil-contaminated marine environments.

Amphiphilic Aminated Derivatives of [60]Fullerene as Potent Inhibitors of Tumor Growth and Metastasis.

Malignant proliferation and metastasis are the hallmarks of cancer cells. Aminated [70]fullerene exhibits notable antineoplastic effects, promoting it a candidate for multi‐targeted cancer drugs. It is an urgent need to reveal the structure–activity relationship for antineoplastic aminated fullerenes. Herein, three amphiphilic derivatives of [60]fullerene with clarified molecular structures are synthesized: TAPC‐4, TAPC‐3, and TCPC‐4. TAPC‐4 inhibits the proliferation of diverse tumor cells via G0/G1 cell cycle arrest, reverses the epithelial–mesenchymal transition, and abrogates the high mobility of tumor cells. TAPC‐4 can be excreted from the organism and achieves an in vivo inhibition index of 75.5% in tumor proliferation and 87.5% in metastatic melanoma with a wide safety margin. Molecular dynamics simulations reveal that the amphiphilic molecular structure and the ending amino groups promote the targeting of TAPC‐4 to heat shock protein Hsp90‐beta, vimentin, and myosin heavy chain 9 (MYH9), probably resulting in the alteration of cyclin D1 translation, vimentin expression, and MYH9 location, respectively. This work initially emphasizes the dominant role of the amphiphilic structure and the terminal amino moieties in the antineoplastic effects of aminated fullerenes, providing fundamental support for their anti‐tumor drug development.

Enhancement of the Bioavailability and Anti-Inflammatory Activity of Glycyrrhetinic Acid via Novel Soluplus®-A Glycyrrhetinic Acid Solid Dispersion.

Glycyrrhetinic acid (GA) is an anti-inflammatory drug with potential for development. However, the poor solubility of GA in water leads to extremely low bioavailability, which limits its clinical applications. Solid dispersions have become some of the most effective strategies for improving the solubility of poorly soluble drugs. Soluplus®, a non-cytotoxic amphiphilic solubilizer, significantly improves the solubility of BCS II drugs and improves the bioavailability of insoluble drugs. l-arginine (L-Arg) can be used as a small molecular weight excipient to assist in improving the solubility of insoluble drugs. In this study, we developed a new formulation for oral administration by reacting GA and L-Arg to form salts by co-solvent evaporation and then adding the polymer-solvent Soluplus® with an amphiphilic chemical structure to prepare a solid dispersion GA-SD. The chemical and physical properties of GA-SD were characterized by DLS, TEM, XRD, FT-IR and TG. The anti-inflammatory activity of GA-SD was verified by LPS stimulation of RAW 267.5 cells simulating a cellular inflammation model, TPA-induced ear edema model in mice, and ethanol-induced gastric ulcer model. The results showed that the amide bond and salt formation of GA-SD greatly improved GA solubility. GA-SD effectively improved the anti-inflammatory effect of free GA in vivo and in vitro, and GA-SD had no significant effect on liver and kidney function, no significant tissue toxicity, and good biosafety. In conclusion, GA-SD with L-Arg and Soluplus® is an effective method to improve the solubility and bioavailability of GA. As a safe and effective solid dispersion, it is a promising anti-inflammatory oral formulation and provides some references for other oral drug candidates with low bioavailability.