Wireless electrical-molecular quantum signalling for cancer cell apoptosis.

Quantum biological tunnelling for electron transfer is involved in controlling essential functions for life such as cellular respiration and homoeostasis. Understanding and controlling the quantum effects in biology has the potential to modulate biological functions. Here we merge wireless nano-electrochemical tools with cancer cells for control over electron transfer to trigger cancer cell death. Gold bipolar nanoelectrodes functionalized with redox-active cytochrome c and a redox mediator zinc porphyrin are developed as electric-field-stimulating bio-actuators, termed bio-nanoantennae. We show that a remote electrical input regulates electron transport between these redox molecules, which results in quantum biological tunnelling for electron transfer to trigger apoptosis in patient-derived cancer cells in a selective manner. Transcriptomics data show that the electric-field-induced bio-nanoantenna targets the cancer cells in a unique manner, representing electrically induced control of molecular signalling. The work shows the potential of quantum-based medical diagnostics and treatments.

Molecular Surface Quantification of Multifunctionalized Gold Nanoparticles Using UV-Visible Absorption Spectroscopy Deconvolution.

Multifunctional gold nanoparticles (AuNPs) are of great interest, owing to their vast potential for use in many areas including sensing, imaging, delivery, and medicine. A key factor in determining the biological activity of multifunctional AuNPs is the quantification of surface conjugated molecules. There has been a lack of accurate methods to determine this for multifunctionalized AuNPs. We address this limitation by using a new method based on the deconvolution and Levenberg-Marquardt algorithm fitting of UV-visible absorption spectrum to calculate the precise concentration and number of cytochrome C (Cyt C) and zinc porphyrin (Zn Porph) bound to each multifunctional AuNP. Dynamic light scattering (DLS) and zeta potential measurements were used to confirm the functionalization of AuNPs with Cyt C and Zn Porph. Transmission electron microscopy (TEM) was used in conjunction with UV-visible absorption spectroscopy and DLS to identify the AuNP size and confirm that no aggregation had taken place after functionalization. Despite the overlapping absorption bands of Cyt C and Zn Porph, this method was able to reveal a precise concentration and number of Cyt C and Zn Porph molecules attached per AuNP. Furthermore, using this method, we were able to identify unconjugated molecules, suggesting the need for further purification of the sample. This guide provides a simple and effective method to quickly quantify molecules bound to AuNPs, giving users valuable information, especially for applications in drug delivery and biosensors.

GC-MS metabolomics profile of methanol extract of Acacia modesta gum and gum-assisted fabrication and characterization of gold nanoparticles through green synthesis approach.

Hereunder, for the first time, we reported phytocompounds in the methanolic extract of Acacia modesta (AM) gum through Gas chromatography-mass spectrometry (GS-MS). Further, the AM gum aqueous solution was used for gold nanoparticles (AuNPs) synthesis through a simple, swift, eco-friendly, and less costly green synthesis approach. A total of 108 phytocompounds (63 with nonpolar, 45 with polar column) were identified in the gum extract, which includes fatty acids, alcohols, sterols, aldehyde/ketones, furans, aromatic compounds, esters, phenols, terpenes, sugar derivatives, alkaloids, and flavones. From three used concentrations (5, 10, and 15 mg/mL) of the AM gum aqueous solution, the 15 mg/mL gum solution resulted in more successful AuNP synthesis with a smaller size, which was visualized by a rusty red color appearance. UV-Visible absorption spectroscopy revealed the characteristic surface plasmon resonance (SPR) of AuNPs in aqueous solution at 540 nm. Dynamic light scattering (DLS) measurement of NPs solution revealed a hydrodynamic diameter of 162 ± 02 nm with the highest gum concentration where core AuNPs diameter was 22 ± 03 nm, recorded by Transmission electron microscopy. Zeta potential revealed fair stability of AuNPs that was not decreased with time. Catalytic activity experiments revealed that AM gum-based AuNPs can increase the rate of the reduction of methylene blue 10 times in comparison with AM gum extract alone. Results from this study showed that a diverse array of phytocompounds in AM gum can successfully reduce gold ions into gold nanoparticles, which can be used further in different pharmaceutical and industrial applications.

Biocompatible metallosurfactant-based nanocolloid-loaded Rose Bengal with excellent singlet oxygen-induced phototoxicity efficiency against cancer cells.

Photodynamic therapy (PDT) is facing challenges such as poor solubility, precise delivery, self-aggregation, and photobleaching of photosensitizers with cancer cells due to their less tendency to accumulate in tumor tissues. To address these challenges, we have explored a Rose Bengal (RB)-loaded metallocatanionic vesicles (MCVs) nanosystem for the phototoxicity of cancer cells. Different sets of MCVs were prepared by two different cationic single-chain metallosurfactants, i.e., hexadecylpyridinium trichlorocuprate (CuCPC I) and hexadecylpyridinium trichloroferrate (FeCPC I) in combination with anionic double-chain sodium bis(2-ethylhexyl)sulfosuccinate (AOT) surfactant in phosphate buffer saline of pH 7.4. The RB-loaded CuCPC I:AOT and FeCPC I:AOT vesicles enhanced the maximum singlet oxygen (1O2) generation by 1-fold and 3-fold, respectively, compared to pure RB. Upon irradiation with a 532 nm laser for 10 min, these RB-loaded CuCPC I:AOT and FeCPC I:AOT MCVs significantly decreased the metabolic activity of U-251 cells by 70% and 85% at MCVs concentration of 0.75 µM, respectively. Furthermore, RB-loaded MCVs showed the highest intracellular 1O2-mediated membrane damage and cell-killing effect as confirmed by singlet oxygen sensor green and differential nuclear staining assay, which is attributed to the cellular uptake profile of different RB-loaded MCVs fractions. Caspase 3/7 assay confirmed the apoptotic pathway of cell death by activating caspase. Therefore, the photoactivation of RB-loaded MCVs led to a significant reduction in the viability of U-251 cells (maximum 85%), which resulted in cell death. Our study demonstrated the advantage of using these dual-charge and biocompatible metallocatanionic vesicles as a promising delivery system of photodynamic therapy that can enhance 1O2 generation from PS and can be further utilized in photomedicine.

Intrinsic Permeation and Anti-Inflammatory Evaluation of Curcumin, Bisdemethoxycurcumin and Bisdemethylcurcumin by a Validated HPLC-UV Method.

Curcumin shows anti-inflammatory activity, and it has been widely investigated for neurodegenerative diseases, adjuvant treatment in AIDS and antitumor activity against different tumors, among other activities. The goal of this work was to evaluate the capacity of curcumin and its derivatives (bisdemethoxycurcumin and bisdemethylcurcumin) in preventing the irritant effects of topically applied xylol and to assess the intrinsic capacity of curcuminoids in permeating human skin by ex vivo permeation tests. Its secondary goal was to validate an HPLC method to simultaneously determine the curcuminoids in the samples from the ex vivo permeation studies and drug extraction from the skin. Curcuminoid quantification was performed using an RP-C18 column, at isocratic conditions of elution and a detection wavelength of 265 nm. The method was specific with a suitable peak resolution, as well as linear, precise, and accurate in the range of 0.195-3.125 µg/mL for the three curcuminoids. Bisdemethylcurcumin showed the greatest permeation through the human skin, and it was the curcuminoid that was most retained within the human skin. The anti-inflammatory activity of the curcuminoids was evaluated in vivo using a xylol-induced inflammation model in rats. Histological studies were performed to observe any changes in morphology at the microscopic level, and these three curcuminoids were found to be respectful within the skin structure. These results show that these three curcuminoids are suitable for anti-inflammatory formulations for dermal applications, and they can be properly quantified using HPLC-UV.

Self-Assembled Surfactant-Polyoxovanadate Soft Materials as Tuneable Vanadium Oxide Cathode Precursors for Lithium-Ion Batteries.

The mixing of [V10 O28 ]6- decavanadate anions with a dicationic gemini surfactant (gem) leads to the spontaneous self-assembly of surfactant-templated nanostructured arrays of decavanadate clusters. Calcination of the material under air yields highly crystalline, sponge-like V2 O5 (gem-V2 O5 ). In contrast, calcination of the amorphous tetrabutylammonium decavanadate allows isolation of a more agglomerated V2 O5 consisting of very small crystallites (TBA-V2 O5 ). Electrochemical analysis of the materials' performance as lithium-ion intercalation electrodes highlights the role of morphology in cathode performance. The large crystallites and long-range microstructure of the gem-V2 O5 cathode deliver higher initial capacity and superior capacity retention than TBA-V2 O5 . The smaller crystallite size and higher surface area of TBA-V2 O5 allow faster lithium insertion and superior rate performance to gem-V2 O5 .

Gemini Surfactant Mediated Catansomes for Enhanced Singlet Oxygen Generation of Rose Bengal and Their Phototoxicity against Cancer Cells.

Photodynamic therapy (PDT) is an innovative technique for cancer treatment with minimal side effects, based on the use of a photosensitizer, oxygen, and light. Photosensitizers (PSs) have several limitations, that may limit their clinical use, like poor solubilization, self-aggregation, and lack of specific targeting, which can be addressed with the use of nanomaterials. Herein, a unique type of catansomes (CaSs) was prepared using a gemini imidazolium-based surfactant (1,3-bis[(3-octadecyl-1-imidazolio)methyl]benzene dibromide (GBIB) and a double chain surfactant, diaoctyl sodium sulfosuccinate or Aerosol OT (AOT). The formation of CaS GBIB/AOT was optimized in various ethanol/water (E/W) solvent ratios by employing a facile, quick, and most reliable solution-solution mixing method. The CaS was characterized by dynamic light scattering (DLS) and field emission gun scanning electron microscopy (FEG-SEM) techniques. The experimental results reveal that stable CaSs with a spherical shape were obtained at lower concentration (100 µM). Rose Bengal (RB), a PS of the xanthene family, was incorporated into these prepared CaSs, as proven by fluorescence spectroscopy, UV-visible absorption spectroscopy, and confocal laser scanning microscopy. Singlet oxygen (1O2) generation studies revealed the relevant role of the E/W solvent ratio as there was a 4-fold boost in the 1O2 production for GBIB/AOT in E/W = 50:50 and around 3-fold in E/W = 30:70. Also, the GBIB-rich 80:20 fraction was more efficient in increasing the 1O2 generation as compared to the AOT rich fraction (20:80). Further, their phototoxicity was tested in a water-rich solvent ratio (E/W = 30:70) against MCF-7 cells. Upon irradiation with a 532 nm laser (50 mW) for 5 min, RB@GBIB/AOT(20:80) fraction caused 50% decrease in the metabolic activity of MCF-7 cells, and RB@GBIB/AOT(80:20) fraction produced a maximum 85% decrease in cell viability. Furthermore, the enhancement in intracellular 1O2 generation by RB@GBIB/AOT, as compared to pure RB, was confirmed with singlet oxygen sensor green (SOSG). This new type of CaS based on gemini surfactants exhibiting a large amount of 1O2 generation, holds great interest for several applications, such as use in photomedicine in future.

Polysilicon Microchips Functionalized with Bipyridinium-Based Cyclophanes for a Highly Efficient Cytotoxicity in Cancerous Cells.

The use of micrometric-sized vehicles could greatly improve selectivity of cytotoxic compounds as their lack of self-diffusion could maximize their retention in tissues. We have used polysilicon microparticles (SiµP) to conjugate bipyridinium-based compounds, able to induce cytotoxicity under regular intracellular conditions. Homogeneous functionalization in suspension was achieved, where the open-chain structure exhibits a more dense packing than cyclic analogues. The microparticles internalized induce high cytotoxicity per particle in cancerous HeLa cells, and the less densely packed functionalization using cyclophanes promotes higher cytotoxicity per bipy than with open-chain analogues. The self-renewing ability of the particles and their proximity to cell membranes may account for increased lipid peroxidation, achieving toxicity at much lower concentrations than that in solution and in less time, inducing highly efficient cytotoxicity in cancerous cells.

Metallocatanionic vesicle-mediated enhanced singlet oxygen generation and photodynamic therapy of cancer cells.

In clinics, photodynamic therapy (PDT) is established as a non-invasive therapeutic modality for certain types of cancers and skin disease. However, due to poor water solubility, photobleaching, and the dark toxicity of photosensitizers (PSs), further developments are required to improve the efficiency of PDT. Herein, we report the role of metallocatanionic vesicles (MCVs) in enhancing the phototoxicity of methylene blue (MB) against cancer cells. These MCVs were prepared via a facile and quick solution-solution mixing method using a cationic single-chain metallosurfactant (FeCPC I) in combination with anionic sodium oleate (Na Ol). For singlet oxygen (1O2) generation and PDT studies, two fractions of FeCPC I : Na Ol, i.e., 30 : 70 (V37) and 70 : 30 (V73), were chosen based on their long-term stability in aqueous media. A cationic PS MB was loaded into these vesicles. The MB-loaded MCV 30 : 70 and 70 : 30 fractions enhanced the 1O2 generation by 0.10- and 0.40-fold, respectively, compared with MB alone. Upon illumination using a 650 nm laser, these MB-loaded V73 and V37 MCVs significantly decreased the metabolic activity of MCF-7 cells by ≤50% at a concentration of 0.75 µM. Furthermore, the SOSG assay revealed that the synthesized MCVs enhanced the intracellular 1O2 compared with MB alone. The MB-loaded V73 MCVs showed the highest 1O2-mediated membrane damage and cell-killing effect, as confirmed using the differential nuclear staining assay (DNS), which is attributed to the cellular uptake profile of the different MCV fractions. Altogether, this work shows the advantage of using these biocompatible and dual-charge MCVs as promising delivery vehicles that can enhance the 1O2 generation from the PS. This work suggests the future application of these Fe-MCVs in magnetically guided PDT.

Intracellular Mechanical Drugs Induce Cell-Cycle Altering and Cell Death.

Current advances in materials science have demonstrated that extracellular mechanical cues can define cell function and cell fate. However, a fundamental understanding of the manner in which intracellular mechanical cues affect cell mechanics remains elusive. How intracellular mechanical hindrance, reinforcement, and supports interfere with the cell cycle and promote cell death is described here. Reproducible devices with highly controlled size, shape, and with a broad range of stiffness are internalized in HeLa cells. Once inside, they induce characteristic cell-cycle deviations and promote cell death. Device shape and stiffness are the dominant determinants of mechanical impairment. Device structural support to the cell membrane and centering during mitosis maximize their effects, preventing spindle centering, and correct chromosome alignment. Nanodevices reveal that the spindle generates forces larger than 114 nN which overcomes intracellular confinement by relocating the device to a less damaging position. By using intracellular mechanical drugs, this work provides a foundation to defining the role of intracellular constraints on cell function and fate, with relevance to fundamental cell mechanics and nanomedicine.

Light-controlled micron-scale molecular motion.

The micron-scale movement of biomolecules along supramolecular pathways, mastered by nature, is a remarkable system requiring strong yet reversible interactions between components under the action of a suitable stimulus. Responsive microscopic systems using a variety of stimuli have demonstrated impressive relative molecular motion. However, locating the position of a movable object that travels along self-assembled fibres under an irresistible force has yet to be achieved. Here, we describe a purely supramolecular system where a molecular 'traveller' moves along a 'path' over several microns when irradiated with visible light. Real-time imaging of the motion in the solvated state using total internal reflection fluorescence microscopy shows that anionic porphyrin molecules move along the fibres of a bis-imidazolium gel upon irradiation. Slight solvent changes mean movement and restructuring of the fibres giving microtoroids, indicating control of motion by fibre mechanics with solvent composition. The insight provided here may lead to the development of artificial travellers that can perform catalytic and other functions.

Integrating magnetic capabilities to intracellular chips for cell trapping.

Current microtechnologies have shown plenty of room inside a living cell for silicon chips. Microchips as barcodes, biochemical sensors, mechanical sensors and even electrical devices have been internalized into living cells without interfering their cell viability. However, these technologies lack from the ability to trap and preconcentrate cells in a specific region, which are prerequisites for cell separation, purification and posterior studies with enhanced sensitivity. Magnetic manipulation of microobjects, which allows a non-contacting method, has become an attractive and promising technique at small scales. Here, we show intracellular Ni-based chips with magnetic capabilities to allow cell enrichment. As a proof of concept of the potential to integrate multiple functionalities on a single device of this technique, we combine coding and magnetic manipulation capabilities in a single device. Devices were found to be internalized by HeLa cells without interfering in their viability. We demonstrated the tagging of a subpopulation of cells and their subsequent magnetic trapping with internalized barcodes subjected to a force up to 2.57 pN (for magnet-cells distance of 4.9 mm). The work opens the venue for future intracellular chips that integrate multiple functionalities with the magnetic manipulation of cells.

Assessing the Chemical Stability and Cytotoxicity of Electrodeposited Magnetic Mesoporous Fe-Pt Films for Biomedical Applications.

The development of feasible micro/nanoplatforms for various biomedical applications requires holistic research that explores scalable synthesis and design pathways and imposes an interdisciplinary integration of materials science, physical, medical, chemical, and biological knowledge. Thanks to their unique characteristics (i.e., structure, large specific surface areas, tuneability, versatility, and integrity), mesoporous materials have emerged as potential candidates for being part of micro/nanoplatforms for therapeutic, monitoring, and diagnostic applications. In this context, Fe-Pt mesoporous materials are excellent candidates to be part of biomedical micro/nanoplatforms, thanks to their chemical nature, structure, and magnetic properties, which endow them with magnetic locomotion, high cargo capability of therapeutic agents inside the mesoporous cavity, and large surface area for surface functionalization. However, the chemical stability in biological media and cytotoxicity of the Fe-Pt mesoporous material (without considering the effects of architecture and shape) are pivotal elements that determine the suitability of these materials for biomedical applications. This work demonstrates the following: (i) the potential of electrochemical deposition, based on the use of block copolymer micellar solutions as electrochemical media, as an easy, inexpensive, and scalable strategy to synthesize mesoporous Fe-Pt components with tunable chemical composition, porosity, magnetism, and shape (in this case films, but other architectures like nanowires can be easily fabricated using simultaneously hard templates); (ii) the excellent corrosion stability, which is comparable to bulk Au, and minimal chemical dissolution in biological media after 160 h of immersion (∼0.88% of Fe and ∼0.0019% of Pt), which confirms the robustness of Fe-Pt; and (iii) negligible cytotoxicity on HaCaT cells (human immortalized keratinocytes), which reinforces the biocompatibility of Fe-Pt mesoporous structures. Also, the presence of Fe-Pt mesoporous films seems to induce a slight increase in cell viability. These results confirm the biocompatibility of Fe-Pt mesoporous films, making them suitable for biomedical applications.

Synthesis and validation of DOPY: A new gemini dioleylbispyridinium based amphiphile for nucleic acid transfection.

Nucleic acids therapeutics provide a selective and promising alternative to traditional treatments for multiple genetic diseases. A major obstacle is the development of safe and efficient delivery systems. Here, we report the synthesis of the new cationic gemini amphiphile 1,3-bis[(4-oleyl-1-pyridinio)methyl]benzene dibromide (DOPY). Its transfection efficiency was evaluated using PolyPurine Reverse Hoogsteen hairpins (PPRHs), a nucleic acid tool for gene silencing and gene repair developed in our laboratory. The interaction of DOPY with PPRHs was confirmed by gel retardation assays, and it forms complexes of 155 nm. We also demonstrated the prominent internalization of PPRHs using DOPY compared to other chemical vehicles in SH-SY5Y, PC-3 and DF42 cells. Regarding gene silencing, a specific PPRH against the survivin gene delivered with DOPY decreased survivin protein levels and cell viability more effectively than with N-[1-(2,3-Dioleoyloxy)propyl]-N,N,N-trimethylammonium methylsulfate (DOTAP) in both SH-SY5Y and PC-3 cells. We also validated the applicability of DOPY in gene repair approaches by correcting a point mutation in the endogenous locus of the dhfr gene in DF42 cells using repair-PPRHs. All these results indicate both an efficient entry and release of PPRHs at the intracellular level. Therefore, DOPY can be considered as a new lipid-based vehicle for the delivery of therapeutic oligonucleotides.

Modulating the biological function of protein by tailoring the adsorption orientation on nanoparticles.

Protein orientation in nanoparticle-protein conjugates plays a crucial role in binding to cell receptors and ultimately, defines their targeting efficiency. Therefore, understanding fundamental aspects of the role of protein orientation upon adsorption on the surface of nanoparticles (NPs) is vital for the development of clinically important protein-based nanomedicines. In this work, new insights on the effect of the different orientation of cytochrome c (cyt c) bound to gold nanoparticles (GNPs) using various ligands on its apoptotic activity is reported. Time-of-Flight Secondary-Ion Mass Spectrometry (ToF-SIMS), electrochemical and circular dichroism (CD) analyses are used to investigate the characteristics of cyt c orientation and structure on functionalized GNPs. These studies indicate that the orientation and position of the heme ring inside the cyt c structure can be altered by changing the surface chemistry on the GNPs. A difference in the apoptosis inducing capability because of different orientation of cyt c bound to the GNPs is observed. These findings indicate that the biological activity of a protein can be modulated on the surface of NPs by varying its adsorption orientation. This study will impact on the rational design of new nanoscale biosensors, bioelectronics, and nanoparticle-protein based drugs.

Enhanced cytotoxicity of highly water-soluble gold nanoparticle-cyclopeptide conjugates in cancer cells.

Conjugation of cytostatic drugs to nanomaterials seeks to improve their low bioavailability and selectivity to overcome the important associated side effects. In this work, we aimed to synthesize water-soluble gold nanoparticles as transporters for synthetic cyclic peptides with a potential anticancer activity but with a limited bioavailability. The highly water-soluble nanoparticles (2.5 nm diameter gold core) are coated with a mixture of polyethylene glycol linkers, one bearing a terminal hydroxyl group for increasing dispersibility in water, and the second bearing a carboxylic acid group for peptide conjugation through amide bond formation. Peptide-functionalized particles have a 9.7 ± 1.8 nm hydrodynamic diameter and are highly water-soluble and stable in solution for at least one year. The morphology of the gold cores as well as their organic coating was studied using Transmission Electron Microscopy, showing that the attachment of a limited number of peptides per nanoparticle leads to a uneven organic coating of two different thicknesses, one of 2.0 ± 0.6 nm formed by polyethylene glycol linkers, and a second of 3.6 ± 0.5 nm which includes the peptide. GNP significantly enhance the internalization of the cyclic peptide BPC734 in cells as compared to peptide in solution, with improved uptake in cancerous HT29 cells. Cytotoxicity studies show that peptide BPC734 in solution is toxic in the micromolar range, whereas peptide-functionalized particles are toxic at nanomolar peptide concentrations and with a significantly higher toxicity for cancerous cells. All these results, besides the stability and expected passive tumor targeting, make these particles a promising option for improving the bioavailability, efficacy, and selectivity in cancer therapy.

π-Donor/π-Acceptor Interactions for the Encapsulation of Neurotransmitters on Functionalized Polysilicon-Based Microparticles.

Bipyridinium salts, commonly known as viologens, are π-acceptor molecules that strongly interact with π-donor compounds, such as porphyrins or amino acids, leading their self-assembling. These properties have promoted us to functionalize polysilicon microparticles with bipyridinium salts for the encapsulation and release of π-donor compounds such as catecholamines and indolamines. In this work, the synthesis and characterization of four gemini-type amphiphilic bipyridinium salts (1·4PF6-4·4PF6), and their immobilization either non-covalently or covalently on polysilicon surfaces and microparticles have been achieved. More importantly, they act as hosts for the subsequent incorporation of π-donor neurotransmitters such as dopamine, serotonin, adrenaline or noradrenaline. Ultraviolet-visible absorption and fluorescence spectroscopies and high-performance liquid chromatography were used to detect the formation of the complex in solution. The immobilization of bipyridinium salts and neurotransmitter incorporation on polysilicon surfaces was corroborated by contact angle measurements. The reduction in the bipyridinium moiety and the subsequent release of the neurotransmitter was achieved using ascorbic acid, or Vitamin C, as a triggering agent. Quantification of neurotransmitter encapsulated and released from the microparticles was performed using high-performance liquid chromatography. The cytotoxicity and genotoxicity studies of the bipyridinium salt 1·4PF6, which was selected for the non-covalent functionalization of the microparticles, demonstrated its low toxicity in the mouse fibroblast cell line (3T3/NIH), the human liver carcinoma cell line (HepG2) and the human epithelial colorectal adenocarcinoma cell line (Caco-2).

Controlling the preferential motion of chiral molecular walkers on a surface.

Molecular walkers standing on two or more "feet" on an anisotropic periodic potential of a crystal surface may perform a one-dimensional Brownian motion at the surface-vacuum interface along a particular direction in which their mobility is the largest. In thermal equilibrium the molecules move with equal probabilities both ways along this direction, as expected from the detailed balance principle, well-known in chemical reactivity and in the theory of molecular motors. For molecules that possess an asymmetric potential energy surface (PES), we propose a generic method based on the application of a time-periodic external stimulus that would enable the molecules to move preferentially in a single direction thereby acting as Brownian ratchets. To illustrate this method, we consider a prototypical synthetic chiral molecular walker, 1,3-bis(imidazol-1-ylmethyl)-5(1-phenylethyl)benzene, diffusing on the anisotropic Cu(110) surface along the Cu rows. As unveiled by our kinetic Monte Carlo simulations based on the rates calculated using ab initio density functional theory, this molecule moves to the nearest equivalent lattice site via the so-called inchworm mechanism in which it steps first with the rear foot and then with the front foot. As a result, the molecule diffuses via a two-step mechanism, and due to its inherent asymmetry, the corresponding PES is also spatially asymmetric. Taking advantage of this fact, we show how the external stimulus can be tuned to separate molecules of different chirality, orientation and conformation. The consequences of these findings for molecular machines and the separation of enantiomers are also discussed.

Correction: Controlling the preferential motion of chiral molecular walkers on a surface.

[This corrects the article DOI: 10.1039/C9SC01135H.].

Nanostructured supramolecular hydrogels: Towards the topical treatment of Psoriasis and other skin diseases.

Supramolecular hydrogels were synthesized using a bis-imidazolium based amphiphile, and incorporating chemically diverse drugs, such as the cytostatics gemcitabine hydrochloride and methotrexate sodium salt, the immunosuppressive drug tacrolimus, as well as the corticoid drugs betamethasone 17-valerate and triamcinolone acetonide, and their potential as drug delivery agents in the dermal treatment of Psoriasis was evaluated. The rheological behavior of gels was studied, showing in all cases suitable viscoelastic properties for topical drug delivery. Scanning electron microscopy (SEM) shows that the drugs included have a great influence on the gel morphology at the microscopic level, as the incorporation of gemcitabine hydrochloride leads to slightly thicker fibers, the incorporation of tacrolimus induces flocculation and spherical precipitates, and the incorporation of methotrexate forms curled fibers. 1H NMR spectroscopy experiments show that these drugs not only remain dissolved at the interstitial space, but up to 72% of either gemcitabine or methotrexate, and up to 38% of tacrolimus, is retained within the gel fibers in gels formed with a 1:1 gelator:drug molar ratio. This unique fiber incorporation not only protects the drug from degradation, but also importantly induces a Two Phase Exponential drug release, where the first phase corresponds to the drug dissolved in the interstitial space, while the second phase corresponds to the drug exiting from the gel fibers, and where the speed in each phase is in accordance with the physicochemical properties of the drugs, opening perspectives for controlled delivery. Skin permeation ex vivo tests show how these gels successfully promote the drug permeation and retention inside the skin for reaching their therapeutic target, while in vivo experiments demonstrate that they decrease the hyperplasia and reduce the macroscopic tissue damage typically observed in psoriatic skin, significantly more than the drugs in solution. All these characteristics, beside the spontaneous and easy preparation (room temperature and soft stirring), make these gels a good alternative to other routes of administration for Psoriasis treatment, increasing the drug concentration at the target tissue, and minimizing side effects.