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.

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 .

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.

Multifunctional Serine Protease Inhibitor-Coated Water-Soluble Gold Nanoparticles as a Novel Targeted Approach for the Treatment of Inflammatory Skin Diseases.

The overexpression and increased activity of the serine protease Kallikrein 5 (KLK5) is characteristic of inflammatory skin diseases such as Rosacea. The use of inhibitors of this enzyme-such as 4-(2-aminoethyl)benzenesulfonyl fluoride hydrochloride (AEBSF·HCl) or the anti-human recombinant Kallikrein 5 (anti-KLK5) antibody-in the treatment of the disease has been limited due to their low bioavailability, for which their immobilization in drug delivery agents can contribute to making serine protease inhibitors clinically useful. In this work, we synthesized gold nanoparticles (GNP) coated with a mixture of hydroxyl- and carboxyl-terminated thiolates (GNP.OH/COOH), whose carboxyl groups were used to further functionalize the nanoparticles with the serine protease inhibitor AEBSF·HCl either electrostatically or covalently (GNP.COOH AEBSF and GNP.AEBSF, respectively), or with the anti-KLK5 antibody (GNP.antiKLK5). The synthesized and functionalized GNP were highly water-soluble, and they were extensively characterized using UV-vis absorption spectroscopy, Transmission Electron Microscopy (TEM), Dynamic Light Scattering (DLS), and Thermogravimetric Analysis (TGA). GNP.OH/COOH and their subsequent functionalizations effectively inhibited KLK5 in vitro. Internalization of fluorophore-coated GNP.OH/COOH in human keratinocytes (HaCaT cells) was proven using confocal fluorescence microscopy. Cell viability assays revealed that the cytotoxicity of free AEBSF is importantly decreased when it is incorporated in the nanoparticles, either ionically (GNP.COOH AEBSF) or, most importantly, covalently (GNP.AEBSF). The functionalized nanoparticles GNP.AEBSF and GNP.antiKLK5 inhibited intracellular KLK5 activity in HaCaT cells and diminished secretion of IL-8 under inflammatory conditions triggered by TLR-2 ligands. This study points to the great potential of these GNP as a new intracellular delivery strategy for both small drugs and antibodies in the treatment of skin diseases such as Rosacea.

Photosensitiser-gold nanoparticle conjugates for photodynamic therapy of cancer.

Gold nanoparticles (AuNPs) have been extensively studied within biomedicine due to their biocompatibility and low toxicity. In particular, AuNPs have been widely used to deliver photosensitiser agents for photodynamic therapy (PDT) of cancer. Here we review the state-of-the-art for the functionalisation of the gold nanoparticle surface with both photosensitisers and targeting ligands for the active targeting of cancer cell surface receptors. From the initial use of the AuNPs as a simple carrier of the photosensitiser for PDT, the field has significantly advanced to include: the use of PEGylated modification to provide aqueous compatibility and stealth properties for in vivo use; gold metal-surface enhanced singlet oxygen generation; functionalisation of the AuNP surface with biological ligands to specifically target over-expressed receptors on the surface of cancer cells and; the creation of nanorods and nanostars to enable combined PDT and photothermal therapies. These versatile AuNPs have significantly enhanced the efficacy of traditional photosensitisers for both in vitro and in vivo cancer therapy. From this review it is apparent that AuNPs have an important future in the treatment of cancer.

Piezoelectric tuning fork biosensors for the quantitative measurement of biomolecular interactions.

The quantitative measurement of biomolecular interactions is of great interest in molecular biology. Atomic force microscopy (AFM) has proved its capacity to act as a biosensor and determine the affinity between biomolecules of interest. Nevertheless, the detection scheme presents certain limitations when it comes to developing a compact biosensor. Recently, piezoelectric quartz tuning forks (QTFs) have been used as laser-free detection sensors for AFM. However, only a few studies along these lines have considered soft biological samples, and even fewer constitute quantified molecular recognition experiments. Here, we demonstrate the capacity of QTF probes to perform specific interaction measurements between biotin-streptavidin complexes in buffer solution. We propose in this paper a variant of dynamic force spectroscopy based on representing adhesion energies E (aJ) against pulling rates v (nm s(-1)). Our results are compared with conventional AFM measurements and show the great potential of these sensors in molecular interaction studies.

Highly conductive single-molecule wires with controlled orientation by coordination of metalloporphyrins.

Porphyrin-based molecular wires are promising candidates for nanoelectronic and photovoltaic devices due to the porphyrin chemical stability and unique optoelectronic properties. An important aim toward exploiting single porphyrin molecules in nanoscale devices is to possess the ability to control the electrical pathways across them. Herein, we demonstrate a method to build single-molecule wires with metalloporphyrins via their central metal ion by chemically modifying both an STM tip and surface electrodes with pyridin-4-yl-methanethiol, a molecule that has strong affinity for coordination with the metal ion of the porphyrin. The new flat configuration resulted in single-molecule junctions of exceedingly high lifetime and of conductance 3 orders of magnitude larger than that obtained previously for similar porphyrin molecules but wired from either end of the porphyrin ring. This work presents a new concept of building highly efficient single-molecule electrical contacts by exploiting metal coordination chemistry.

A small molecule walks along a surface between porphyrin fences that are assembled in†situ.

An on-surface bimolecular system is described, comprising a simple divalent bis(imidazolyl) molecule that is shown to "walk" at room temperature via an inchworm mechanism along a specific pathway terminated at each end by oligomeric "fences" constructed on a monocrystalline copper surface. Scanning tunneling microscopy shows that the motion of the walker occurs along the [110] direction of the Cu surface with remarkably high selectivity and is effectively confined by the orthogonal construction of covalent porphyrin oligomers along the [001] surface direction, which serve as barriers. Density functional theory shows that the mobile molecule walks by attaching and detaching the nitrogen atoms in its imidazolyl "legs" to and from the protruding close-packed rows of the metal surface and that it can transit between two energetically equivalent extended and contracted conformations by overcoming a small energy barrier.

Barcode tagging of human oocytes and embryos to prevent mix-ups in assisted reproduction technologies.

STUDY QUESTION: Is the attachment of biofunctionalized polysilicon barcodes to the outer surface of the zona pellucida an effective approach for the direct tagging and identification of human oocytes and embryos during assisted reproduction technologies (ARTs)? SUMMARY ANSWER: The direct tagging system based on lectin-biofunctionalized polysilicon barcodes of micrometric dimensions is simple, safe and highly efficient, allowing the identification of human oocytes and embryos during the various procedures typically conducted during an assisted reproduction cycle. WHAT IS KNOWN ALREADY: Measures to prevent mismatching errors (mix-ups) of the reproductive samples are currently in place in fertility clinics, but none of them are totally effective and several mix-up cases have been reported worldwide. Using a mouse model, our group has previously developed an effective direct embryo tagging system which does not interfere with the in vitro and in vivo development of the tagged embryos. This system has now been tested in human oocytes and embryos. STUDY DESIGN, SIZE, DURATION: Fresh immature and mature fertilization-failed oocytes (n = 21) and cryopreserved day 1 embryos produced by in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) (n = 205) were donated by patients (n = 76) undergoing ARTs. In vitro development rates, embryo quality and post-vitrification survival were compared between tagged (n = 106) and non-tagged (control) embryos (n = 99). Barcode retention and identification rates were also calculated, both for embryos and for oocytes subjected to a simulated ICSI and parthenogenetic activation. Experiments were conducted from January 2012 to January 2013. PARTICIPANTS/MATERIALS, SETTING, METHODS: Barcodes were fabricated in polysilicon and biofunctionalizated with wheat germ agglutinin lectin. Embryos were tagged with 10 barcodes and cultured in vitro until the blastocyst stage, when they were either differentially stained with propidium iodide and Hoechst or vitrified using the Cryotop method. Embryo quality was also analyzed by embryo grading and time-lapse monitoring. Injected oocytes were parthenogenetically activated using ionomycin and 6-dimethylaminopurine. MAIN RESULTS AND THE ROLE OF CHANCE: Blastocyst development rates of tagged (27/58) and non-tagged embryos (24/51) were equivalent, and no significant differences in the timing of key morphokinetic parameters and the number of inner cell mass cells were detected between the two groups (tagged: 24.7 ± 2.5; non-tagged: 22.3 ± 1.9), indicating that preimplantation embryo potential and quality are not affected by the barcodes. Similarly, re-expansion rates of vitrified-warmed tagged (19/21) and non-tagged (16/19) blastocysts were similar. Global identification rates of 96.9 and 89.5% were obtained in fresh (mean barcode retention: 9.22 ± 0.13) and vitrified-warmed (mean barcode retention: 7.79 ± 0.35) tagged embryos, respectively, when simulating an automatic barcode reading process, though these rates were increased to 100% just by rotating the embryos during barcode reading. Only one of the oocytes lost one barcode during intracytoplasmic injection (100% identification rate) and all oocytes retained all the barcodes after parthenogenetic activation. LIMITATIONS, REASONS FOR CAUTION: Although the direct embryo tagging system developed is effective, it only allows the identification and traceability of oocytes destined for ICSI and embryos. Thus, the traceability of all reproductive samples (oocytes destined for IVF and sperm) is not yet ensured. WIDER IMPLICATIONS OF THE FINDINGS: The direct embryo tagging system developed here provides fertility clinics with a novel tool to reduce the risk of mix-ups in human ARTs. The system can also be useful in research studies that require the individual identification of oocytes or embryos and their individual tracking. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by the Sociedad Española de Fertilidad, the Spanish Ministry of Education and Science (TEC2011-29140-C03) and the Generalitat de Catalunya (2009SGR-00282 and 2009SGR-00158). The authors do not have any competing interests.

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.

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.

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.

Efficient biofunctionalization of polysilicon barcodes for adhesion to the zona pellucida of mouse embryos.

Cell tracking is an emergent area in nanobiotechnology, promising the study of individual cells or the identification of populations of cultured cells. In our approach, microtools designed for extracellular tagging are prepared, because using biofunctionalized polysilicon barcodes to tag cell membranes externally avoids the inconveniences of cell internalization. The crucial covalent biofunctionalization process determining the ultimate functionality was studied in order to find the optimum conditions to link a biomolecule to a polysilicon barcode surface using a self-assembled monolayer (SAM) as the connector. Specifically, a lectin (wheat germ agglutinin, WGA) was used because of its capacity to recognize some specific carbohydrates present on the surface of most mammalian cells. Self-assembled monolayers were prepared on polysilicon surfaces including aldehyde groups as terminal functions to study the suitability of their covalent chemical bonding to WGA. Some parameters, such as the polysilicon surface roughness or the concentration of WGA, proved to be crucial for successful biofunctionalization and bioactivity. The SAMs were characterized by contact angle measurements, time-of-flight secondary ion mass spectrometry (TOF-SIMS), laser desorption/ionization time-of-flight mass spectrometry (LDI-TOF MS), and atomic force microscopy (AFM). The biofunctionalization step was also characterized by fluorescence microscopy and, in the case of barcodes, by adhesion experiments to the zona pellucida of mouse embryos. These experiments showed high barcode retention rates after 96 h of culture as well as high embryo viability to the blastocyst stage, indicating the robustness of the biofunctionalization and, therefore, the potential of these new microtools to be used for cell tagging.

Gemini imidazolium amphiphiles for the synthesis, stabilization, and drug delivery from gold nanoparticles.

Gold nanoparticles (AuNPs) are considered useful vehicles for medical therapy and diagnosis. Despite the progress made in this field, there is need to find direct, reliable, and versatile synthetic procedures for their preparation as well as new multifunctional coating agents. In this sense, we have explored the use of imidazolium amphiphiles to prepare new AuNPs designed for anion recognition and transport. Thus, in this work we describe (a) the synthesis, by a phase transfer method, of new gold nanoparticles using gemini-type surfactants as ligands based on imidazolium salts, those ligands acting as transfer agents into organic media and also as nanoparticle stabilizers, (b) the examination of their stability in solution, (c) the chemical and physical characterization of the nanoparticles, using a variety of techniques, including UV-visible spectroscopy (UV-vis), transmission electron microscopy (TEM), and X-ray photoelectron spectroscopy (XPS), (d) toxicity data concerning both the imidazolium ligands and the imidazolium coated nanoparticles, (e) the assessment of their molecular recognition ability toward molecules of biological interest, such as anions and carboxylate containing model drugs, such as ibuprofen, (f) the study of their toxicity and those of their coating ligands, as well as their ability for cell internalization, and (g) the study of their ability for delivering anionic pharmaceuticals. The structurally governed triple role of those new gemini-type surfactants is responsible for the preparation, remarkable stability, and delivery properties of these functional AuNPs.

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.

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.

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.

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.