Quorum sensing communication between lipid-based artificial cells.

Population behavior based on quorum sensing communication is a key property of living microorganisms. Here, we show quorum sensing behavior in an artificial cell population consisting of giant lipid vesicles loaded with sender-receiver machinery (enzymes and responsive biomolecules). Our system allows the examination of the collective output based on cell density, fuel concentration and proximity, which are important factors controlling natural quorum sensing behavior.

Drug Delivery Nanosystems for the Localized Treatment of Glioblastoma Multiforme.

Glioblastoma multiforme is one of the most prevalent and malignant forms of central nervous system tumors. The treatment of glioblastoma remains a great challenge due to its location in the intracranial space and the presence of the blood⁻brain tumor barrier. There is an urgent need to develop novel therapy approaches for this tumor, to improve the clinical outcomes, and to reduce the rate of recurrence and adverse effects associated with present options. The formulation of therapeutic agents in nanostructures is one of the most promising approaches to treat glioblastoma due to the increased availability at the target site, and the possibility to co-deliver a range of drugs and diagnostic agents. Moreover, the local administration of nanostructures presents significant additional advantages, since it overcomes blood⁻brain barrier penetration issues to reach higher concentrations of therapeutic agents in the tumor area with minimal side effects. In this paper, we aim to review the attempts to develop nanostructures as local drug delivery systems able to deliver multiple agents for both therapeutic and diagnostic functions for the management of glioblastoma.

Lectin-gated and glycan functionalized mesoporous silica nanocontainers for targeting cancer cells overexpressing Lewis X antigen.

Gated mesoporous silica nanoparticles can deliver payload upon the application of a predefined stimulus, and therefore are promising drug delivery systems. Despite their important role, relatively low emphasis has been placed on the design of gating systems that actively target carbohydrate tumor cell membrane receptors. We describe herein a new Lewis X (Lex) antigen-targeted delivery system comprising mesoporous silica nanoparticles (MSNs) loaded with ATTO 430LS dye, functionalized with a Lex derivative (1) and capped with a fucose-specific carbohydrate-binding protein (Aleuria aurantia lectin (AAL)). This design takes advantage of the affinity of AAL for Lex overexpressed receptors in certain cancer cells. In the proximity of the cells, AAL is detached from MSNs to bind Lex, and selectins in the cells bind Lex in the gated MSNs, thereby inducing cargo delivery. Gated MSNs are nontoxic to colon cancer DLD-1 cells, and ATTO 430LS dye delivered correlated with the amount of Lex antigen overexpressed at the DLD-1 cell surface. This is one of the few examples of MSNs using biologically relevant glycans for both capping (via interaction with AAL) and targeting (via interaction with overexpressed Lex at the cell membrane).

Multi-channel receptors based on thiopyrylium functionalised with macrocyclic receptors for the recognition of transition metal cations and anions.

We report herein the synthesis and characterization of a family of ligands containing different cation binding sites covalently connected to a thiopyrylium signalling reporter. The receptors L1-L6 are able to signal the presence of certain metal cations via three different channels; i.e. electrochemically, fluorogenically and chromogenically. An acetonitrile solution of L1-L6 shows a bright blue colour due to a charge-transfer band in the 575-585 nm region. The colour variation in acetonitrile of L1-L6 in the presence of the metal cations Ag+, Cd2+, Cu2+, Fe3+, Hg2+, Ni2+, Pb2+ and Zn2+ has been studied. A selective hypsochromic shift of the blue band was found for the systems L4-Pb2+ and L5-Hg2+. Additionally, L1-L6 are poorly fluorescent but coordination with certain metal cations induces an enhancement of the fluorescence at ca 500 nm. For instance, the presence of Cu2+ and Fe3+ induced a remarkable 42-fold and 45-fold enhancement in the emission intensity of L1 centred at 500 nm, respectively. Also remarkable was the 18-fold enhancement observed for L4 and L5 in the presence of Fe3+ and Cu2+, respectively. The electrochemical behaviour of receptors L1-L6 was studied in acetonitrile using platinum as a working electrode and [Bu4N][BF4] as a supporting electrolyte. This family of receptors showed a one-electron reversible redox process at ca. -0.46 V versus sce attributed to the reduction of the thiopyrylium group. A moderate anodic shift in the presence of certain metal cations was observed. The effect in the UV-visible spectra of acetonitrile solutions of receptor L1-L6 in the presence of anions was also studied. A remarkable bleaching was found in the presence of cyanide.

Ferrocene-cyclam: a redox-active macrocycle for the complexation of transition metal ions and a study on the influence of the relative permittivity on the coulombic interaction between metal cations.

The reaction of 1,1'-ferrocene-bis(methylenepyridinium) salt with 1,4,8,11-tetraazacyclotetradecane-5,12-dione, followed by LiAlH4 reduction results in the formation of FcCyclam. Metal complexes of FcCyclam with M2+ = Co2+, Ni2+, Cu2+, and Zn2+ were synthesized from FcCyclam and the respective metal triflates. The complexation of Cu2+ and FcCyclam in CH3CN is preceeded by a rapid electron transfer, followed by a slower complex formation reaction and a reverse electron transfer. The protonation constants of FcCyclam and the stability constants for the Cu2+ complex of FcCyclam (logK = 9.26(4) for the formation of the [Cu(FcCyclam)]2+ complex) were determined in 1,4-dioxane/water 70:30 v/v, 0.1 moldm(-3), KNO3, 25 degrees C. By using FcCyclam one can selectively sense the presence of Cu2+ ions in the presence of Ni2+, Zn2+, Cd2+, Hg2+, and Pb2+ with a very large deltaE approximately 200 mV, depending on pH. The X-ray crystal structures of FcCyclam and of complexes with Co2+, Ni2+, Cu2+, and Zn2+ were determined and Fe-M2+ distances obtained: Fe-Co2+ 395.9, Fe-Ni2+ 385.4, Fe-Cu2+ 377.7, and Fe-Zn2+ 369.0 pm. The redox potential of FcCyclam is influenced in a characteristic manner by the complexation of M2+. A linear correlation of 1/r approximately/= deltaE [r = distance Fe-M2+ from crystal data, deltaE=-E1/2([M(FcCyclam)]2+) - E1/2(FcCyclam)] was found; this is indicative of a mainly Coulomb type interaction between the two metal centers. The nature of the Fe...M2+ interaction was also investigated by determining deltaE in several solvents (mixtures) of different dielectric constants epsilon. The expected relation of deltaE approximately/= 1/epsilon was only found at very high values of epsilon. At epsilon < 40 increased ion-pairing appears to reduce the effective positive charge at M2+ leading to progessively smaller values of deltaE with lowered epsilon. The dependence of deltaE and epsilon can be calculated semiquantitatively by combining the Fuoss ion-pairing theory with the Coulomb model.

1,3,5-Triarylpent-2-en-1,5-diones for the colorimetric sensing of the mercuric cation.

The 1,3,5-triarylpent-2-en-1,5-dione group selectively undergoes cyclisation and changes its colour from yellow to magenta upon coordination of Hg2+ on a remote site.

Oxidative decarboxylation of naproxen.

The decarboxylation of naproxen (1H) and its salt (1-) was achieved by means of chemical [Ce(IV) or S2O8(2-)] and electrochemical oxidation. The product patterns were compatible with mechanisms involving single-electron transfer from the pi-system or the carboxylate moiety. The results are discussed in connection with the involvement of electron-transfer processes in the reported phototoxicity of naproxen.