Vesicles formed in water by synthetic macro-amphiphiles have attracted much attention as nanocontainers having properties that extend the physical and chemical limits of liposomes. We sought to develop ABA block copolymeric amphiphiles that self-assemble into unilamellar vesicles that can be further oxidatively destabilized. We selected poly(ethylene glycol) (PEG) as the hydrophilic A blocks, owing to its resistance to protein adsorption and low toxicity. As hydrophobic B blocks, we selected poly(propylene sulphide) (PPS), owing to its extreme hydrophobicity, its low glass-transition temperature, and most importantly its oxidative conversion from a hydrophobe to a hydrophile, poly(propylene sulphoxide) and ultimately poly(propylene sulphone). This is the first example of the use of oxidative conversions to destabilize such carriers. This new class of oxidation-responsive polymeric vesicles may find applications as nanocontainers in drug delivery, biosensing and biodetection.

OLED Fabrication and Measurements: Pre-patterned indium tin oxide (ITO) substrates with an effective individual device area of 3.14 mm 2 were cleaned by sonication in a detergent solution for 3 min and then washed with large amount of doubly distilled water. Further sonication in ethanol for 3 min followed before blowing dry with a stream of nitrogen. The ITO substrates were then treated with O 2 plasma for one minute before being loaded into the vacuum chamber. The organic layers were deposited thermally at a rate of 0.1± 0.3 nm s ±1 under a pressure of~2 10 ±5 torr in an Ulvac Cryogenic deposition system. An alloy of Mg and Ag (ca. 10:1, 50 nm) was deposited as the cathode, which was capped with 100 nm of Ag. The current±voltage±luminance was measured in ambient with a Keithley 2400 Source meter and a Newport 1835C Optical meter equipped with 818ST silicon photodiode [19] The related Ir(piq) 3 complex was briefly mentioned in a recent conference paper by S. Ohada and co-workers. The device based on this complex gave a maximum bightness 10 000 cd m ±2 at J = 365 mA cm [20] The red iridium phosphors in this study have a 1-(phenyl)isoquinoline framework. In our new findings, iridium complexes bearing a 3-(phenyl)-isoquinoline framework also show an efficient yellow phosphorescence emission (565 nm) with a maximum brightness 65 000 cd m Cell-Responsive Synthetic Hydrogels** By Matthias P. Lutolf, George P. Raeber, Andreas H. Zisch, Nicola Tirelli, and Jeffrey A. Hubbell* An important part of tissue function relies on the dynamic dialog that exists between cells and their extracellular matrices (ECM): the ECM is active, presenting bound adhesion sites that interact with cell-surface receptors, [1] and it is responsive to signals presented by cells, locally degrading under the influence of proteases at the surface of the migrating cell.[2±4] While artificial biomaterial matrices used in cell culture and tissue engineering have been developed to be responsive to physical [5±9] and even biochemical [10±14] stimuli, they do not widely address this concept of responsiveness to cellular stimuli. We mimicked these features in synthetic hydrogel networks, for application in both cell biology and tissue engineering, [15±17] incorporating pendant receptor-binding sites so that cells can exert traction [18] and crosslinking protease-sensitive degradation sites so that cells can create a path to enable forward movement. [19] Our results demonstrate that synthetic materials can be responsive to cellular influences in vitro and in vivo, including here, as an example, inducing and responding to angiogenic invasion. We formed polymer networks in situ using conjugate addition reactions. We linked molecular building blocks performing either structural (poly(ethylene glycol), PEG) or biological (oligopeptides) function (Scheme 1). Vinyl sulfone (VS)-functionalized multiarmed telechelic PEG macromers reacted with thiolate groups of cysteine-containing peptides by conjugate addition, [20] a reaction that is highly selective versus b...

A quantitative structure-reactivity relationship for the Michael-type addition of thiols onto acrylates was determined. Several thiol-containing peptides were investigated by examining the correlation between the second-order rate constant of their addition onto PEG-diacrylate and the pK(a) of the thiols within a peptide. By introducing charged amino acids in close proximity to a cysteine, the pK(a) of the thiol was systematically modulated by electrostatic interactions. Positive charges from the amino acid arginine decreased the pK(a) of the thiol and accelerated the reaction with acrylates while negative charges from aspartic acids showed the opposite effect. A linear correlation between thiolate concentrations and kinetic constants was found, confirming the role of thiolates as the reactive species in this Michael-type reaction. The relevant factors influencing the reactivity were the sign and the number of the neighboring charges, while the position of these charges had little effect on reactivity. These results provide a basis for the rational design of peptides, where the kinetics and thus selectivity of protein/peptide conjugation with polymeric structures via Michael-type addition reactions can be controlled.

We have designed oxidation-responsive vesicles from synthetic amphiphilic block copolymers ("polymersomes") of ethylene glycol and propylene sulfide. Thioethers in the hydrophobic poly(propylene sulfide) block are converted into the more hydrophilic sulfoxides and sulfones upon exposure to an oxidative environment, changing the hydrophilic-lipophilic balance of the macroamphiphile and thus inducing its solubilization. Here we sought to explore generation of the oxidative environment and induction of polymersome destabilization through production of hydrogen peroxide by the glucose-oxidase (GOx)/glucose/oxygen system. We studied the encapsulation of GOx within polymersomes, its stability and activity, and glucose-triggered polymersome destabilization. Stimulus-responsive polymersomes may find applications as nanocontainers in sensing devices and as drug delivery systems.

Three optimised nanoparticles have been developed (two uncoated and one HA-coated) and their toxicity on fibroblasts and macrophages has been evaluated: experiments showed the beneficial character of HA-coating in the reduction of toxicity (IC50 raised from 0.7-0.8 mg/mL to 1.8 mg/mL) and suggested that the uncoated chitosan/TPP nanoparticles had toxic effects following internalisation rather than membrane disruption.

No abstract

Alkanethiolates have been widely used as chemisorbates to modify gold surfaces, in spite of their relatively poor oxidative stability. We introduce gold-chemisorbing block copolymers bearing an anchoring block of poly(propylene sulphide) (PPS), selected in the expectation of greater stability. These materials offer a more robust approach to surface modification of gold. As an example, a triblock copolymer with poly(ethylene glycol) (PEG) was selected, with the goal of minimizing biological adsorption and adhesion. The copolymer PEG17-bl-PPS25-bl-PEG9 chemisorbed to form a dense monolayer of 226 +/- 26 ng cm(-2), approximately 2.2 nm thick. The copolymeric adlayer was much more stable to oxidation than commonly used alkanethiolates. Its presence greatly reduced protein adsorption (>95%), even after exposure to whole blood serum (>55 mg x ml(-1)), as well as cell adhesion over long culture durations (>97%). PPS-containing copolymers are an attractive alternative to alkanethiolates, and PEG-bl-PPS-bl-PEG presents a powerful example for use in biodiagnostic and bioanalytical devices.

We have recently demonstrated the possible use of organic polysulfides for the design of oxidation-sensitive colloidal carriers in the form of polymeric vesicles, which are particularly suitable for the encapsulation of hydrosoluble drugs. In the present research we extend our efforts to carriers specifically suitable for hydrophobic molecules. Exploiting the living emulsion polymerization of episulfides, we have produced new cross-linked polysulfide nanoparticles. Here we demonstrate how this process allows the production of stable nanoparticles with a good control over their size and functionality. The nanoparticles showed negligible cytotoxicity on a fibroblast model; furthermore, they exhibited sensitivity to oxidative conditions, which first produce swelling and then solubilize the material.