Biodegradable Polymersomes with Structure Inherent Fluorescence and Targeting Capacity for Enhanced Photo-Dynamic Therapy.

Biodegradable nanostructures displaying aggregation-induced emission (AIE) are desirable from a biomedical point of view, due to the advantageous features of loading capacity, emission brightness, and fluorescence stability. Herein, biodegradable polymers comprising poly (ethylene glycol)-block-poly(caprolactone-gradient-trimethylene carbonate) (PEG-P(CLgTMC)), with tetraphenylethylene pyridinium-TMC (PAIE) side chains have been developed, which self-assembled into well-defined polymersomes. The resultant AIEgenic polymersomes are intrinsically fluorescent delivery vehicles. The presence of the pyridinium moiety endows the polymersomes with mitochondrial targeting ability, which improves the efficiency of co-encapsulated photosensitizers and improves therapeutic index against cancer cells both in vitro and in vivo. This contribution showcases the ability to engineer AIEgenic polymersomes with structure inherent fluorescence and targeting capacity for enhanced photodynamic therapy.

Fluorescent Metallacage-Core Supramolecular Polymer Gel Formed by Orthogonal Metal Coordination and Host-Guest Interactions.

Herein, we report the preparation of a multifunctional metallacage-core supramolecular gel by orthogonal metal coordination and host-guest interactions. A tetragonal prismatic cage with four appended 21-crown-7 (21C7) moieties in its pillar parts was first prepared via the metal-coordination-driven self-assembly of cis-Pt(PEt3)2(OTf)2, tetraphenylethene (TPE)-based sodium benzoate ligands and linear dipyridyl ligands. Further addition of a bisammonium linker to the cage delivered a supramolecular polymer network via the host-guest interactions between the 21C7 moieties and ammonium salts, which formed a supramolecular gel at relatively higher concentrations. Due to the incorporation of a TPE derivative as the fluorophore, the gel shows emission properties. Multiple stimuli responsiveness and good self-healing properties were also observed because of the dynamic metal coordination and host-guest interactions used to stabilize the whole network structure. Moreover, the storage and loss moduli of the gel are 10-fold those of the gel without the metallacage cores, indicating that the rigid metallacage plays a significant role in enhancing the stiffness of the gel. The studies described herein not only enrich the functionalization of fluorescent metallacages via elegant ligand design but also provide a way to prepare stimuli-responsive and self-healing supramolecular gels as robust and smart materials.

Development of a new EPR spin trap, DOD-8C (N-[4-dodecyloxy-2-(7'-carboxyhept-1'-yloxy)benzylidene]-N-tert-butylamine N-oxide), for the trapping of lipid radicals at a predetermined depth within biological membranes.

We report on the development of the first member of a new family of EPR spin-trapping agents designed to trap radicals at a predetermined depth within biological membranes. By analogy to the use of nitroxide spin labels to 'report' on the environment at specific depths within biological membranes, we set out to prepare similar reporter molecules, but with a nitrone in place of the nitroxide function. The prototype compounds were tested in a model system consisting of large unilamellar vesicles exposed to a copper-dependent radical generating system. This entailed the reduction of tert-butylhydroperoxide to the tert-butoxyl radical ((t)BuO(.-)) by a membrane-permeable Cu(I) complex, which was generated in situ by reduction of the Cu(II) complex by ascorbate. To assist in the identification of the radicals detected, preliminary studies were performed in methanolic solution, where the major radical trapped was shown to be (.-)CH(2)OH, resulting from H-atom abstraction from the alcohol by (t)BuO(.-). This conclusion was shown to be in agreement with predictions based on chemical kinetics, which were then used to support the proposal that the primary species trapped in the lipid vesicles were radicals derived from membrane fatty acids. This molecule represents the first of a new generation of spin traps which, through modification, can be used to position the radical-trapping nitrone moiety at chosen depths within biological membranes.

Antiallergic agents. IV - Substituted 2-benzylidene-3(2H)-benzofuranone-5-carboxylic acids.

A series of substituted 2-benzylidene-3(2H)-benzofuranone-5-carboxylic acids were synthetized and tested for antiallergic activity by the passive cutaneous anaphylactic reaction in the rat. Many compounds display an antiallergic activity comparable to that of disodium chromoglycate when administered parenterally: in addition some derivatives are effective when given by mouth.