RESUMEN
Achieving spatiotemporal control of molecular self-assembly associated with actuation of biological functions inside living cells remains a challenge owing to the complexity of the cellular environments and the lack of characterization tools. We present, for the first time, the organelle-localized self-assembly of a peptide amphiphile as a powerful strategy for controlling cellular fate. A phenylalanine dipeptide (FF) with a mitochondria-targeting moiety, triphenyl phosphonium (Mito-FF), preferentially accumulates inside mitochondria and reaches the critical aggregation concentration to form a fibrous nanostructure, which is monitored by confocal laser scanning microscopy and transmission electron microscopy. The Mito-FF fibrils induce mitochondrial dysfunction via membrane disruption to cause apoptosis. The organelle-specific supramolecular system provides a new opportunity for therapeutics and in-depth investigations of cellular functions.Spatiotemporal control of intracellular molecular self-assembly holds promise for therapeutic applications. Here the authors develop a peptide consisting of a phenylalanine dipeptide with a mitochondrial targeting moiety to form self-assembling fibrous nanostructures within mitochondria, leading to apoptosis.
Asunto(s)
Muerte Celular/fisiología , Mitocondrias/metabolismo , Péptidos/metabolismo , Animales , Apoptosis , Línea Celular , Células HeLa , Humanos , Ratones , Péptidos/síntesis química , Péptidos/genética , Transporte de Proteínas , Especies Reactivas de OxígenoRESUMEN
A simple peptide based prodrug of camptothecin (CPT) has been synthesised in which the CPT is conjugated to a tripeptide (KCK) via a disulfide linkage (KCK-CPT) and self-assembled into well-defined nanostructures in water depending on the concentration. The hyaluronic acid (HA) complex of KCK-CPT exhibited target specific toxicity with excellent antitumour efficiency.
Asunto(s)
Antineoplásicos/administración & dosificación , Ácido Hialurónico/química , Nanoestructuras , Péptidos/administración & dosificación , Microscopía ConfocalRESUMEN
The electrochemical performance of Li-ion batteries (LIBs) can be highly tuned by various factors including the morphology of the anode material, the nature of the electrolyte, the binding material, and the percentage of conducting materials. Binding materials have been of particular interest to researchers over the decades as a means to further improve the cycle durability and columbic efficiency of LIBs. Such approaches include the introduction of different polymeric binders such as poly(acrylic acid) (PAA), carboxymethyl cellulose (CMC), and alginic acid (Alg) into the Si anode of LIBs. To achieve a better efficiency of LIBs, herein, we introduce a novel copolymer, poly(tert-butyl acrylate-co-triethoxyvinylsilane) (TBA-TEVS), as an efficient binder with stable cycle retention and excellent specific capacity. The binder forms a highly interconnected three-dimensional network upon thermal treatment as a result of de-protection of the tert-butyl group and the consequent inter-intra condensation reaction, which minimizes pulverization of the Si nanoparticles. Moreover, the siloxane group is expected to promote the formation of stable solid-electrolyte-interface (SEI) layers. A series of random copolymers were synthesized by varying the molar ratio of tert-butyl acrylate and triethoxyvinylsilane. Twenty-one percent of TEVS in the TBS-TEVS copolymer gave rise to a superior performance as a binder for Si anodes, where the anodes showed a stable specific capacity of 2551 mA h g(-1) over hundreds of cycles and an initial columbic efficiency (ICE) of 81.8%.