Search

Without timely treatment, poor wound healing in corneal injuries can seriously impair vision and lead to blindness. Thus, it is vital to develop a therapeutic strategy to accelerate corneal re-epithelialization. The conjugation of self-assembled motifs with a fibronectin-mimetic peptide sequence (PHSRN) drastically improves the chemical stability of PHSRN against protease hydrolysis and minimally affects its biological activity to promote the migration of corneal epithelial cells. The optimized Nap-FFPHSRN self-assembled into bioactive supramolecular hydrogels increases cell motility by remolding F-actin and boosts the tight junction of the corneal epithelium by increasing the expression of zonula occludens-1 (ZO-1). An in vivo experiment showed that a Nap-FFPHSRN hydrogel provided extended precorneal retention with good ocular tolerance after topical instillation. An animal model of corneal scrape showed that a single daily dose of Nap-FFPHSRN hydrogel had a superior therapeutic effect in facilitating corneal re-epithelialization with complete morphological and architectural recovery. With a rational approach to mimic bioactive proteins, this study presents a new strategy to demonstrate the potential of peptide-based supramolecular hydrogels for use in clinical treatment of corneal injury. Here we systematically investigate the self-assembly behavior and chemical stability of designed peptide amphiphiles (Nap-FPHRSN, Nap-FFPHSRN and Nap-FFFPHSRN). The introduction of self-assembled motifs (Nap-F, Nap-FF and Nap-FFF) drastically enhances the chemical stability of fibronectin-mimetic peptide (PHSRN). Moreover, topical instillation of Nap-FFPHSRN hydrogel once daily, exhibits a better in vivo effect than PHSRN and the same in vivo effect as fibronectin, both of which are instilled three times daily, for promoting full morphological and architectural recovery after corneal re-epithelialization. As a rational design of conjugating bioactive peptides with self-assembled motifs to mimic bioactive proteins, this work may lead to a new approach that improves the in vivo therapeutic effect for treating corneal injury in clinic settings. [Display omitted] [ABSTRACT FROM AUTHOR]

Peptide‐drug conjugates (PDCs) are an important class of therapeutic agents that combine one or more active molecules with a short peptide via a biodegradable spacer to generate prodrugs. Here an antioxidant (i.e., 3,5‐dihydroxybenzoic acid), a non‐steroidal anti‐inflammatory drug (i.e., ibuprofen, IPF), and a self‐assembled peptide motif (i.e., Gly‐Phe‐Phe‐Tyr‐Asp, GFFYD) are integrated to produce a peptide‐drug amphiphile, which self‐assembles to form hydrogel and further exerts the synergistic effects, and consequently emerges high therapeutic efficacy. In the in vitro study toward lipopolysaccharide‐activated RAW264.7 macrophages, the resulting hydrogel significantly reduces the production of cytokines (e.g., IL‐1β, IL‐6 and tumor necrosis factor‐α (i.e., TNF‐α)) compared with that of native IPF via the inhibition of nuclear factor‐κB (i.e., NF‐κB), janus kinase‐signal transducer and activator of transcription (i.e., JAK‐STAT) signals and NLR family pyrin domain containing 3 (i.e., NLRP3) inflammasome activation. Moreover, a rabbit model of endotoxin induced uveitis evidences the superior therapeutic efficacy of the resulting hydrogel over that of clinically used 0.1 wt% diclofenac sodium eyedrop. Overall, this work offers new insights into the anti‐inflammatory mechanism of PDCs hydrogel and presents the therapeutic values in the treatment of ocular disorders, and ultimately fulfils the potential clinical benefits of PDCs. [ABSTRACT FROM AUTHOR]

Changing an oxygen atom of the phosphoester bond in phosphopeptides by a sulfur atom enables instantly targeting Golgi apparatus (GA) and selectively killing cancer cells by enzymatic self‐assembly. Specifically, conjugating cysteamine S‐phosphate to the C‐terminal of a self‐assembling peptide generates a thiophosphopeptide. Being a substrate of alkaline phosphatase (ALP), the thiophosphopeptide undergoes rapid ALP‐catalyzed dephosphorylation to form a thiopeptide that self‐assembles. The thiophosphopeptide enters cells via caveolin‐mediated endocytosis and macropinocytosis and instantly accumulates in GA because of dephosphorylation and formation of disulfide bonds in Golgi by themselves and with Golgi proteins. Moreover, the thiophosphopeptide potently and selectively inhibits cancer cells (HeLa) with the IC50 (about 3 μM), which is an order of magnitude more potent than that of the parent phosphopeptide. [ABSTRACT FROM AUTHOR]

Herein, we report that assemblies of nucleopeptides selectively sequester ATP in complex conditions (for example, serum and cytosol). We developed assemblies of nucleopeptides that selectively sequester ATP over ADP. Counteracting enzymes interconvert ATP and ADP to modulate the nanostructures formed by the nucleopeptides and the nucleotides. The nucleopeptides, sequestering ATP effectively in cells, slow down efflux pumps in multidrug‐resistant cancer cells, thus boosting the efficacy of doxorubicin, an anticancer drug. Investigation of 11 nucleopeptides (including d‐ and l‐enantiomers) yields five more nucleopeptides that differentiate ATP and ADP through either precipitation or gelation. As the first example of assemblies of nucleopeptides that interact with ATP and disrupt intracellular ATP dynamics, this work illustrates the use of supramolecular assemblies to interact with small and essential biological molecules for controlling cell behavior. [ABSTRACT FROM AUTHOR]

The development of highly efficient catalysts for the selective oxidation of styrene to benzaldehyde has attracted great attention in recent years because of its significance in synthetic chemistry. In this study, two different kinds of copper-based metal oxide nanoparticles (NPs), namely, CuO and CuO/Co3O4 NPs, were synthesized by a simple and scalable method, and these nanoparticles demonstrated efficient catalytic abilities for the selective oxidation of styrene and its derivatives to the corresponding aldehydes in the presence of tert-butyl hydroperoxide (TBHP) under mild reaction conditions in excellent yields. Importantly, both of the heterogeneous catalysts can be recycled up to five runs while still maintaining their high catalytic activity. [ABSTRACT FROM AUTHOR]

[Display omitted] The modulation of inflammation is effective to treat many ocular surface diseases. Thus the low bioavailability of common anti-inflammatory eye-drops urges the development of ocular drug delivery systems to extend the ocular retention and enhance the cellular uptake for improving anti-inflammatory effect of eye-drops. Here we covalently conjugate two molecules of clinically anti-inflammatory drug (i.e. , dexamethasone) with a small peptide (i.e. , Tyr–Glu–Asn–Pro–Thr–Tyr) to generate an anti-inflammatory hydrogel eye-drop. With a self-assembled ability, the designed supramolecular hydrogel achieves gel–sol–gel transition by varying shearing forces which increases the pre-corneal retention of drug. The fluorescent imaging reveals the efficient cellular uptake of designed conjugate via clathrin-mediated endocytosis. A rodent model of endotoxin-induced uveitis verifies that the supramolecular hydrogel eye-drop suppresses inflammation responses without ocular irritation. As a rational approach to design anti-inflammatory drugs as eye-drops, this work overcomes the frequent instillation of clinical eye-drops and further improves the bioavailability of anti-inflammatory drugs, which may provide an effective and household way to fight ocular surface inflammation. [ABSTRACT FROM AUTHOR]