Bioadhesive supramolecular hydrogel from unprotected, short d,l-peptides with Phe-Phe and Leu-Asp-Val motifs.

The uncapped tripeptide DPhe-Phe-Leu acts as self-assembly template to yield supramolecular hydrogel biomaterials. As an example, self-assembling DPhe-Phe-Leu-Asp-Val contains the LDV bioadhesive motif for β1 integrin activation. Hydrogels made of the two peptides successfully mimic fibronectin of the extracellular matrix and lead to high cell viability, adhesion, and spreading.

Direct Visualization of the Structural Transformation between the Lyotropic Liquid Crystalline Lamellar and Bicontinuous Cubic Mesophase.

The transition between the lyotropic liquid crystalline lamellar and the bicontinuous cubic mesophase drives multiple fundamental cellular processes involving changes in cell membrane topology, including endocytosis and membrane budding. While several theoretical models have been proposed to explain this dynamic transformation, experimental validation of these models has been challenging because of the short-lived nature of the intermediates present during the phase transition. Herein, we report the direct observation of a lamellar-to-bicontinuous cubic phase transition in nanoscale dispersions using a combination of cryogenic transmission electron microscopy and static small-angle X-ray scattering.

Controlling self-assembly of diphenylalanine peptides at high pH using heterocyclic capping groups.

Using small angle neutron scattering (SANS), it is shown that the existence of pre-assembled structures at high pH for a capped diphenylalanine hydrogel is controlled by the selection of N-terminal heterocyclic capping group, namely indole or carbazole. At high pH, changing from a somewhat hydrophilic indole capping group to a more hydrophobic carbazole capping group results in a shift from a high proportion of monomers to self-assembled fibers or wormlike micelles. The presence of these different self-assembled structures at high pH is confirmed through NMR and circular dichroism spectroscopy, scanning probe microscopy and cryogenic transmission electron microscopy.

Incorporation of antimicrobial peptides in nanostructured lipid membrane mimetic bilayer cubosomes.

The inverse bicontinuous lipidic cubic phase offers a simple and robust membrane mimetic with the ability to encapsulate peptides, potentially increasing bioavailability, while also offering a platform from which functionalized, targeted nanoparticles can be developed. Herein we have investigated the use of a number of cubic phase nanoparticle systems with encapsulated antimicrobial peptides gramicidin A', melittin, and alamethicin. The optimal peptide loading ranges, over which cubic symmetry was retained, were determined using small angle X-ray scattering.

Dual-modality NIRF-MRI cubosomes and hexosomes: High throughput formulation and in vivo biodistribution.

Engineered nanoparticles with multiple complementary imaging modalities are of great benefit to the rapid treatment and diagnosis of disease in various organs. Herein, we report the formulation of cubosomes and hexosomes that carry multiple amphiphilic imaging contrast agents in their self-assembled lipid bilayers. This is the first report of the use of both near infrared fluorescent (NIRF) imaging and gadolinium lipid based magnetic resonance (MR) imaging modalities in cubosomes and hexosomes.

Apolipoprotein A-II Plus Lipid Emulsion Enhance Cell Growth via SR-B1 and Target Pancreatic Cancer In Vitro and In Vivo.

Background: Apolipoprotein A-II (ApoA-II) is down regulated in the sera of pancreatic ductal adenocarcinoma (PDAC) patients, which may be due to increase utilization of high density lipoprotein (HDL) lipid by pancreatic cancer tissue. This study examined the influence of exogenous ApoA-II on lipid uptake and cell growth in pancreatic cancer (PC) both in vitro and in vivo.

Methods: Cryo transmission electron microscopy (TEM) examined ApoA-II's influence on morphology of SMOFLipid emulsion.

Gd-DTPA-Dopamine-Bisphytanyl Amphiphile: Synthesis, Characterisation and Relaxation Parameters of the Nanoassemblies and Their Potential as MRI Contrast Agents.

Here, a new amphiphilic magnetic resonance imaging (MRI) contrast agent, a Gd(III)-chelated diethylenetriaminepentaacetic acid conjugated to two branched alkyl chains via a dopamine spacer, Gd-DTPA-dopamine-bisphytanyl (Gd-DTPA-Dop-Phy), which is readily capable of self-assembling into liposomal nanoassemblies upon dispersion in an aqueous solution, is reported. In vitro relaxivities of the dispersions were found to be much higher than Magnevist, a commercially available contrast agent, at 0.47 T but comparable at 9.

Lipid-PEG conjugates sterically stabilize and reduce the toxicity of phytantriol-based lyotropic liquid crystalline nanoparticles.

Lyotropic liquid crystalline nanoparticle dispersions are of interest as delivery vectors for biomedicine. Aqueous dispersions of liposomes, cubosomes, and hexosomes are commonly stabilized by nonionic amphiphilic block copolymers to prevent flocculation and phase separation. Pluronic stabilizers such as F127 are commonly used; however, there is increasing interest in using chemically reactive stabilizers for enhanced functionalization and specificity in therapeutic delivery applications.

Structural characterization by transmission electron microscopy and immunoreactivity of recombinant Hendra virus nucleocapsid protein expressed and purified from Escherichia coli.

Hendra virus (family Paramyxoviridae) is a negative sense single-stranded RNA virus (NSRV) which has been found to cause disease in humans, horses, and experimentally in other animals, e.g. pigs and cats.

First Direct Observation of Stable Internally Ordered Janus Nanoparticles Created by Lipid Self-Assembly.

We present the first observation of Janus nanoparticles consisting of stable, coexisting ordered mesophases in discrete particles created by lipid self-assembly. Cryo-TEM images provided visual identification of the multicompartment Janus nanoparticles and, combined with SAXS data, confirmed the presence of mixed cubic phases and mixed cubic/hexagonal phases within individual nanoparticles. We further investigated computer visualization models to interpret the potential interface between the interconnected coexisting nanostructured domains within a single nanoparticle.

Colloidally stabilized magnetic carbon nanotubes providing MRI contrast in mouse liver tumors.

The use of medical imaging contrast agents may lead to improved patient prognosis by potentially enabling an earlier detection of diseases and therefore an earlier initiation of treatments. In this study, we fabricated superparamagnetic iron oxide (SPIO) nanoparticles within the inner cavity of multiwalled carbon nanotubes (MWCNTs) for the first time; thereby ensuring high mechanical stability of the nanoparticles. A simple, but effective, self-assembled coating with RAFT diblock copolymers ensured the SPIO-MWCNTs have a high dispersion stability under physiological conditions.

Evaluation of Gd-DTPA-monophytanyl and phytantriol nanoassemblies as potential MRI contrast agents.

Supramolecular self-assembling amphiphiles have been widely used in drug delivery and diagnostic imaging. In this report, we present the self-assembly of Gd (III) chelated DTPA-monophytanyl (Gd-DTPA-MP) amphiphiles incorporated within phytantriol (PT), an inverse bicontinuous cubic phase forming matrix at various compositions. The dispersed colloidal nanoassemblies were evaluated as potential MRI contrast agents at various magnetic field strengths.

Epidermal growth factor receptor-targeted lipid nanoparticles retain self-assembled nanostructures and provide high specificity.

Next generation drug delivery utilising nanoparticles incorporates active targeting to specific sites. In this work, we combined targeting with the inherent advantages of self-assembled lipid nanoparticles containing internal nano-structures. Epidermal growth factor receptor (EGFR)-targeting, PEGylated lipid nanoparticles using phytantriol and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-PEG-maleimide amphiphiles were created.

Application of positron annihilation lifetime spectroscopy (PALS) to study the nanostructure in amphiphile self-assembly materials: phytantriol cubosomes and hexosomes.

Self-assembled amphiphile nanostructures of colloidal dimensions such as cubosomes and hexosomes are of interest as delivery vectors in pharmaceutical and nanomedicine applications. Translation would be assisted through a better of understanding of the effects of drug loading on the internal nanostructure, and the relationship between this nanostructure and drug release profile. Positron annihilation lifetime spectroscopy (PALS) is sensitive to local microviscosity and is used as an in situ molecular probe to examine the Q2 (cubosome) → H2 (hexosome) → L2 phase transitions of the pharmaceutically relevant phytantriol-water system in the presence of a model hydrophobic drug, vitamin E acetate (VitEA).

Packing and mobility of hydrocarbon chains in phospholipid lyotropic liquid crystalline lamellar phases and liposomes: characterisation by positron annihilation lifetime spectroscopy (PALS).

Lipid lamellar mesophases and their colloidal dispersions (liposomes) are increasingly being deployed in vivo as drug delivery vehicles, and also as models of biological membranes in fundamental biophysics studies. The permeability and diffusion of small molecules such as drugs is accommodated by a change in local curvature and molecular packing (mesophase behaviour) of the bilayer membrane molecules. Positron annihilation lifetime spectroscopy (PALS) is capable of providing in situ molecular level information on changes in free volume and void space arising from such changes in a non-perturbative manner.

Understanding the photothermal heating effect in non-lamellar liquid crystalline systems, and the design of new mixed lipid systems for photothermal on-demand drug delivery.

Lipid-based liquid crystalline systems are showing potential as stimuli-responsive nanomaterials, and NIR-responsive gold nanoparticles have been demonstrated to provide control of transitions in non-lamellar phases. In this study, we focus on a deeper understanding of the photothermal response of both lamellar and non-lamellar phases, and new systems formed by alternative lipid systems not previously reported, by linking the photothermal heating to the bulk thermal properties of the materials. Dynamic photothermal studies were performed using NIR laser irradiation and monitoring the structural response using time resolved small angle X-ray scattering for the bulk phases and hexosomes.

Novel RAFT amphiphilic brush copolymer steric stabilisers for cubosomes: poly(octadecyl acrylate)-block-poly(polyethylene glycol methyl ether acrylate).

Copolymers, particularly Pluronics®, are typically used to sterically stabilise colloidal nanostructured particles composed of a lyotropic liquid crystalline bicontinuous cubic phase (cubosomes). There is a need to design and assess new functionalisable stabilisers for these colloidal drug delivery systems. Six amphiphilic brush copolymers, poly(octadecyl acrylate)-block-poly(polyethylene glycol methyl ether acrylate) (P(ODA)-b-P(PEGA-OMe)), synthesised by reversible addition-fragmentation chain transfer (RAFT), were assessed as novel steric stabilisers for cubosomes.

Nitroxide-loaded hexosomes provide MRI contrast in vivo.

The purpose of this work was to synthesize and screen, for their effectiveness to act as T1-enhancing magnetic resonance imaging (MRI) contrast agents, a small library of nitroxide lipids incorporated into cubic-phase lipid nanoparticles (cubosomes). The most effective nitroxide lipid was then formulated into lower-toxicity lipid nanoparticles (hexosomes), and effective MR contrast was observed in the aorta and spleen of live rats in vivo. This new class of lower-toxicity lipid nanoparticles allowed for higher relaxivities on the order of those of clinically used gadolinium complexes.

Gadolinium-DTPA amphiphile nanoassemblies: agents for magnetic resonance imaging and neutron capture therapy.

Engineering biocompatible and physiologically stable nanoscaled therapeutics and imaging agents with the ability to target tumor tissue is a key challenge for the advancement of cancer therapeutics and diagnostic imaging. Here, we present chelating amphiphiles with the capacity to form nanoassembled colloidal particles containing high payloads of gadolinium (Gd) ions. We present the in situ synthesis and complexation of Gd with colloidal nanoassemblies (NAs) based on diethylenetriamine pentaacetic acid (DTPA) amphiphiles.

Nanoassemblies of Gd-DTPA-monooleyl and glycerol monooleate amphiphiles as potential MRI contrast agents.

Self-assembly of lipid-based amphiphiles into various supramolecular nanostructured particles has been used in creating novel nanomaterials with diverse applications in drug delivery and diagnostic imaging. Here we report on Gd(iii) chelated DTPA amphiphiles with an oleyl chain (Gd-DTPA-MO) incorporated within the self-assembly matrix of glycerol monooleate (GMO), an inverse cubic phase forming system, at varying compositions. The dispersed colloidal nanoassemblies were explored for their potential as magnetic resonance imaging (MRI) contrast agents.

Water-dispersible magnetic carbon nanotubes as T2-weighted MRI contrast agents.

An efficient MRI T2-weighted contrast agent incorporating a potential liver targeting functionality was synthesized via the combination of superparamagnetic iron oxide (SPIO) nanoparticles with multiwalled carbon nanotubes (MWCNTs). Poly(diallyldimethylammonium chloride) (PDDA) was coated on the surface of acid treated MWCNTs via electrostatic interactions and SPIO nanoparticles modified with a potential targeting agent, lactose-glycine adduct (Lac-Gly), were subsequently immobilized on the surface of the PDDA-MWCNTs. A narrow magnetic hysteresis loop indicated that the product displayed superparamagnetism at room temperature which was further confirmed by ZFC (zero field cooling)/FC (field cooling) curves measured by SQUID.

Layer-by-layer polymer coating on discrete particles of cubic lyotropic liquid crystalline dispersions (cubosomes).

Cubic phase lyotropic liquid crystalline colloidal dispersions (cubosomes) were surface-modified with seven polyelectrolyte layers using a layer-by-layer (LbL) approach. The first layer consisted of a copolymer synthesized from methacrylic acid and oleoyl methacrylate for enhanced incorporation within the bilayer of the cubic nanostructure. Six additional layers of poly(L-lysine) and poly(methacrylic acid) were then sequentially added, followed by a washing procedure to remove polymer aggregates from the soft matter particles.

Nanofibrillar micelles and entrapped vesicles from biodegradable block copolymer/polyelectrolyte complexes in aqueous media.

Here we report a viable route to fibrillar micelles and entrapped vesicles in aqueous solutions. Nanofibrillar micelles and entrapped vesicles were prepared from complexes of a biodegradable block copolymer poly(ethylene oxide)-block-poly(lactide) (PEO-b-PLA) and a polyelectrolyte poly(acrylic acid) (PAA) in aqueous media and directly visualized using cryogenic transmission electron microscopy (cryo-TEM). The self-assembly and the morphological changes in the complexes were induced by the addition of PAA/water solution into the PEO-b-PLA in tetrahydrofuran followed by dialysis against water.

Ammonium hydroxide treatment of Aβ produces an aggregate free solution suitable for biophysical and cell culture characterization.

Alzheimer's disease is the leading cause of dementia in the elderly. Pathologically it is characterized by the presence of amyloid plaques and neuronal loss within the brain tissue of affected individuals. It is now widely hypothesised that fibrillar structures represent an inert structure.

Self-assembly of ciprofloxacin and a tripeptide into an antimicrobial nanostructured hydrogel.

This work reports the self-assembly of a sparingly soluble antibiotic (ciprofloxacin) and a hydrophobic tripeptide ((D)Leu-Phe-Phe) into supramolecular nanostructures that yield a macroscopic hydrogel at physiological pH. Drug incorporation results in modified morphology and rheological properties of the self-assembled hydrogel. These changes can be correlated with intermolecular interactions between the drug and the peptide, as confirmed by spectroscopic analysis (fluorescence, circular dichroism, IR).