QCM-D Investigations on Cholesterol-DNA Tethering of Liposomes to Microbubbles for Therapy.

Lipid-shelled microbubbles (MBs) offer potential as theranostic agents, capable of providing both contrast enhancement in ultrasound imaging as well as a route for triggered drug release and improved localized drug delivery. A common motif in the design of such therapeutic vehicles is the attachment of the drug carrier, often in the form of liposomes, to the microbubble. Traditionally, such attachments have been based around biotin-streptavidin and maleimide-PDP chemistries. Comparatively, the use of DNA-lipid tethers offers potential advantage. First, their specificity permits the construction of more complex architectures that might include bespoke combinations of different drug-loaded liposomes and/or targeting groups, such as affimers or antibodies. Second, the use of dual-lipid tether strategies should increase the strength of the individual tethers tethering the liposomes to the bubbles. The ability of cholesterol-DNA (cDNA) tethers for conjugation of liposomes to supported lipid bilayers has previously been demonstrated. For in vivo applications, bubbles and liposomes often contain a proportion of polyethylene glycol (PEG) to promote stealth-like properties and increase lifetimes. However, the associated steric effects may hinder tethering of the drug payload. We show that while the presence of PEG reduced the tethering affinity, cDNA can still be used for the attachment of liposomes to a supported lipid bilayer (SLB) as measured via QCM-D. Importantly, we show, for the first time, that QCM-D can be used to study the tethering of microbubbles to SLBs using cDNA, signified by a decrease in the magnitude of the frequency shift compared to liposomes alone due to the reduced density of the MBs. We then replicate this tethering interaction in the bulk and observe attachment of liposomes to the shell of a central MB and hence formation of a model therapeutic microbubble.

Synthesis of near-infrared absorbing triangular Au nanoplates using biomineralisation peptides.

Triangular Au nanoplates (TrAuNPls) possessing strong plasmonic properties can be used as photothermal agents in cancer therapy. However, the controlled preparation of such morphologies typically requires harsh synthetic conditions. Biomolecules offer an alternative route to developing biocompatible synthetic protocols. In particular, peptides offer a novel route for inorganic synthesis under ambient conditions. Herein, using the previously isolated peptide, ASHQWAWKWE, for Au nanoparticle (AuNP) synthesis, the conditions for preparing TrAuNPls via a one-pot synthetic process of mixing HAuCl4 and peptides at room temperature were investigated to effectively obtain particles possessing near-infrared absorbance for non-invasive optical diagnosis and phototherapy. By adjusting the peptide concentration, the size and property of TrAuNPls were controlled under neutral pH conditions. The synthesised particles showed potential as photothermal therapeutic agents in vitro. In addition, peptide characterisation using B3 derivatives revealed the importance of the third amino acid histidine in morphological regulation and potential circular Au nanoplates (AuNPl) synthesis with ASEQWAWKWE and ASAQWAWKWE peptides. These findings provide not only an easy and green synthetic method for TrAuNPls and circular AuNPls, but also some insight to help elucidate the regulation of peptide-based nanoparticle synthesis for use in cancer therapy. STATEMENT OF SIGNIFICANCE: Biological molecules have received increasing attention as a vehicle to synthesise inorganic materials with specific properties under ambient conditions; particularly, short peptides have the potential to control the synthesis of nanoscale materials with tailored functions. Here, the application of a previously isolated peptide was assessed in synthesising Au nanoparticles containing decahedral and triangular nanoplates with near-infrared absorbance. The size and absorbance peaks of the triangular nanoplates observed were peptide concentration-dependent. In addition, these fine-tuned triangular nanoplates exhibited potential as a phototherapeutic agent. Moreover, the peptide derivatives indicated the possibility of synthesising circular nanoplates. These findings may offer insight into development of new techniques for synthesising functional nanoparticles having biological applications using non-toxic molecules under mild conditions stituted in the original B3 peptide is underlined.

Stimuli-Responsive Release of Antimicrobials Using Hybrid Inorganic Nanoparticle-Associated Drug-Delivery Systems.

Recently, the combination of metallic nanoparticles (NPs) of Au, Ag, Fe2 O3 , and Fe3 O4 with traditional soft matter drug-delivery systems has emerged as a promising strategy to achieve site-specific and controlled release of antimicrobial agents. By harnessing the plasmonic and magnetic properties of inorganic NPs, the disruption of antibiotic-loaded liposomes, polymersomes, and hydrogels can be remotely triggered by mechanisms such as photo- and magneto-thermal effects, microbubble cavitation, magnetic positioning, and pH-changes, hence offering significant advantages in improving antibacterial efficacy, reducing side effects, and in overcoming antimicrobial resistance. This review highlights the latest development of stimuli-responsive antibiotic delivery systems incorporating inorganic NPs. The methods employed for preparation of hybrid inorganic NP-associated drug-delivery systems and the effects this has upon the system are discussed. Finally, a detailed exposition of the NP-mediated triggering mechanisms is provided and pertinent examples of their use in antimicrobial applications are presented.

One-step fabrication of hollow-channel gold nanoflowers with excellent catalytic performance and large single-particle SERS activity.

Hollow metallic nanostructures have shown potential in various applications including catalysis, drug delivery and phototherapy, owing to their large surface areas, reduced net density, and unique optical properties. In this study, novel hollow gold nanoflowers (HAuNFs) consisting of an open hollow channel in the center and multiple branches/tips on the outer surface are fabricated for the first time, via a facile one-step synthesis using an auto-degradable nanofiber as a bifunctional template. The one-dimensional (1D) nanofiber acts as both a threading template as well as a promoter of the anisotropic growth of the gold crystal, the combination of which leads to the formation of HAuNFs with a hollow channel and nanospikes. The synergy of favorable structural/surface features, including sharp edges, open cavity and high-index facets, provides our HAuNFs with excellent catalytic performance (activity and cycling stability) coupled with large single-particle SERS activity (including ∼30 times of activity in ethanol electro-oxidation and ∼40 times of single-particle SERS intensity, benchmarked against similar-sized solid gold nanospheres with smooth surfaces, as well as retaining 86.7% of the initial catalytic activity after 500 cycles in ethanol electro-oxidation). This innovative synthesis gives a nanostructure of the geometry distinct from the template and is extendable to fabricating other systems for example, hollow-channel silver nanoflowers (HAgNFs). It thus provides an insight into the design of hollow nanostructures via template methods, and offers a versatile synthetic strategy for diverse metal nanomaterials suited for a broad range of applications.

Minimal F-actin cytoskeletal system for planar supported phospholipid bilayers.

Preferential binding of F-actin to lipid bilayers containing ponticulin was investigated on both planar supported bilayers and on a cholesterol-based tethering system. The transmembrane protein ponticulin in Dictyostelium discoideum is known to provide a direct link between the actin cytoskeleton and the cell membrane ( Wuestehube, L. J. ; Luna, E. J. J. Cell Biol. 1987, 105, 1741- 1751 ). Purification of ponticulin has allowed an in vitro model of the F-actin cytoskeletal scaffold system to be formed and investigated by AFM, epi-fluorescence microscopy, surface plasmon resonance (SPR), and quartz crystal microbalance with dissipation (QCM-D). Single filament features of F-actin bound to the ponticulin containing lipid bilayer are shown by AFM to have a pitch of 37.3 +/- 1.1 nm and a filament height of 7.0 +/- 1.6 nm. The complementary techniques of QCM-D and SPR were used to obtain dissociation constants for the interaction of F-actin with ponticulin containing bilayers, giving 10.5 +/- 1.7 microM for a physisorbed bilayer and 10.8 +/- 3.6 microM for a tethered bilayer, respectively.