Centre for Bionano Interactions (CBNI) Research Collection

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Now showing 1 - 5 of 30
  • Publication
    Structure-dynamics correlations in composite PF127-PEG-based hydrogels; cohesive/hydrophobic interactions determine phase and rheology and identify the role of micelle concentration in controlling 3D extrusion printability
    A library of composite polymer networks (CPNs) were formed by combining Pluronic F127, as the primary gelator, with a range of di-acrylate functionalised PEG polymers, which tune the rheological properties and provide UV crosslinkability. A coarse-grained sol–gel room temperature phase diagram was constructed for the CPN library, which identifies PEG-dependent disruption of micelles as leading to liquefication. Small angle X-ray scattering and rheological measurements provide detailed insight into; (i) micelle-micelle ordering; (ii) micelle-micelle disruption, and; (iii) acrylate-micelle disruption; with contributions that depend on composition, including weak PEG chain length and end group effects. The influence of composition on 3D extrusion printability through modulation of the cohesive/hydrophobic interactions was assessed. It was found that only micelle content provides consistent changes in printing fidelity, controlled largely by printing conditions (pressure and feed rate). Finally, the hydrogels were shown to be UV photo-crosslinkable, which further improves fidelity and structural integrity, and usefully reduces the mesh size. Our results provide a guide for design of 3D-printable CPN inks for future biomedical applications.
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  • Publication
    Impact of dynamic sub-populations within grafted chains on the protein binding and colloidal stability of PEGylated nanoparticles
    Polyethylene glycol grafting has played a central role in preparing the surfaces of nano-probes for biological interaction, to extend blood circulation times and to modulate protein recognition and cellular uptake. However, the role of PEG graft dynamics and conformation in determining surface recognition processes is poorly understood primarily due to the absence of a microscopic picture of the surface presentation of the polymer. Here a detailed NMR analysis reveals three types of dynamic ethylene glycol units on PEG-grafted SiO2 nanoparticles (NPs) of the type commonly evaluated as long-circulating theranostic nano-probes; a narrow fraction with fast dynamics associated with the chain ends; a broadened fraction spectrally overlapped with the former arising from those parts of the chain experiencing some dynamic restriction; and a fraction too broad to be observed in the spectrum arising from units closer to the surface/graft which undergo slow motion on the NMR timescale. We demonstrate that ethylene glycol units transition between fractions as a function of temperature, core size, PEG chain length and surface coverage and demonstrate how this distribution affects colloidal stability and protein uptake. The implications of the findings for biological application of grafted nanoparticles are discussed in the context of accepted models for surface ligand conformation. This journal is
      11Scopus© Citations 8
  • Publication
    Long-circulating magnetoliposomes as surrogates for assessing pancreatic tumour permeability and nanoparticle deposition
    Nanocarriers are candidates for cancer chemotherapy delivery, with growing numbers of clinically-approved nano-liposomal formulations such as Doxil® and Onivyde® (liposomal doxorubicin and irinotecan) providing proof-of-concept. However, their complex biodistribution and the varying susceptibility of individual patient tumours to nanoparticle deposition remains a clinical challenge. Here we describe the preparation, characterisation, and biological evaluation of phospholipidic structures containing solid magnetic cores (SMLs) as an MRI-trackable surrogate that could aid in the clinical development and deployment of nano-liposomal formulations. Through the sequential assembly of size-defined iron oxide nanoparticle clusters with a stabilizing anionic phospholipid inner monolayer and an outer monolayer of independently-selectable composition, SMLs can mimic physiologically a wide range of nano-liposomal carrier compositions. In patient-derived xenograft models of pancreatic adenocarcinoma, similar tumour deposition of SML and their nano-liposomal counterparts of identical bilayer composition was observed in vivo, both at the tissue level (fluorescence intensities of 1.5 × 108 ± 1.8 × 107 and 1.2 × 108 ± 6.3 × 107, respectively; ns, 99% confidence interval) and non-invasively using MR imaging. We observed superior capabilities of SML as a surrogate for nano-liposomal formulations as compared to other clinically-approved iron oxide nano-formulations (ferumoxytol). In combination with diagnostic and therapeutic imaging tools, SMLs have high clinical translational potential to predict nano-liposomal drug carrier deposition and could assist in stratifying patients into treatment regimens that promote optimal tumour deposition of nanoparticulate chemotherapy carriers. Statement of significance: Solid magnetoliposomes (SMLs) with compositions resembling that of FDA-approved agents such as Doxil® and Onivyde® offer potential application as non-invasive MRI stratification agents to assess extent of tumour deposition of nano-liposomal therapeutics prior to administration. In animals with pancreatic adenocarcinoma (PDAC), SML-PEG exhibited (i) tumour deposition comparable to liposomes of the same composition; (ii) extended circulation times, with continued tumour deposition up to 24 hours post-injection; and (iii) MRI capabilities to determine tumour deposition up to 1 week post-injection, and confirmation of patient-to-patient variation in nanoparticulate deposition in tumours. Hence SMLs with controlled formulation are a step towards non-invasive MRI stratification approaches for patients, enabled by evaluation of the extent of deposition in tumours prior to administration of nano-liposomal therapeutics.
      5Scopus© Citations 4
  • Publication
    Classification and biological identity of complex nano shapes
    Everywhere in our surroundings we increasingly come in contact with nanostructures that have distinctive complex shape features on a scale comparable to the particle itself. Such shape ensembles can be made by modern nano-synthetic methods and many industrial processes. With the ever growing universe of nanoscale shapes, names such as “nanoflowers” and “nanostars” no longer precisely describe or characterise the distinct nature of the particles. Here we capture and digitise particle shape information on the relevant size scale and create a condensed representation in which the essential shape features can be captured, recognized and correlated. We find the natural emergence of intrinsic shape groups as well-defined ensemble distributions and show how these may be analyzed and interpreted to reveal novel aspects of our nanoscale shape environment. We show how these ideas may be applied to the interaction between the nanoscale-shape and the living universe and provide a conceptual framework for the study of nanoscale shape biological recognition and identity.
      281Scopus© Citations 34
  • Publication
    Current understanding of biological identity at the nanoscale and future prospects
    (Springer Nature, 2021-03) ;
    Nanoscale objects are processed by living organisms using highly evolved and sophisticated endogenous cellular networks, specifically designed to manage objects of this size. While these processes potentially allow nanostructures unique access to and control over key biological machineries, they are also highly protected by cell or host defence mechanisms at all levels. A thorough understanding of bionanoscale recognition events, including the molecules involved in the cell recognition machinery, the nature of information transferred during recognition processes and the coupled downstream cellular processing, would allow us to achieve a qualitatively novel form of biological control and advanced therapeutics. Here we discuss evolving fundamental microscopic and mechanistic understanding of biological nanoscale recognition. We consider the interface between a nanostructure and a target cell membrane, outlining the categories of nanostructure properties that are recognized, and the associated nanoscale signal transduction and cellular programming mechanisms that constitute biological recognition.
      197Scopus© Citations 88