Now showing 1 - 5 of 5
  • Publication
    Spatiotemporally Resolved Heat Dissipation in 3D Patterned Magnetically Responsive Hydrogels
    Multifunctional nanocomposites that exhibit well-defined physical properties and encode spatiotemporally controlled responses are emerging as components for advanced responsive systems, for example, in soft robotics or drug delivery. Here an example of such a system, based on simple magnetic hydrogels composed of iron oxide magnetic nanoflowers and Pluronic F127 that generates heat upon alternating magnetic field irradiation is described. Rules for heat-induction in bulk hydrogels and the heat-dependence on particle concentration, gel volume, and gel exposed surface area are established, and the dependence on external environmental conditions in “closed” as compared to “open” (cell culture) system, with controllable heat jumps, of ∆T 0–12°C, achieved within ≤10 min and maintained described. Furthermore the use of extrusion-based 3D printing for manipulating the spatial distribution of heat in well-defined printed features with spatial resolution <150 µm, sufficiently fine to be of relevance to tissue engineering, is presented. Finally, localized heat induction in printed magnetic hydrogels is demonstrated through spatiotemporally-controlled release of molecules (in this case the dye methylene blue). The study establishes hitherto unobserved control over combined spatial and temporal induction of heat, the applications of which in developing responsive scaffold remodeling and cargo release for applications in regenerative medicine are discussed.
      443Scopus© Citations 20
  • 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
    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
    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.
  • Publication
    Graphene oxide modulates inter-particle interactions in 3D printable soft nanocomposite hydrogels restoring magnetic hyperthermia responses
    Hydrogels loaded with magnetic iron oxide nanoparticles that can be patterned and which controllably induce hyperthermic responses on AC-field stimulation are of interest as functional components of next-generation biomaterials. Formation of nanocomposite hydrogels is known to eliminate any Brownian contribution to hyperthermic response (reducing stimulated heating) while the Néel contribution can also be suppressed by inter-particle dipolar interactions arising from aggregation induced before or during gelation. We describe the ability of graphene oxide (GO) flakes to restore the hyperthermic efficiency of soft printable hydrogels formed using Pluronics F127 and PEGylated magnetic nanoflowers. Here, by varying the amount of GO in mixed nanocomposite suspensions and gels, we demonstrate GO-content dependent recovery of hyperthemic response in gels. This is due to progressively reduced inter-nanoflower interactions mediated by GO, which largely restore the dispersed-state Néel contribution to heating. We suggest that preferential association of GO with the hydrophobic F127 blocks increases the preponderance of cohesive interactions between the hydrophilic blocks and the PEGylated nanoflowers, promoting dispersion of the latter. Finally we demonstrate extrusion-based 3D printing with excellent print fidelity of the magnetically-responsive nanocomposites, for which the inclusion of GO provides significant improvement in the spatially-localized open-coil heating response, rendering the prints viable components for future cell stimulation and delivery applications.
      475Scopus© Citations 10