Magnetic nanobeads decorated by thermo-responsive PNIPAM shell as medical platforms for the efficient delivery of doxorubicin to tumour cells

Medical nanoplatforms based on clusters of superparamagnetic nanoparticles decorated with a PNIPAM thermo-responsive shell have been synthesized and used as drug carriers for doxorubicin (DOXO), a common chemotherapeutic agent. The nanosystem here developed has a total diameter below 200 nm and exploits the temperature responsive behaviour of the PNIPAM polymeric shell for the controlled loading and release of DOXO. The system has been tested in vitro on tumour cells and it clearly demonstrates the effectiveness of drug polymer encapsulation and time-dependent cell death induced by the doxorubicin release. Comparative cellular studies of the DOXO loaded nanoplatform in the presence or absence of an external magnet (0.3 T) showed the synergic effect of accumulation and enhanced toxicity of the system, when magnetically guided, resulting in the enhanced efficacy of the system

High‐Throughput Miniaturized Screening of Nanoparticle Formation via Inkjet Printing

This is the peer reviewed version of the following article:Ioanna D. Styliari, et al, ‘High‐Throughput Miniaturized Screening of Nanoparticle Formation via Inkjet Printing’, Macromolecular Materials and Engineering, (2018), which has been published in final form at https://doi.org/10.1002/mame.201800146. Under embargo until 27 May 2019. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.The self‐assembly of specific polymers into well‐defined nanoparticles (NPs) is of great interest to the pharmaceutical industry as the resultant materials can act as drug delivery vehicles. In this work, a high‐throughput method to screen the ability of polymers to self‐assemble into NPs using a picoliter inkjet printer is presented. By dispensing polymer solutions in dimethyl sulfoxide (DMSO) from the printer into the wells of a 96‐well plate, containing water as an antisolvent, 50 suspensions are screened for nanoparticle formation rapidly using only nanoliters to microliters. A variety of polymer classes are used and in situ characterization of the submicroliter nanosuspensions shows that the particle size distributions match those of nanoparticles made from bulk suspensions. Dispensing organic polymer solutions into well plates via the printer is thus shown to be a reproducible and fast method for screening nanoparticle formation which uses two to three orders of magnitude less material than conventional techniques. Finally, a pilot study for a high‐throughput pipeline of nanoparticle production, physical property characterization, and cytocompatibility demonstrates the feasibility of the printing approach for screening of nanodrug delivery formulations. Nanoparticles are produced in the well plates, characterized for size and evaluated for effects on metabolic activity of lung cancer cells.Peer reviewe

Perforated red blood cells enable compressible and injectable hydrogels as therapeutic vehicles

Hydrogels engineered for medical use within the human body need to be delivered in a minimally invasive fashion without altering their biochemical and mechanical properties to maximize their therapeutic outcomes. In this regard, key strategies applied for creating such medical hydrogels include formulating precursor solutions that can be crosslinked in situ with physical or chemical cues following their delivery or forming macroporous hydrogels at sub-zero temperatures via cryogelation prior to their delivery. Here, we present a new class of injectable composite materials with shape recovery ability. The shape recovery is derived from the physical properties of red blood cells (RBCs) that are first modified via hypotonic swelling and then integrated into the hydrogel scaffolds before polymerization. The RBCs' hypotonic swelling induces the formation of nanometer-sized pores on their cell membranes, which enable fast liquid release under compression. The resulting biocomposite hydrogel scaffolds display high deformability and shape-recovery ability. The scaffolds can repeatedly compress up to ~87% of their original volumes during injection and subsequent retraction through syringe needles of different sizes; this cycle of injection and retraction can be repeated up to ten times without causing any substantial mechanical damage to the scaffolds. Our biocomposite material system and fabrication approach for injectable materials will be foundational for the minimally invasive delivery of drug-loaded scaffolds, tissue-engineered constructs, and personalized medical platforms that could be administered to the human body with conventional needle-syringe systems

A comprehensive evaluation of the activity and selectivity profile of ligands for RGD-binding integrins

Integrins, a diverse class of heterodimeric cell surface receptors, are key regulators of cell structure and behaviour, affecting cell morphology, proliferation, survival and differentiation. Consequently, mutations in specific integrins, or their deregulated expression, are associated with a variety of diseases. In the last decades, many integrin-specific ligands have been developed and used for modulation of integrin function in medical as well as biophysical studies. The IC50-values reported for these ligands strongly vary and are measured using different cell-based and cell-free systems. A systematic comparison of these values is of high importance for selecting the optimal ligands for given applications. In this study, we evaluate a wide range of ligands for their binding affinity towards the RGD-binding integrins avß3, avß5, avß6, avß8, a5ß1, aIIbß3, using homogenous ELISA-like solid phase binding assay.Postprint (published version

Will Jargon Use Increase or Decrease a Doctor\u27s Credibility? Exploring the Moderating Effects of eHealth Literacy and Question Type

Doctors are accustomed to using jargon to communicate in online medical communities, but is it actually effective? In this article, we propose two diametrically opposed mechanisms of jargon use that affect patients\u27 confidence in providers of online medical consultation services: The use of jargon affects competence-based confidence positively, but negatively on benevolence- and integrity-based trust. We take into account the moderating effects of eHealth literacy and question type to better comprehend the circumstances in which jargon use is at play. To test our conceptual model, we conduct a scenario experiment and then use a survey method to collect 203 valid questionnaires. Finally, we discuss our findings, their implications for theory and practise, and the study\u27s limitations

Development of advanced 3D medical analysis tools for clinical training, diagnosis and treatment

This thesis was submitted for the degree of Doctor of Philosophy and awarded by Brunel University.The objective of this PhD research was the development of novel 3D interactive medical platforms for medical image analysis, simulation and visualisation, with a focus on oncology images to support clinicians in managing the increasing amount of data provided by several medical image modalities. DoctorEye and Automatic Tumour Detector platforms were developed through constant interaction and feedback from expert clinicians, integrating a number of innovations in algorithms and methods, concerning image handling, segmentation, annotation, visualisation and plug-in technologies. DoctorEye is already being used in a related tumour modelling EC project (ContraCancrum) and offers several robust algorithms and tools for fast annotation, 3D visualisation and measurements to assist the clinician in better understanding the pathology of the brain area and define the treatment. It is free to use upon request and offers a user friendly environment for clinicians as it simplifies the implementation of complex algorithms and methods. It integrates a sophisticated, simple-to-use plug-in technology allowing researchers to add algorithms and methods (e.g. tumour growth and simulation algorithms for improving therapy planning) and interactively check the results. Apart from diagnostic and research purposes, it supports clinical training as it allows an expert clinician to evaluate a clinical delineation by different clinical users. The Automatic Tumour Detector focuses on abdominal images, which are more complex than those of the brain. It supports full automatic 3D detection of kidney pathology in real-time as well as 3D advanced visualisation and measurements. This is achieved through an innovative method implementing Templates. They contain rules and parameters for the Automatic Recognition Framework defined interactively by engineers based on clinicians’ 3D Golden Standard models. The Templates enable the automatic detection of kidneys and their possible abnormalities (tumours, stones and cysts). The system also supports the transmission of these Templates to another expert for a second opinion. Future versions of the proposed platforms could integrate even more sophisticated algorithms and tools and offer fully computer-aided identification of a variety of other organs and their dysfunctions