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Philip JT Reardon,1,* Maryam Parhizkar,2,* Anthony H Harker,3 Richard J Browning,4 Vessela Vassileva,5 Eleanor Stride,4 R Barbara Pedley,5 Mohan Edirisinghe,2 Jonathan C Knowles1 1Division of Biomaterials and Tissue Engineering, UCL Eastman Dental Institute, 2Department of Mechanical Engineering, 3Department of Physics & Astronomy, University College London, London, 4Institute of Biomedical Engineering, Department of Engineering Science, University of Oxford, Oxford, 5Department of Oncology, UCL Cancer Institute, University College London, London, UK *These authors contributed equally to this work Abstract: Increasing the clinical efficacy of toxic chemotherapy drugs such as cisplatin (CDDP), via targeted drug delivery, is a key area of research in cancer treatment. In this study, CDDP-loaded poly(lactic-co-glycolic acid) (PLGA) polymeric nanoparticles (NPs) were successfully prepared using electrohydrodynamic atomization (EHDA). The configuration was varied to control the distribution of CDDP within the particles, and high encapsulation efficiency (>70%) of the drug was achieved. NPs were produced with either a core–shell (CS) or a matrix (uniform) structure. It was shown that CS NPs had the most sustained release of the 2 formulations, demonstrating a slower linear release post initial “burst” and longer duration. The role of particle architecture on the rate of drug release in vitro was confirmed by fitting the experimental data with various kinetic models. This indicated that the release process was a simple diffusion mechanism. The CS NPs were effectively internalized into the endolysosomal compartments of cancer cells and demonstrated an increased cytotoxic efficacy (concentration of a drug that gives half maximal response [EC50] reaching 6.2 µM) compared to free drug (EC50 =9 µM) and uniform CDDP-distributed NPs (EC50 =7.6 µM) in vitro. Thus, these experiments indicate that engineering the structure of PLGA NPs can be exploited to control both the dosage and the release characteristics for improved clinical chemotherapy treatment. Keywords: cisplatin, drug delivery, cancer chemotherapy, polymer, poly(lactic-co-glycolic acid), nanoparticles, electrohydrodynamic atomization, controlled release

The phytohormone auxin plays a vital role in almost every aspect of plant growth and development. Expression of auxin-responsive genes is controlled by a family of Auxin Response Factor (ARF) transcription factor family. This study examined the function and expression pattern of a gene encoding Auxin Response Factor B3 from Medicago truncatula (MtARF-B3) after its heterologous expression in the model plant Arabidopsis thaliana. Stable transgenic plants with ARF-B3 overexpres-sion, downregulation and transcriptional reporters were constructed. Transcriptional and histochemical assays revealed a stable MtARF-B3 expression in various stages of somatic embryogenesis and during the postembryonic development of A. thaliana. Morphological analysis and morphometric measurements confirmed the important role of MtARF-B3 in general plant growth and development, root growth and seed production. [ABSTRACT FROM AUTHOR]

Phenotypic evaluation of epigenetic mutants is mainly based on the analysis of plant growth and morphological features. However, there are cellular level changes that are not visible to the naked eye and require analysis with higher resolution techniques. In this study, we carried out a phenotypic characterisation of several Arabidopsis thaliana hypomethylation mutants by quantitative image analysis combined with flow cytometry. This phenotyping approach permitted identification of abnormalities at the cellular level in mutants with wild-type morphology at the organ level. Morphometry of adaxial leaf epidermis revealed variations in the size and number of pavement cells, and the density and distribution of stomata in the analysed second rosette leaves from the mutants studied. A direct correlation between DNA ploidy status and leaf pavement cell size in wild type and mutant leaves was observed. Recognition of hidden phenotypic variations could facilitate the identification of key genetic loci underlying the phenotypes caused by modifications of DNA methylation. Thus, this study outlines an easy and fast phenotyping strategy that can be used as a reliable tool for characterisation of epigenetic mutants at the cellular level. [ABSTRACT FROM AUTHOR]