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Optimising polymersomes for imaging tumour and its environment

Joseph, Adrian (2014) Optimising polymersomes for imaging tumour and its environment. PhD thesis, University of Sheffield.

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Abstract

Polymersomes are nano-meter sized vesicles made by the self assembly of amphiphilic co-polymers in water. This work presents the development of polymersomes as a tool for high resolution in vivo optical imaging. High resolution Intra Vital Microscopy (IVM) was made possible by the use of the Window Chamber (WC), a surgical procedure which allows observation of living tissues through an optically transparent glass replacing a section of skin. WC can be used to observe tumour growth and tumour vasculature development (angiogenesis). High resolution imaging of angiogenesis in vivo with polymersomes can give an useful insight in mechanism of angiogenesis, tumour response to anti-angiogenic therapy and the rationale behind the design of polymersomes for speci�c tumour targeting in therapy. In this work we optimised a number of techniques and tools to characterise the interactions of two diff�erent polymersome formulation with three cell types relevant to the tumour microenvironment: tumour cells Mouse Fibrosarcoma Cell (MFC), endothelial cells Small Vessel Endothelial Cells (SVECs) and perivascularlike cells 10T1/2. The techniques used included Reverse Phase-High Pressure Liquid Chromatography (RP-HPLC), Fluorescence Activated Cell Sorting (FACS) and optical imaging. Furthermore, a flow bio-incubator was developed to study the effect of physiologically relevant flow rates on cellular polymersome uptake. Finally, formulations were tested in vivo to assess suitability for optical imaging and polymersomes distribution in tumour vasculature and stroma. Specific image analysis tool were developed to assist the analysis. The results demonstrated that polymersomes can be used for optical imaging in vivo using a WC. The in vitro techniques developed allowed us to quantify the interactions between polymersomes and cells, and the information gained can be translated in vivo to help predict the polymersomes distribution in tumour. Taken together, the methods and results presented here provide a set of tools based on image analysis that allow rational design of polymersomes for in vivo application.

Item Type: Thesis (PhD)
Academic Units: The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > Medicine (Sheffield)
Identification Number/EthosID: uk.bl.ethos.631453
Depositing User: Dr Adrian Joseph
Date Deposited: 05 Dec 2014 14:22
Last Modified: 03 Oct 2016 11:18
URI: http://etheses.whiterose.ac.uk/id/eprint/7458

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