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Title: Targeted approaches for the treatment of solid cancerous tumours
Author: Atchison, Jordan Daniel
ISNI:       0000 0004 7229 0254
Awarding Body: Ulster University
Current Institution: Ulster University
Date of Award: 2017
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There is an urgent need for site-specific drug delivery systems or new treatment options with improved targeting capability. This thesis investigated new methods for targeted delivery of sensitisers and drugs to solid tumours. Chapter 3 details the development of a pH responsive sensitiser to exploit the lower pH present in cancer tissue when compared to non-cancer tissue as a targeting method. Modifying pH enabled control over ROS generation and cellular toxicity which was confirmed both in vitro and in vivo. In Chapter 4, an amphiphilic polymer was used to encapsulate the photosensitiser hypericin and enable its dispersion in aqueous media. Targeting was increased by attaching folic acid to the polymeric micelle and its effectiveness compared to a non-labelled analogue was determined through studying the PDT mediated toxicity in folate receptor positive (FR+ve) and folate receptor negative (FR-ve) cell lines. A significantly improved efficacy was observed in the FR+ve cell line for the labelled complex while no significant difference was observed in the FR-ve cell line. Chapter 5 describes the synthesis of a near infrared (NIR) absorbing sensitiser containing multiple iodine atoms, to overcome the issue of light penetration while also limiting the problem associated with activation by ambient light. The efficacy was determined in two pancreatic cancer cell lines and an in vivo murine model of the disease. A significant NIR activated PDT mediated reduction in cell viability was found compared to the non-iodinated analogue. The di-iodinated derivative also produced significant PDT mediated reductions in vivo. In Chapter 6 an azide functionalised doxorubicin prodrug was prepared and encapsulated in a polymeric micelle. When delivered to HeLa cells along with a similar micelle containing PPh3 in the core, a significant reduction in cell viability was observed, as the prodrug is effectively converted to the active doxorubicin via an intracellular Staudinger reaction.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available