Photodynamic therapy (PDT) has been used as a clinical treatment since the early 1990s and utilizes a photosensitising drug (PS), molecular oxygen and light of a specific wavelength, (usually visible light below 700nm) to generate singlet oxygen and other reactive oxygen species which are highly cytotoxic. Originally used as a treatment for superficial skin cancer it is now emerging as a treatment for other forms of cancer such as head, neck, lung and prostate cancers. There are however, several limitations which have prevented PDT obtaining wide spread clinical use. For example currently approved PS drugs absorb light in the visible region limiting tissue depth penetration to a few mm rendering the treatment unsuitable for deep seated tumours. Secondly, PS molecules also tend to be hydrophobic and can aggregate in aqueous solutions, leading to a reduction in singlet oxygen production. The focus of this PhD seeks to take advantage of the photophysical properties of conventional cadmium selenide quantum dots (QDs) (chapter 3) and the relatively new carbon based nano material known as carbon quantum dots (CQDs) (chapter 4), to address some of the difficulties currently faced with the use of conventional PS drugs in PDT. This strategy shall involve the synthesis, in vitro and in vivo evaluation of suitable nano-particlePS conjugates. In addition to the synthesis of conjugates for PDT implications, microbubblesensitiser conjugates were also developed for use in sonodynamic therapy (SDT). SDT refers to the ultrasound dependent cytotoxic effect of certain compounds (sonosensitisers). Ultrasound having far superior tissue dept penetration than light, overcoming the major limitation of poor tissue depth penetration observed in PDT. However there are still some undesirable characteristics associated with SDT. The accumulation of sonosensitisers in healthy tissue has been one such drawback, as sonosentisers (SS) are generally also PS this can lead to photosensitivity of the skin. In order to achieve a greater degree of selectivity the use of microbubble-SS conjugates was investigated (chapter 5). Lipid based microbubbles (MBs) are currently approved for use as contrast agents in diagnostic ultrasound applications and have also been investigated as potential drug / gene delivery vehicles. In chapter 5 Rose Bengal, a well known SS, was covalently attached to the surface of a lipid coated MB. The overall objective of this strategy was to investigate the potential of this MB-SS conjugate as a therapeutic for highly targeted, minimally invasive treatment of deep seated tumours.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:692835 |
| Date | January 2013 |
| Creators | Fowley, Colin Paul |
| Publisher | Ulster University |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
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