The aim of the work undertaken in this thesis was to explore the potential of synthetic peptides to enhance anti-cancer photodynamic therapy (PDT) treatment by improving targeting to tumour tissue. Chapter 1 provides an introduction to the challenges associated in the treatment of cancer, the use of peptides as therapeutics or targeting agents and the potential / limitations of current PDT. Chapter 2 discusses the methods used in each of the results chapters 3-6. The first results chapter (Chapter 3) describes how ferrocene can be used to quench ROS generation from a Rose Bengal sensetiser when both were separated by a short integrin targeting RGD containing peptide. The addition of trypsin was shown to cleave the quencher and enhance RB mediated ROS generation. In chapter 4, the sensetiser-peptide conjugate RB-C(KLAKLAK)2 was prepared, and its PDT efficacy determined in melanoma cells and melanoma tumours in mice. The results showed that the PDT treatment using RB-C(KLAKLAK)2 was significantly more efficacious than RB mediated PDT or the treatment of RB-C(KLAKLAK)2 alone. This was attributed to the peptide sensitizing the cell to ROS generation. This work was extended in Chapter 5 where the contribution of both the sensetiser and peptide to PDT mediated efficacy was studied by preparing the methylene blue – peptide analogue MB-C(KLAKLAK)2 and the shorter peptide analogue RB-CKLAKLAK. The results demonstrated that the choice of sensetiser does impact PDT efficacy but the peptide length had only a minor effect. The final results chapter, Chapter 6 describes the preparation of biotin labelled αvβ6 integrin targeting peptide A20FMDV2 and its conjugation to the surface of avidin coated liposomes. Improved uptake of the A20FMDV2 targeting liposomes was observed in αvβ6 integrin expressing BxPC-03 cells when compared to Panc-01 cells that do not over express this protein. Collectively, the results described in this thesis demonstrate the role peptides can play to enhance anti-cancer PDT efficacy or improve the delivery of drug delivery vehicles such as liposomes.
|Date of Award||Jun 2021|
|Supervisor||John Callan (Supervisor)|
- Photodynamic therapy