Radiosensitising tumour cells : Optimisations in vitro and in vivo

Abstract

One in three people in Sweden will sometime during their life be diagnosed with cancer. The most important therapies used today to treat these patients are surgery, radiation and chemotherapy. Small stapled peptides targeting the inhibition of tumour suppressor protein p53 have great potential of becoming radiosensitising drugs and increase efficacy of radiation therapy. This project aimed to test two modifications of stapled peptides PM2 and PM3 to gain further knowledge about their properties and optimise specificity and delivery of them. Radioiodination was optimised for labelling yield, oxidative stress and purification. Final product was quality tested on tumour cells to assess whether the modification affected the biological efficacy of the peptides. Results showed no reduction of efficacy. The compound was injected in tumour-bearing nude mice, resulting in tumour tissue absorption and low risk for toxicity in critical organs. Lipid bilayer disks (lipodisks) were used as a potential delivery system. The structure has previously been tested as carrier for amphiphilic peptides and shows great potential. Furthermore, it is non-toxic and biocompatible. Association of PM2 and PM3 to disks was measured with the use of fluorescence emission shift and QCM-D. Results showed that PM3 has high affinity to the disks. The study conducted here show that a drug delivery system consisting of tumour-targeting lipodisks carrying radiosensitising peptides have great potential. By adding a therapeutic radionuclide, the system can also be used for targeted radionuclide therapy