Theranostic porphyrin conjugates for the combined treatment and diagnosis of cancer

Yap, Steven Yong-Yi

Abstract

The development of theranostic agents capable of the combined treatment of diagnosis of disease has seen a growing interest within the research community. The combination of diagnostic and treatment modality onto a single construct will allow the careful monitoring of the biodistribution of drug molecules, allowing optimisation of treatment, paving a way towards personalised medicines.

Photodynamic therapy (PDT) is a promising treatment technique for cancer. It is minimally invasive and shows little or no toxicity which proves advantageous over traditional anti-cancer techniques. It involves the administration of a non-toxic drug known as photosensitiser and the irradiation with visible light to activate the photosensitisers. The activated photosensitiser will generate reactive oxygen species that can deal oxidative damage to surrounding tissues, culminating in cell death. Hence, the selective accumulation of the photosensitiser into diseased tissues is of utmost importance for photodynamic therapy.

This make photosensitisers for photodynamic therapy an ideal candidate to be combined with a diagnostic modality, allowing the monitoring of accumulation of photosensitisers, improving treatment outcomes by irradiation when photosensitiser levels are maximal. Therapeutic abilities of porphyrin as a photosensitiser are undisputed, their ease of synthesis and functionalisation made them the photosensitiser of choice to combine with a diagnostic modality. Magnetic resonance imaging (MRI), positron emission tomography (PET), and single photon emission tomography (SPECT) are of particular interest as they are routinely used in clinics and allow the imaging of the distribution of the imaging agent.

In this thesis, molecular- and nano-theranostic agents were investigated to combine PDT with MRI contrast agent, PET radioisotope, or SPECT radioisotope. A brief introduction of these treatment and diagnostic techniques along with the current advances in theranostic is given in chapter 1. The bioconjugation of cowpea mosaic virus, a biological nanoplatform, with porphyrin is described in chapter 2. Synthesis of polyacrylamide nanoparticles for the encapsulation and functionalisation of porphyrin and MRI contrast molecules is described in chapter 3. Molecular-theranostic agents is described in chapter 4 and chapter 5; chapter 4 describes a PDT/PET theranostic agent and chapter 5 describe two molecular theranostics. prostate-targeted and non-targeted PDT/SPECT theranostic agents.

Successful synthesis and evaluation of these theranostic agents led to the in vitro and in vivo analysis to evaluate their efficacy in PDT treatment and MR/PET/SPECT imaging.

Citation

Yap, S. Y. (2019). Theranostic porphyrin conjugates for the combined treatment and diagnosis of cancer. (Thesis). University of Hull. Retrieved from https://hull-repository.worktribe.com/output/4221753

• Thesis Type: Thesis
• Deposit Date: Aug 6, 2019
• Publicly Available Date: Feb 23, 2023
• Keywords: Chemistry
• Public URL: https://hull-repository.worktribe.com/output/4221753
• Additional Information: Department of Chemistry, The University of Hull
• Award Date: Apr 1, 2019