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In vitro photodynamic therapy screening with carbon dot-protoporphyrin IX conjugates

Aguilar Cosme, Jose Ricardo (2020) In vitro photodynamic therapy screening with carbon dot-protoporphyrin IX conjugates. PhD thesis, University of Sheffield.

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Abstract

Cancer is a leading cause of death, being responsible for over 9.6 million deaths worldwide in 2018. Photodynamic therapy (PDT) is an alternative cancer treatment with FDA approval. It is based on the use of photosensitisers (PS) such as protoporphyrin IX (PpIX), which are activated through light and produce singlet oxygen when irradiated, leading to tumour ablation. Highly controlled light dosimetry and rapid drug uptake maximizes the PDT effect while protecting surrounding tissue from damage. However, it is limited by inefficient drug accumulation in target tissue, light scattering, variable oxygen gradients, and high toxicity. Carbon dots (CDs) are carbon-based fluorescent nanoparticles that have gained attention due to their interesting photophysical properties, low toxicity, tuneable surface functionality and adaptable synthesis making them ideal candidates for drug delivery, bioimaging, and theragnostics applications. CDs have been previously used for PDT as PS carriers and have shown great success in improving treatment efficiency. However, to date, no comparison between conjugates with different drug loading strategies has been made to determine the best-performing methodology. This research aimed to produce PpIX-loaded conjugates capable of an enhanced PDT effect. Conjugates should be water-dispersible and produce singlet oxygen, demonstrating enhanced photoluminescence, fast intracellular uptake, low dark toxicity, and high light toxicity. In this work, carbon dot (CD) and protoporphyrin IX (PpIX) conjugates were fabricated using microwave-assisted pyrolysis. CDs were shown to be highly useful and effective carriers for PpIX, demonstrating an enhanced PDT effect through advantageous intracellular localization and decreased cytotoxicity. The use of cancer spheroids and morphometric parameter acquisition demonstrated how multiple treatment parameters can be simultaneously screened to determine optimum ranges for further experiments.

Item Type: Thesis (PhD)
Academic Units: The University of Sheffield > Faculty of Engineering (Sheffield) > Materials Science and Engineering (Sheffield)
Depositing User: Dr Jose Ricardo Aguilar Cosme
Date Deposited: 14 May 2020 16:23
Last Modified: 14 May 2020 16:23
URI: http://etheses.whiterose.ac.uk/id/eprint/26777

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