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Title: Nanomaterials for biosensing and cancer therapy
Author: Jumeaux, Coline Barbara
ISNI:       0000 0004 7657 0499
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2017
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The unique features exhibited by nanomaterials endow them with great potential for applications interfacing with biological systems, and self-assembly enables to gain control over their architecture for fine-tuning of their properties and performances to achieve a highly specific response. High specificity is a key requirement for both biosensing and cancer therapy. This thesis explores the use of self-assembled nanomaterials for the development of new biosensing mechanisms and the design of stimuli-responsive drug delivery platforms for cancer therapy. MicroRNAs (miRNAs) present unique detection challenges, arising from their low abundance in clinical samples, short size, and high sequence homology. Here, DNA-mediated liposome fusion is used for highly specific detection of a clinically-relevant miRNA, initially using a standard laboratory microplate reader. Further, 2-color nanoparticle tracking microscopy is employed to directly follow fusion events occurring in liquid suspension, and a new analytical approach is developed to convert these observations into dose-response curves for increasing the sensitivity of the detection. In parallel, another strategy for increasing the assay sensitivity is explored, involving covalent binding of FRET pair dyes inside lipid bilayers. Further, cancer treatment at the nanoscale allows circumventing the limitations associated with conventional chemotherapy, by providing ways to enhance the treatment's specificity, increasing the aqueous solubility of anticancer molecules, improving their biodistribution, reversing multidrug resistance, and offering the possibility for personalized therapy. The nanovector employed in this project is the quantum rattle (QR), and is made of a mesoporous silica shell encapsulating gold nanoparticles and gold nanoclusters. In order to address QR towards a systemically administered multifunctional system for cancer therapy, it is engineered into a triggered release drug delivery system. A layer-by-layer type construct is designed using a thermoresponsive polymer, which provides a coating for QR, only allowing drug release after application of a trigger, here laser-induced gold-mediated hyperthermia.
Supervisor: Stevens, Molly ; Porter, Alexandra Sponsor: Rosetrees Trust
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral