Ratier, A (2021) Fluorescent nanosensors for the monitoring of different intracellular reactive oxygen species (ROS). Doctoral thesis, Liverpool John Moores University.

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Abstract

Reactive oxygen species (ROS) play important roles for the regulation of normal functions such as proliferation, differentiation, migration and cell death. At low doses they participate in the redox balance, but an excess of these species leads to damage to proteins, lipids or DNA. ROS are involved in the onset and progression of several degenerative diseases (e.g., cancer, neurological disorder, etc). Cancer cells are highly susceptible to ROS-mediated damage and several chemotherapy agents achieve cytotoxicity by inducing oxidative stress. Sensing the variations of different intracellular ROS is crucial for real time assessments of anticancer treatment efficiency. Yet, no sensor currently allows simultaneous and independent monitoring of different ROS live cells. Indeed, existing sensors monitor either the total levels of ROS or the levels of single species (i.e., sensors such as diphenylanthracene, peroxy yellow, anthrafluorescein, etc.). The need to optimise and personalise treatment regimens and for unravelling the mechanisms underpinning ROS-induced cell death requires the introduction of a new set of tools able to provide a real-time report of intracellular ROS levels in response to a given intervention. In this project we developed new fluorescent nanosensors able to respond to different ROS. This was achieved through the synthesis of three conjugatable molecular probes able to respond to individual ROS, namely; an anthrafluorescein-based probe for superoxide anion, a dimethylanthracene-based probe for singlet oxygen and a fluorescein-based probe for hydrogen peroxide. The new probes were grafted onto poly(lactic-co-glycolic acid) (PLGA) and formulated as nanoparticles containing either conjugated or encapsulated sensors. We characterised the fluorescent response of the probes, conjugates and nanospecies in the presence of the target ROS analytes. Lastly, we demonstrated the ability of the nanosensors to enter cells and their potential of to be used as intracellular ROS sensors.

Item Type:	Thesis (Doctoral)
Uncontrolled Keywords:	Reactive Oxygen species; Fluorescent sensors; Nanosensors
Subjects:	Q Science > QD Chemistry Q Science > QH Natural history > QH301 Biology R Medicine > RM Therapeutics. Pharmacology
Divisions:	Pharmacy & Biomolecular Sciences
Date Deposited:	26 Jul 2021 08:41
Last Modified:	18 Oct 2022 14:03
DOI or ID number:	10.24377/LJMU.t.00015311
Supervisors:	Giuntini, F, Hutcheon, G and Casey, D
URI:	https://researchonline.ljmu.ac.uk/id/eprint/15311

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