Mapping the Intracellular Temperature Dynamics with Organelle-Targeted Upconversion Nanoparticles

Di, Xiangjun

Mapping the Intracellular Temperature Dynamics with Organelle-Targeted Upconversion Nanoparticles

Di, Xiangjun

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Publication Type:: Thesis
Issue Date:: 2022

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Field	Value	Language
dc.contributor.author	Di, Xiangjun
dc.date.accessioned	2023-03-30T00:45:47Z
dc.date.available	2023-03-30T00:45:47Z
dc.date.issued	2022
dc.identifier.uri	http://hdl.handle.net/10453/168819
dc.description	University of Technology Sydney. Faculty of Science.	en_US.UTF-8
dc.description.abstract	Temperature plays a key role in regulating intracellular activities. Accurate measurements of temperature inside living cells at the nanoscale can tell if the cells are under their healthy physiological status or in dysfunctional diseases. As the energy factory and metabolism center, mitochondria constantly release heat during ATP production, which greatly impacts the intracellular organelles’ temperature. A direct visualization platform with probes that can sense the in situ temperature dynamics of mitochondria, and map the temperature-related interactions among intercellular organelles, will facilitate our understanding of mitochondria-related diseases towards better therapy. Upconversion nanoparticles (UCNPs), being excited by near-infrared (NIR) light to generate visible light, have been widely applied in the fields of single-molecule bioassays, super-resolution microscopy, and recently non-contact thermometers, due to their unique optical properties, including their exceptional photo-stability against photo-bleaching or photo-blinking, tunable multi-wavelength emissions for multiplexing assays, anti-Stokes’ emissions to suppress autofluorescence background, near infrared excitation and emissions allowing deep-tissue penetration depth, and most importantly, temperature-dependent ratiometric luminescence for thermometry application. However, the chemical stability of hydrophilic UCNPs has limited their developments in biomedical applications. To obtain the hydrophilic UCNPs (NaYF4: 20%Yb3+, 2%Er3+) with excellent stability and dispersibility in aqueous physiological buffers, five different functionalization strategies have been systematically evaluated (chapter 2). To study the temperature dynamics of mitochondria, I developed a mitochondria-targeting UCNPs-based thermometer with a sensing sensitivity of 3.2% K-1 to monitor the temperature variations through the chemical stimulations. The cells displayed distinct response time and temperature dynamic profiles (chapter 3). To further study the interaction between lysosomes and mitochondria, I updated the design of UCNPs-based thermometer by optimizing the surface functionalization of UCNPs, which resulted in an enhanced reliability with the relative temperature sensing sensitivity of 2.7% K-1 and temperature uncertainty of 0.8 K in HeLa cells. The new probes can cascade target lysosomes and mitochondria, respectively (chapter 4). Chapter 5 concludes this thesis by providing a thermometry platform to study the temperature dynamics of mitochondria and organelles’ functional interactions under the physiological or pathological status. Combined with other state-of-the-art technologies, such as sequential labelling of mtDNA, super-resolution imaging, UCNPs-based thermometer will become a powerful multimodal probe for imaging, sensing, and therapy.	en_US.UTF-8
dc.format	Thesis (PhD)
dc.language.iso	en_US	en_US.UTF-8
dc.relation	https://opus.lib.uts.edu.au/bitstream/10453/168819/2/02whole.pdf
dc.rights	info:eu-repo/semantics/openAccess
dc.rights	The author owns the copyright in this thesis including all reproduction and reuse rights for the work. The work may not be altered without the permission of the copyright owner. Attribution is essential when quoting or paraphrasing from this thesis.
dc.rights	© 2022 Xiangjun Di
dc.rights	au.edu.uts.lib/ppc
dc.title	Mapping the Intracellular Temperature Dynamics with Organelle-Targeted Upconversion Nanoparticles	en_US.UTF-8
dc.type	Thesis
utslib.copyright.status	open_access	*

Abstract:

Temperature plays a key role in regulating intracellular activities. Accurate measurements of temperature inside living cells at the nanoscale can tell if the cells are under their healthy physiological status or in dysfunctional diseases. As the energy factory and metabolism center, mitochondria constantly release heat during ATP production, which greatly impacts the intracellular organelles’ temperature. A direct visualization platform with probes that can sense the in situ temperature dynamics of mitochondria, and map the temperature-related interactions among intercellular organelles, will facilitate our understanding of mitochondria-related diseases towards better therapy. Upconversion nanoparticles (UCNPs), being excited by near-infrared (NIR) light to generate visible light, have been widely applied in the fields of single-molecule bioassays, super-resolution microscopy, and recently non-contact thermometers, due to their unique optical properties, including their exceptional photo-stability against photo-bleaching or photo-blinking, tunable multi-wavelength emissions for multiplexing assays, anti-Stokes’ emissions to suppress autofluorescence background, near infrared excitation and emissions allowing deep-tissue penetration depth, and most importantly, temperature-dependent ratiometric luminescence for thermometry application. However, the chemical stability of hydrophilic UCNPs has limited their developments in biomedical applications. To obtain the hydrophilic UCNPs (NaYF4: 20%Yb3+, 2%Er3+) with excellent stability and dispersibility in aqueous physiological buffers, five different functionalization strategies have been systematically evaluated (chapter 2). To study the temperature dynamics of mitochondria, I developed a mitochondria-targeting UCNPs-based thermometer with a sensing sensitivity of 3.2% K-1 to monitor the temperature variations through the chemical stimulations. The cells displayed distinct response time and temperature dynamic profiles (chapter 3). To further study the interaction between lysosomes and mitochondria, I updated the design of UCNPs-based thermometer by optimizing the surface functionalization of UCNPs, which resulted in an enhanced reliability with the relative temperature sensing sensitivity of 2.7% K-1 and temperature uncertainty of 0.8 K in HeLa cells. The new probes can cascade target lysosomes and mitochondria, respectively (chapter 4). Chapter 5 concludes this thesis by providing a thermometry platform to study the temperature dynamics of mitochondria and organelles’ functional interactions under the physiological or pathological status. Combined with other state-of-the-art technologies, such as sequential labelling of mtDNA, super-resolution imaging, UCNPs-based thermometer will become a powerful multimodal probe for imaging, sensing, and therapy.

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