Development and Characterization of Laser-Activated Perfluorocarbon Nanodroplets as Theranostic Agents
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Zhao, Andrew Xin
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Abstract
Perfluorocarbon nanodroplets have been primarily explored as a next-generation contrast agent for ultrasound imaging, providing significant advantages over microbubbles in terms of circulation time and size, which enables them to extravasate and reach extravascular targets. Furthermore, these nanoparticles can be triggered acoustically or optically to form microbubbles in situ. While acoustic droplet vaporization has been extensively studied, optical droplet vaporization holds promise as an alternative approach. It allows for the incorporation of photoacoustic imaging to visualize vaporization and can be used to vaporize high boiling point cores safely and repeatedly.
In this dissertation, optically triggerable PFCnDs are further developed as theranostic agents. The formulation of PFCnDs is varied to gain a better understanding of optical droplet vaporization and to improve the particle’s imaging performance. The therapeutic applications are explored from two angles: impact of the vaporization and release of encapsulated drugs.
In CHAPTER 3, the performance of optically activatable PFCnDs are examined, considering factors such as shell and core materials, laser parameters, and environmental conditions. Novel longitudinal behaviors of the nanodroplets are described that can allow for more effective detection in the body and provide insights into how the formulation impacts the vaporization threshold. These findings provide a better foundation for advancing our understanding of optical droplet vaporization.
In CHAPTER 4, the effect of lasing the nanodroplets in close proximity to the cells are explored. The nanodroplets exhibit a similar behavior to sonoporation, creating pores in the cell membrane that enable extracellular molecules to enter the cytoplasm. The different conditions required to optimize this behavior and viability are explored in detail such as the concentration of the PFCnDs, laser fluence, pulse number, and size of the molecules that can enter.
In CHAPTER 5, double emulsion perfluorohexane nanodroplets (dePFHnDs) are developed by modifying the formulation of PFCnDs to encapsulate hydrophilic molecules. This new class of PFCnDs can be tracked photoacoustically and triggered to release drugs acoustically. Photoacoustic monitoring can be performed without releasing the encapsulated drug, allowing for estimations of release based upon signal reduction.
In summary, this dissertation represents an advancement of PFCnDs as a theranostic agent. Our understanding of optical droplet vaporization is improved, allowing for better diagnostic applications, and expand the therapeutic capabilities of these nanodroplets in drug delivery. These developments contribute to making PFCnDs a more effective drug delivery agent.
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Date
2023-11-28
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Dissertation