Development of Liposomes for the Imaging of Entrapped Dyes
de Oliveira Miranda, Dyego
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Light-sensitive liposomes have been widely used for local, on demand, drug delivery for improved theranostics, and are not commonly explored for its use outside the biomedical application spectra. In this work we developed a new liposome formulation that can be used to entrap both imaging dyes and a chemotherapeutical drug for diverse applications. Chapter 1 provides a comprehensive background on the mechanisms of light-induced liposome permeabilization, explaining in depth how light interacts with liposomes via different molecular mechanisms to trigger cargo release. One of these mechanisms is called photooxidation and it is explored in Chapters 2 and 3 with the use of PoP liposomes. Chapter 2 introduces a novel PoP liposome formulation that is able to encapsulate and fast release three different cargos upon NIR laser irradiation on intratumorally injected tumors. The release cargo enabled for fluorescence and magnetic resonance imaging and chemotherapeutic treatment. Chapter 3 describes the use of solar sensitive PoP liposomes (Sol-PoP) for the entrapment of coloring food dyes and release under sunlight. This mechanism is further explored to develop a sunlight detector-like prototype to predict sunlight exposure. Finally, on Chapter 4, a modified version of IR-820 dye was chemically modified to increase solubilization in water. The new dye, named DCP-Cy, was found to form J-aggregates in the presence of salts. The aggregated form of the dye was associated with a red shift in the absorbance peak from 789 nm to 934 nm. Liposomal DCP-Cy was found to accumulate in the spleen, enabling the dye for spleen imaging with good contrast by avoiding tissue absorbance at lower wavelengths.