Biodegradable NIR-active contrast agents for photoacoustic imaging




Moaseri, Ehsan

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Biodegradable contrast agents are of great interest in biomedical imaging, in specific photoacoustic imaging, for early detection of cancer. The ideal contrast agent should exhibit sufficiently high adsorption in the near infrared (NIR) window (700–1000 nm), high photostability, and efficient conversion of heat energy to produce strong acoustic waves. Various organic and inorganic contrast agents have been studied in this thesis, including gold nanoclusters, PEG-PLGA nanocapsules loaded with copper sulfide nanoclusters, and PEG-PLGA nanocapsules loaded with ICG J-aggregates. Biodegradable NIR-active nanoclusters of 4 nm ligand-coated gold nanoparticles (NPs) were assembled in aqueous solution by controlling the interparticle interactions through varying the pH, ionic strength, and the surface ligands. These nanoclusters can fully dissociate in the physiological environment back to primary 4 nm gold NPs, which may allow for renal clearance. The spacing between NPs inside the gold nanoclusters must be less than 1 nm to achieve the required surface plasmon resonance (SPR) shift into the NIR window. Binary surface ligand coatings of thioctic acid zwitterion and citrate were used to help achieve the required interparticle spacing, allowing both for high NIR adsorption and reversible assembly/dissociation. In contrast to gold nanoclusters, close interparticle separations are not necessary to achieve strong NIR adsorption in copper sulfide nanoclusters, since the primary copper sulfide NPs already exhibit this behavior. Therefore, longer surface-passivating ligands can be employed for copper sulfide nanoparticles to effectively prevent protein opsonization in the physiological environment to facilitate successful renal clearance. Copper sulfide nanoclusters were encapsulated in PEG-PLGA nanocapsules to improve their stability and control the degradation kinetics inside the body. Finally, indocyanine green J-aggregates encapsulated in PEG-PLGA nanocapsules were synthesized as organic contrast agents made of FDA-approved constituents. These nanocapsules exhibit a sharp peak in the NIR window with favorable stability and degradation kinetics in the physiological environment. Overall, this thesis demonstrates important advances toward synthesis of biocompatible nanoscale contrast agents with control over size, stability and degradation kinetics


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