Fundamentals of Porphyrin-lipid J-aggregation in Nanomedicine

Nanomedicine takes advantage of new, medically useful properties that arise from nanoscale control of material composition and structure. This thesis investigates a nanoscale photophysical phenomenon called J-aggregation within the context of porphyrin-lipid nanomedicine. Porphyrins are endogenous chromophores medically used as photosensitizers and optical imaging agents. Conjugating porphyrins to lipids enables their self-assembly into lipid nanoparticles. Interactions between porphyrins in the nanoparticle lipid membrane changes their photophysical properties. J-aggregation occurs when porphyrins are aligned head-to-tail and results in a dramatic red-shift in the absorption spectrum. Because J-aggregation relies on nanoscale dye–dye ordering it is sensitive to external stimuli that impact membrane structure, including temperature and interactions with biological species. In Chapter 1, porphyrin-lipid nanomedicine is first contextualized within the nanomedicine field. In Chapter 2, a background is provided on the mechanisms that alter the photophysical properties of dyes in nanomedicines and porphyrin J-aggregation is specifically reviewed. Chapter 3 examines the nanostructure-dependent photophysical properties of porphyrin-lipid aggregates in lipid membranes. Chapter 4 investigates the optical stability of J-aggregating porphyrin-lipid nanoparticles during exposure to serum proteins. Chapter 5 explores the potential utility of these J-nanoparticles for phototherapy and optical imaging applications. Lastly, Chapter 6 presents a discussion of new knowledge gained and potential future directions. From these fundamental studies, an assessment is provided of whether the unique nanostructure-dependent photophysical properties of J-nanoparticles are also potentially medically useful.Ph.D