STUDYING INDUCIBLE ENDOTHELIAL LEAKINESS EFFECT BY NANOMATERIALS

Abstract

All intravenously delivered nanoparticles will interact with the body’s vasculature. In addition to transcytotic transport, it was also discovered that nanoparticles themselves can directly induce endothelial leakiness, in a phenomenon known as “nanomaterial-induced endothelial leakiness (NanoEL)”. In this dissertation, NanoEL was explored for both potential therapeutic applications and deciphering novel interactions with endothelia. In the first work, a systematic examination of the descriptors of NanoEL revealed its inducible nature, which facilitated subsequent attempts to employ or study NanoEL. In the second work, nanoparticles of varying sizes and roughness were used to yield a varied intensity of NanoEL, and to actively enhance paracellular transport of therapeutics. In the third work, established nanocluster materials were used to trigger endothelial leakiness, where it was discovered that unprecedentedly small sizes also elicit leakiness. In the fourth work, amyloid protein nanoparticulates were investigated and observed to produce leakiness through a mechanism analogous to NanoEL.