Biological applications and delivery of non-conventional fluorophores

Abstract

Our ability to see inside living cells has largely been achieved through the use of small fluorescent molecules. Fluorescent imaging has provided a way to non-invasively monitor the location of organelles and biomolecules in their native environments with high spatial and temporal resolution. In particular, fluorescent probes with emission wavelengths in the far-red to near-infrared (FR/NIR) region are highly coveted in vivo bioimaging agents because tissue exhibits low optical absorption and weak intrinsic autofluorescence in the FR/NIR spectral range. Most conventional FR/NIR fluorescent probes available on the commercial market are organic dyes which are typically encapsulated within a nanoparticle to enhance biostability, photostability and cellular uptake. However, conventional organic dyes suffer from a phenomenon known as aggregation-caused quenching (ACQ). A seminal finding by our lab revealed a new class of non-conventional propeller-shaped fluorophores which have photophysical properties that are diametrically opposite to the ACQ effect due to the restriction of intramolecular motion. Since our initial report of aggregation-induced emission (AIE), many research groups have focused on designing new FR/NIR emissive AIE compounds (AIEgens) and pure organic room-temperature phosphorescent nanocrystals (RTP NCs) for bioimaging applications. In this thesis, we build on these established design principles to create a series of novel FR/NIR AIEgens and RTP NCs. We examined the photophysical and non-linear optical properties of these molecules. We discovered that the cellular uptake of FR/NIR AIEgens and RTP NCs is extremely challenging due to their large molecular size. In order to find biological applications for these interesting molecules, we experimented with new targeted and untargeted delivery systems including biotin-PEG and saponin nanoparticle (NP) based delivery systems. In particular, we found the saponin delivery systems to be biocompatible, inexpensive, ultrafast and applicable to deliver a wide variety of FR/NIR AIEgen NPs and RTP NCs into both mammalian and plant cells.

Date of Award	2018
Original language	English
Awarding Institution	The Hong Kong University of Science and Technology