Lipid droplets are highly associated with obesity, diabetes, inflammatory disorders and cancer. A reliable two-photon dye for specific lipid droplets imaging in live cells and live tissues at ultra-low concentration has rarely been reported. In this work, four new aggregation-induced emission luminogens (AIEgens) based on the naphthalene core were designed and synthesized for specific two-photon lipid droplets staining. The new molecules, namely NAP AIEgens, exhibit large Stokes shift (>110 nm), high solid-state fluorescence quantum yield (up to 30%), good two-photon absorption cross section (45-100 GM at 860 nm), high biocompatibility and good photostability. They could specifically stain lipid droplets at ultra-low concentration (50 nM) in a short time of 15 min. Such ultra-low concentration is the lowest value for lipid droplets staining in live cells reported so far. In vitro and ex vivo two-photon imaging of lipid droplets in live cells and live mice liver tissues were successfully demonstrated. In addition, selective visualization of lipid droplets in live mice liver tissues could be achieved at a depth of about 70 μm. These excellent properties render them as promising candidates for investigating lipid droplets-associated physiological and pathological processes in live biological samples.

Saponins are a class of naturally occurring bioactive and biocompatible amphiphilic glycosides produced by plants. Some saponins, such as α-hederin, exhibit unique cell membrane interactions. At concentrations above their critical micelle concentration, they will interact and aggregate with membrane cholesterol to form transient pores in the cell membrane. In this project, we utilized the unique permeabilization and amphiphilic properties of saponins for the intracellular delivery of deep-red-emitting aggregation-induced emission nanoparticles (AIE NPs) and pure organic room-temperature phosphorescent nanocrystals (NCs). We found this method to be biocompatible, inexpensive, ultrafast, and applicable to deliver a wide variety of AIE NPs and NCs into cancer cells.

Impairment of microglial clearance activity contributes to beta-amyloid (Ab) pathology in Alzheimer's disease (AD). While the transcriptome profile of microglia directs microglial functions, how the microglial transcriptome can be regulated to alleviate AD pathology is largely unknown. Here, we show that injection of interleukin (IL)-33 in an AD transgenic mouse model ameliorates Ab pathology by reprogramming microglial epigenetic and transcriptomic profiles to induce a microglial subpopulation with enhanced phagocytic activity. These IL-33-responsive microglia (IL-33RMs) express a distinct transcriptome signature that is highlighted by increased major histocompatibility complex class II genes and restored homeostatic signature genes. IL-33induced remodeling of chromatin accessibility and PU.1 transcription factor binding at the signature genes of IL-33RM control their transcriptome reprogramming. Specifically, disrupting PU.1-DNA interaction abolishes the microglial state transition and Ab clearance that is induced by IL-33. Thus, we define a PU.1-dependent transcriptional pathway that drives the IL-33-induced functional state transition of microglia, resulting in enhanced Ab clearance.