Meijuan Jiang

Mitochondrial Imaging with Combined Fluorescence and Stimulated Raman Scattering Microscopy Using a Probe of the Aggregation-Induced Emission Characteristic

In vivo quantitative measurement of biodistribution plays a critical role in the drug/probe development and diagnosis/treatment process monitoring. In this work, we report a probe, named AIE-SRS-Mito, for imaging mitochondria in live cells via fluorescence (FL) and stimulated Raman scattering (SRS) imaging. The probe features an aggregation-induced emission (AIE) characteristic and possesses an enhanced alkyne Raman peak at 2223 cm-1. The dual-mode imaging of AIE-SRS-Mito for selective mitochondrion-targeting was examined on a homemade FL-SRS microscope system. The detection limit of the probe in the SRS imaging was estimated to be 8.5 μM. Due to the linear concentration dependence of SRS and inertness of the alkyne Raman signal to environmental changes, the intracellular distribution of the probe was studied, showing a local concentration of >2.0 mM in the mitochondria matrix, which was >100-fold higher than the incubation concentration. To the best of our knowledge, this is the first time that the local concentration of AIE molecules inside cells has been measured noninvasively and directly. Also, the nonquenching effect of such AIE molecules in cell imaging has been verified by the positive correlation of FL and SRS signals. Our work will encourage the utilization of SRS microscopy for quantitative characterization of FL probes or other nonfluorescent compounds in living biological systems and the development of FL-SRS dual-mode probes for specific biotargets.

A simple mitochondrial targeting AIEgen for image-guided two-photon excited photodynamic therapy

Two-photon excited photodynamic therapy (TP-PDT) is not only able to offer deeper penetration depth but also much more precise 3D treatment than traditional one-photon excited PDT. However, the achievement of TP-PDT requires photosensitizers with large two-photon absorption cross sections, efficient generation of reactive oxygen species, and bright two-photon fluorescence. In this work, we present a simple AIE luminogen (AIEgen), IQ-TPA, with mitochondrial targeting and susceptible two-photon excitation for image-guided photodynamic therapy in cancer cells. This feasibility of utilizing small molecular multifunctional AIEgens for TP-PDT was demonstrated together with the merits of tiny size, good cell permeability, low dark cytotoxicity and easy synthesis, showing great potential for the development of future theranostic systems.

Dendritic nanotubes self-assembled from stiff polysaccharides as drug and probe carriers

Dendritic nanotubes (DNTs) with hydrophobic cavities were constructed directly from rigid branched β-1,3-d-glucan (AF1) in aqueous solution, and the AF1 sample was isolated from the fruiting bodies of Auricularia auricula-judae, a household nutritional food. The structure of AF1 dendritic nanotubes was demonstrated with a transmission electron microscope (TEM) and a scanning electron microscope (SEM), and a schematic diagram was proposed to describe the formation process, which was supported by the results of static/dynamic light scattering (SLS/DLS) and atomic force microscopy (AFM). In solution, a sequential self-assembly of the AF1 chains in a parallel manner occurred to form lamellas followed by self-curling into nanotubes with the mean diameters from 20 to 80 nm, depending on the concentration and molecular weight of AF1, through hydrogen bonding and hydrophilic/hydrophobic interaction. As a result of the dendritic structure, the AF1 aggregates exhibited highly condensed hydrophobic regions, which could be used as carriers to achieve a high concentration of the target molecules. In our findings, the anticancer drug DOX and the fluorescent probe TPA-BMO could be loaded into the hydrophobic region of DNTs. Interestingly, DOX-loaded DNTs of AF1 exhibited high drug loading capacity and pH-triggered sustained release behaviors (>23 days) with reduced cytotoxicity in vitro. Moreover, the bioimaging experiment demonstrated that TPA-BMO-loaded DNTs of AF1 induced stronger fluorescence intensity than TPA-BMO alone, and maintained a longer duration time (18 days) in vivo. Therefore, the DNTs of AF1 have promising applications as bioactive carriers, especially in the fields of drug delivery and bioimaging.

Development of benzylidene-methyloxazolone based AIEgens and decipherment of their working mechanism

Based on an analogue of green fluorescent protein chromophore benzylidene-methyloxazolone (BMO), a series of fluorophores with an additional phenyl group, BMO-PH, BMO-PF, BMO-PM and BMO-PC, have been prepared and are found to be AIE-active. Their solutions are weakly emissive and their aggregation or solid states are highly emissive. Although these compounds readily undergo efficient E/Z isomerization (EZI) upon UV irradiation in solution, the intramolecular rotation around the double bond and phenyl rotation around the single bond serve as the key non-radiative decay channels to dissipate the excited-state energies. The EZI is only the phenomenal result. In aggregates, these intramolecular motions are greatly restricted by multiple intermolecular interactions, resulting in the AIE effect. To ensure a high solid-state quantum yield, prevention of detrimental π–π stacking is of essence. An additional phenyl group to BMO is found to increase the π–π distance and weaken the π–π interaction. Thus, the quantum yields are increased. Strong electron-donating groups and extended conjugation are effective at tuning the emission color bathochromically. Based on these principles, we succeeded in increasing the solid-state quantum yield up to 50% and obtaining a red emission maximum of 635 nm. Moreover, these compounds are promising for applications in photoswitches and fluorescent patterns, and their crystals are good candidates for luminescent waveguides with low light loss efficiency.

The unusual aggregation-induced emission of coplanar organoboron isomers and their lipid droplet-specific applications

Luminogens with aggregation-induced emission (AIE) characteristics generally possess twisted structures to prevent emission quenching in the solid state by π–π stacking interactions. In this work, new organoboron derivatives with coplanar structures were synthesized and found to be AIE-active. Analysis by photoluminescence spectroscopy, single crystal X-ray diffraction and theoretical calculations depicted that the distinct luminescence behaviors of the molecules stemmed from the different extent of excited-state double-bond reorganization (ESDBR), which consumed the energy of the excitons through non-radiative pathways. This process was restricted in a highly viscous medium or in the solid state to enable the molecules to emit efficiently. The organoboron derivatives based on the ESDBR mechanism not only provide a new strategy to design coplanar AIE luminogens but also act as biological probes excellently and specifically targeting lipid droplets.

A fluorescent sensor array for highly efficient microbial lysates identification through competitive interactions

Optical cross-reactive sensor arrays have recently been proven to be a powerful tool for high-throughput bioanalytes identification. Nevertheless, identification and classification of microbes, especially using microbial lysates as the analytes, still is a great challenge due to their complex composition. Herein, we achieve this goal by using luminogens featuring aggregation-induced emission characteristics (AIEgens) and graphene oxide (GO) to construct a microbial lysate responsive fluorescent sensor array. The combination of AIEgen with GO not only reduces the background signal but also induces the competition interactions among AIEgen, microbial lysates, and GO, which highly improves the discrimination ability of the sensor array. As a result, six microbes, including two fungi, two Gram-positive bacteria, and two Gram-negative bacteria are precisely identified. Thus, this work provides a new way to design safer and simpler sensor arrays for the discrimination of complex analytes.

Aggregation-Induced Emission Luminogens as Color Converters for Visible-Light Communication

In this work, we report the application of the aggregation-induced emission luminogens (AIEgens) as color converters for visible light communication (VLC). In the form of pure solid powder, the AIEgens studied herein have demonstrated blue-to-red full-color emissions, large -6 dB electrical modulation bandwidths up to 279 MHz (∼56× that of commercial phosphor), and most of them can achieve high data rates of 428-493 Mbps (up to ∼49× that of commercial phosphor) at a maximum bit error rate of 3.8 × 10-3 using on-off keying. Their data communication performances strongly suggest that AIEgens are very promising candidates as color converters for VLC applications, together with their unique AIE properties that will benefit usage in high concentration. Based on the comprehensive experimental results, we further propose some insights into improving data rate of the color converter in VLC: the data rate limit is influenced by modulation bandwidth and signal-noise ratio (SNR). We have experimentally proved that the -6 dB electrical modulation bandwidth f c can be estimated from the effective lifetime τ of the color converter with the theoretical prediction of [Formula: see text] within experimental uncertainties, while theoretically derived that the SNR is proportional to its PL quantum efficiency. These observations and implications are very profound for exploring materials as color converters and improve the data transmission performance in VLC.