Amyloid Targeting Red Emitting AIE Dots for Diagnostic and Therapeutic Application against Alzheimer's Disease.

The emergence of neurodegenerative diseases is connected to several pathogenic factors, including metal ions, amyloidogenic proteins, and reactive oxygen species. Recent studies suggest that cytotoxicity is caused by the small, dynamic, and metastable nature of early stage oligomeric species. This work introduces a small molecule-based red-emitting probe with smart features such as increased reactivities against multiple targets, metal-free amyloid-ß (Aß), and metal-bound amyloid-ß (Aß), and most importantly, early stage oligomeric species which are associated with the most common and widespread type of dementia, Alzheimer's disease (AD). Theoretical analyses like molecular dynamics simulation and molecular docking were performed to confirm the reactivity of the molecule toward Aß and found some excellent interactions between the molecule and the peptide. The in vitro and cellular studies demonstrated that this highly biocompatible molecule effectively reduces the structural damage to mitochondria while shielding cells from apoptosis, scavenges ROS (reactive oxygen species), and attenuates multifaceted amyloid toxicity.

Luminescent AIE Dots for Anticancer Photodynamic Therapy.

Photodynamic therapy (PDT) is an emerging effective strategy for cancer treatment. Compared with conventional cancer therapies, such as surgery, chemotherapy, and radiotherapy, PDT has shown great promise as a next-generation cancer therapeutic strategy owing to its many advantages such as non-invasiveness, negligible observed drug resistance, localized treatment, and fewer side effects. One of the key elements in photodynamic therapy is the photosensitizer (PS) which converts photons into active cytotoxic species, namely, reactive oxygen species (ROS). An ideal PS for photodynamic therapy requires the efficient generation of ROS, high stability against photo bleaching, and robust performance in different environments and concentrations. PSs with aggregation-induced emission (AIE) characteristics have drawn significant attention, in that they can overcome the aggregation- caused quenching effect that is commonly seen in the case of fluorescence dyes and provide excellent performance at high concentrations or in their condensed state. Moreover, organic nanomaterials with AIE characteristics, or AIE dots, have played an increasingly significant role in assisting PDT based on its excellent ROS generation efficiency and simultaneous imaging feature. This review summarizes the recent advances on the molecular design of AIE PSs and AIE dots-based probes, as well as their emerging applications for enhanced anticancer PDT theranostics.

NIR-II fluorescence in vivo confocal microscopy with aggregation-induced emission dots.

Significantly reduced tissue scattering of fluorescence signals in the second near-infrared (NIR-II, 1,000-1,700 nm) spectral region offers opportunities for large-depth in vivo bioimaging. Nowadays, most reported works concerning NIR-II fluorescence in vivo bioimaging are realized by wide-field illumination and 2D-arrayed detection (e.g., via InGaAs camera), which has high temporal resolution but limited spatial resolution due to out-of-focus signals. Combining NIR-II fluorescence imaging with confocal microscopy is a good approach to achieve high-spatial resolution visualization of biosamples even at deep tissues. In this presented work, a NIR-II fluorescence confocal microscopic system was setup. By using a kind of aggregation-induced emission (AIE) dots as NIR-II fluorescent probes, 800 µm-deep 3D in vivo cerebrovascular imaging of a mouse was obtained, and the spatial resolution at 700 µm depth could reach 8.78 µm. Moreover, the time-correlated single photon counting (TCSPC) technique and femtosecond laser excitation were introduced into NIR-II fluorescence confocal microscopy, and in vivo confocal NIR-II fluorescence lifetime microscopic imaging (FLIM) of mouse cerebral vasculature was successfully realized.

Gadolinium-functionalized aggregation-induced emission dots as dual-modality probes for cancer metastasis study.

Understanding the localization and engraftment of tumor cells at postintravasation stage of metastasis is of high importance in cancer diagnosis and treatment. Advanced fluorescent probes and facile methodologies for cell tracing play a key role in metastasis studies. In this work, we design and synthesize a dual-modality imaging dots with both optical and magnetic contrast through integration of a magnetic resonance imaging reagent, gadolinium(III), into a novel long-term cell tracing probe with aggregation-induced emission (AIE) in far-red/near-infrared region. The obtained fluorescent-magnetic AIE dots have both high fluorescence quantum yield (25%) and T1 relaxivity (7.91 mM(-1) s(-1) ) in aqueous suspension. After further conjugation with a cell membrane penetrating peptide, the dual-modality dots can be efficiently internalized into living cells. The gadolinium(III) allows accurate quantification of biodistribution of cancer cells via intraveneous injection, while the high fluorescence provides engraftment information of cells at single cellular level. The dual-modality AIE dots show obvious synergistic advantages over either single imaging modality and hold great promises in advanced biomedical studies.