Rongrong Liu

Photostable fluorescent organic dots with aggregation-induced emission (AIE dots) for noninvasive long-term cell tracing

Long-term noninvasive cell tracing by fluorescent probes is of great importance to life science and biomedical engineering. For example, understanding genesis, development, invasion and metastasis of cancerous cells and monitoring tissue regeneration after stem cell transplantation require continual tracing of the biological processes by cytocompatible fluorescent probes over a long period of time. In this work, we successfully developed organic far-red/near-infrared dots with aggregation-induced emission (AIE dots) and demonstrated their utilities as long-term cell trackers. The high emission efficiency, large absorptivity, excellent biocompatibility, and strong photobleaching resistance of the AIE dots functionalized by cell penetrating peptides derived from transactivator of transcription proteins ensured outstanding long-term noninvasive in vitro and in vivo cell tracing. The organic AIE dots outperform their counterparts of inorganic quantum dots, opening a new avenue in the development of fluorescent probes for following biological processes such as carcinogenesis.

Ultrabright Organic Dots with Aggregation‐Induced Emission Characteristics for Real‐Time Two‐Photon Intravital Vasculature Imaging

Ultrabright organic dots with aggregation-induced emission characteristics (AIE dots) are prepared and shown to exhibit a high quantum yield, a, large two-photon absorption cross-section, and low in vivo toxicity. Real-time two-photon intravital blood vascular imaging in various tissues substantiates that the AIE dots are effective probes for in vivo vasculature imaging in a deep and high-contrast manner.

Precise and Long-Term Tracking of Adipose-Derived Stem Cells and Their Regenerative Capacity via Superb Bright and Stable Organic Nanodots

Monitoring and understanding long-term fate and regenerative therapy of administrated stem cells in vivo is of great importance. Herein we report organic nanodots with aggregation-induced emission characteristics (AIE dots) for long-term tracking of adipose-derived stem cells (ADSCs) and their regenerative capacity in living mice. The AIE dots possess high fluorescence (with a high quantum yield of 25±1%), excellent biological and photophysical stabilities, low in vivo toxicity, and superb retention in living ADSCs with negligible interference on their pluripotency and secretome. These AIE dots also exhibit superior in vitro cell tracking capability compared to the most popular commercial cell trackers, PKH26 and Qtracker 655. In vivo quantitative studies with bioluminescence and GFP labeling as the controls reveal that the AIE dots can precisely and quantitatively report the fate of ADSCs and their regenerative capacity for 42 days in an ischemic hind limb bearing mouse model.

Ultrabright organic dots with aggregation-induced emission characteristics for cell tracking.

Noninvasive fluorescence cell tracking provides critical information on the physiological displacement and translocation of actively migrating cells, which deepens our understanding of biomedical engineering, oncological research, stem cell transplantation and therapies. Non-viral fluorescent protein transfection based cell tracing has been widely used but with issues related to cell type-dependent expression, lagged readout, immunogenicity and mutagenesis. Alternative cell tracking methods are therefore desired to attain reliable, stable, and efficient labeling over a long time. In this work, we have successfully developed ultra-bright organic dots with aggregation-induced emission (AIE dots) and demonstrated their capabilities for cellular imaging and cell tracking. The AIE dots possess high fluorescence, super photostability, and excellent cellular retention and biocompatibility. As compared to commonly used pMAX-GFP plasmid labeling approach, the organic AIE dots showed excellent cell labeling on all tested human cell lines and superior tracing performance, which opens up new opportunities in the cell-based immunotherapies and other related biological researches.

A Multifunctional Probe with Aggregation-Induced Emission Characteristics for Selective Fluorescence Imaging and Photodynamic Killing of Bacteria Over Mammalian Cells

A multifunctional probe aggregation-induced emission-Zinc(II)-dipicolylamine (AIE-ZnDPA) is developed for selective targeting, fluorescence imaging, and photodynamic killing of both Gram-positive and Gram-negative bacteria over mammalian cells. The probe has significant advantages in simple probe design, enhanced fluorescence upon bacteria binding, excellent photostability, and broad-spectrum antibacterial activity with almost no harm to mammalian cells.

Tau-mediated iron export prevents ferroptotic damage after ischemic stroke

Functional failure of tau contributes to age-dependent, iron-mediated neurotoxicity, and as iron accumulates in ischemic stroke tissue, we hypothesized that tau failure may exaggerate ischemia–reperfusion-related toxicity. Indeed, unilateral, transient middle cerebral artery occlusion (MCAO) suppressed hemispheric tau and increased iron levels in young (3-month-old) mice and rats. Wild-type mice were protected by iron-targeted interventions: ceruloplasmin and amyloid precursor protein ectodomain, as well as ferroptosis inhibitors. At this age, tau-knockout mice did not express elevated brain iron and were protected against hemispheric reperfusion injury following MCAO, indicating that tau suppression may prevent ferroptosis. However, the accelerated age-dependent brain iron accumulation that occurs in tau-knockout mice at 12 months of age negated the protective benefit of tau suppression against MCAO-induced focal cerebral ischemia–reperfusion injury. The protective benefit of tau knockout was revived in older mice by iron-targeting interventions. These findings introduce tau–iron interaction as a pleiotropic modulator of ferroptosis and ischemic stroke outcome.

Bright Quantum‐Dot‐Sized Single‐Chain Conjugated Polyelectrolyte Nanoparticles: Synthesis, Characterization and Application for Specific Extracellular Labeling and Imaging

We report a simple method to fabricate quantum-dot-sized nanoparticles (NPs) from poly[9,9-bis((6-N,N,N-trimethylammonium)hexyl)fluorene-alt-co-2,1,3-benzo-xadiazole dibromide] (PFBD). The transmission electron microscope results reveal that the obtained NPs have a mean diameter of ≈4 nm, which is composed of a single PFBD chain. The NPs show bright fluorescence with an emission maximum at ≈636 nm and a quantum yield of ≈26% in water. The fluorescence properties of the NPs are characterized by steady fluorescence microscopy, fluorescence dynamic study and single nanoparticle microscopy, which show superior brightness over commercial quantum dots QD655. The NPs are further conjugated with streptavidin to yield PFBD-SA NPs, which serve as a specific extracellular labeling and imaging probe with high specificity and good photostability.

Ultrasmall Conjugated Polymer Nanoparticles with High Specificity for Targeted Cancer Cell Imaging

Fluorescent and biocompatible organic nanoparticles have attracted great interest in cancer detection and imaging, but the nonspecific cellular uptake has limited the detection specificity and sensitivity. Herein, the authors report the ultrasmall conjugated polymer nanoparticles (CPNs) with bright far‐red/near‐infrared emission for targeted cancer imaging with high specificity. The sizes of the ultrasmall CPNs are around 6 nm (CPN6), while large CPNs show sizes around 30 nm (CPN30). Moreover, CPN6 exhibits largely improved fluorescence quantum yield (η) of 41% than CPN30 (25%). Benefiting from the ultrasmall size, bare CPN6 shows largely suppressed nonspecific cellular uptake as compared to CPN30, while cyclic arginine‐glycine‐aspartic acid (cRGD) functionalized CPN6 (cRGD‐CPN6) possesses excellent selectivity toward αvβ 3 integrin overexpressed MDA‐MB‐231 cells over other cells in cell mixtures. The faster body clearance of CPN6 over CPN30 indicates its greater potentials as a noninvasive nanoprobe for in vivo and practical applications.

Stretching and Imaging of Single DNA Chains on a Hydrophobic Polymer Surface Made of Amphiphilic Alternating Comb-Copolymer

Functionalization of amine derivatized glass slides with a poly(maleic anhydride)-based comb-copolymer to facilitate stretching, aligning, and imaging of individual dsDNA chains is presented. The polymer-coated surface is hydrophobic due to the presence of the long alkyl side chains along the polymer backbone. The surface is also characterized by low roughness and a globular morphology. Stretched and aligned bacteriophage λ-DNA chains were obtained using a robust method based on stretching by a receding water meniscus at pH 7.8 without the need for small droplet volumes or precoating the surface with additional layers of (bio)molecules. Although the dye to DNA base pairs ratio did not influence substantially the stretching length distributions, a clear peak at stretching lengths close to the contour length of the dsDNA is visible at larger staining ratios.