Junlong Geng

Specific Detection of Integrin αvβ3 by Light-Up Bioprobe with Aggregation-Induced Emission Characteristics

Specific bioprobes with fluorescence turn-on response are highly desirable for high contrast biosensing and imaging. In this work, we developed a new generation bioprobe by integrating tetraphenylsilole, a fluorogenic unit with aggregation-induced emission (AIE) characteristic, with cyclic arginine-glycine-aspartic acid tripeptide (cRGD), a targeting ligand to integrin α(v)β(3) receptor. Emission of the AIE probe is switched on upon its specific binding to integrin α(v)β(3), which allows quantitative detection of integrin α(v)β(3) in solution and real-time imaging of the binding process between cRGD and integrin α(v)β(3) on cell membrane. The probe can be used for tracking integrin α(v)β(3) and for identifying integrin α(v)β(3)-positive cancer cells.

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.

Lipid-PEG-Folate Encapsulated Nanoparticles with Aggregation Induced Emission Characteristics: Cellular Uptake Mechanism and Two-Photon Fluorescence Imaging

Folate functionalized nanoparticles (NPs) that contain fluorogens with aggregation-induced emission (AIE) characteristics are fabricated to show bright far-red/near-infrared fluorescence, a large two-photon absorption cross section and low cytotoxicity, which are internalized into MCF-7 cancer cells mainly through caveolae-mediated endocytosis. One-photon excited in vivo fluorescence imaging illustrates that these AIE NPs can accumulate in a tumor and two-photon excited ex vivo tumor tissue imaging reveals that they can be easily detected in the tumor mass at a depth of 400 μm. These studies indicate that AIE NPs are promising alternatives to conventional TPA probes for biological imaging.

Biocompatible Conjugated Polymer Nanoparticles for Efficient Photothermal Tumor Therapy

Conjugated polymers (CPs) with strong near-infrared (NIR) absorption and high heat conversion efficiency have emerged as a new generation of photothermal therapy (PTT) agents for cancer therapy. An efficient strategy to design NIR absorbing CPs with good water dispersibility is essential to achieve excellent therapeutic effect. In this work, poly[9,9-bis(4-(2-ethylhexyl)phenyl)fluorene-alt-co-6,7-bis(4-(hexyloxy)phenyl)-4,9-di(thiophen-2-yl)-thiadiazoloquinoxaline] (PFTTQ) is synthesized through the combination of donor-acceptor moieties by Suzuki polymerization. PFTTQ nanoparticles (NPs) are fabricated through a precipitation approach using 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000] (DSPE-PEG2000 ) as the encapsulation matrix. Due to the large NIR absorption coefficient (3.6 L g(-1) cm(-1) ), the temperature of PFTTQ NP suspension (0.5 mg/mL) could be rapidly increased to more than 50 °C upon continuous 808 nm laser irradiation (0.75 W/cm(2) ) for 5 min. The PFTTQ NPs show good biocompatibility to both MDA-MB-231 cells and Hela cells at 400 μg/mL of NPs, while upon laser irradiation, effective cancer cell killing is observed at a NP concentration of 50 μg/mL. Moreover, PFTTQ NPs could efficiently ablate tumor in in vivo study using a Hela tumor mouse model. Considering the large amount of NIR absorbing CPs available, the general encapsulation strategy will enable the development of more efficient PTT agents for cancer or tumor therapy.

A tetraphenylethene-based red luminophor for an efficient non-doped electroluminescence device and cellular imaging

An efficient red luminophor (TTPEBTTD) consisting of a 4,7-di(thiophen-2-yl)benzo-2,1,3-thiadiazole core and tetraphenylethene peripheries is developed. The non-doped electroluminescence device based on TTPEBTTD radiates red light with high efficiency up to 3.7%. The nanoparticles of TTPEBTTD are promising fluorescent visualizers for cellular imaging with low cytotoxicity.

Eccentric Loading of Fluorogen with Aggregation-Induced Emission in PLGA Matrix Increases Nanoparticle Fluorescence Quantum Yield for Targeted Cellular Imaging

A simple strategy is developed to prepare eccentrically or homogeneously loaded nanoparticles (NPs) using poly (DL-lactide-co-glycolide) (PLGA) as the encapsulation matrix in the presence of different amounts of polyvinyl alcohol (PVA) as the emulsifier. Using 2,3-bis(4-(phenyl(4-(1,2,2-triphenylvinyl)-phenyl)amino)-phenyl)-fumaronitrile (TPETPAFN), a fluorogen with aggregation-induced emission (AIE) characteristics, as an example, the eccentrically loaded PLGA NPs show increased fluorescence quantum yields (QYs) as compared to the homogeneously loaded ones. Field emission transmission electron microscopy and fluorescence lifetime measurements reveal that the higher QY of the eccentrically loaded NPs is due to the more compact aggregation of AIE fluorogens that restricts intramolecular rotations of phenyl rings, which is able to more effectively block the non-radiative decay pathways. The eccentrically loaded NPs show far red/near infrared emission with a high fluorescence QY of 34% in aqueous media. In addition, by using poly([lactide-co-glycolide]-b-folate [ethylene glycol]) (PLGA-PEG-folate) as the co-encapsulation matrix, the obtained NPs are born with surface folic acid groups, which are successfully applied for targeted cellular imaging with good photostability and low cytotoxicity. Moreover, the developed strategy is also demonstrated for inorganic-component eccentrically or homogeneously loaded PLGA NPs, which facilitates the synthesis of polymer NPs with controlled internal architectures.

PEGylated conjugated polyelectrolytes containing 2,1,3-benzoxadiazole units for targeted cell imaging

Two amphiphilic conjugated polyelectrolytes (CPEs) were designed and synthesized via a post-polymerization strategy. A neutral precursor polymer of poly(9,9-bis(6′-azidohexyl)fluorene-alt-2,1,3-benzoxadiazole) (PFBD-N3) was synthesized first through Suzuki polymerization, which was followed by click reaction to incorporate dense poly(ethylene glycol) (PEG) to afford PFBD-PEG600-COOH and PFBD-PEG2000-COOH, respectively. The CPEs show better solubility in water with increasing PEG chain length due to the increased hydrophilicity of longer PEG chains. Both CPEs formed nanoparticles (NPs) in water and were used as cellular probes for visualization of HT-29 cancer cells. As compared to PFBD-PEG600-COOH NPs, PFBD-PEG2000-COOH NPs were less efficiently taken up by cells due to the longer PEG side chains, which significantly inhibited nonspecific cellular uptake. Further conjugation of PFBD-PEG2000-COOH with c(RGDfK) yielded PFBD-PEG2000-RGD NPs as a specific cellular probe for targeted cancer cell imaging. Preliminary study revealed that PFBD-PEG2000-RGD NPs were favorable for targeted cellular imaging with low cytotoxicity, high selectivity and good photostability.

Water-soluble Bioprobes with Aggregation-induced Emission Characteristics for Light-up Sensing of Heparin

Two water-soluble cationic fluorene-based fluorescent probes for heparin detection are designed and synthesized. A slight change in the molecular design results in two probes with opposite optical properties in their solution and aggregation states as well as a response to heparin in buffer solution. The probe with a propeller-like conformation exhibits aggregation-induced emission (AIE) characteristics and shows a green fluorescence enhancement upon interaction with heparin; in contrast, the probe with a more planar conformation has a fluorescence quenching response. A comprehensive study on heparin detection using the two probes was conducted, which revealed that the AIE probe shows a better performance than the aggregation-caused quenching (ACQ) probe in terms of sensitivity. The AIE probe integrated with graphene oxide (GO) further improves the heparin detection sensitivity and selectivity. The solution of AIE probe/GO emits strong green fluorescence only in the presence of heparin, which allows for light-up visual discrimination of heparin from its analogues such as chondroitin-4-sulfate and hyaluronic acid. Moreover, the linear light-up response of AIE probe/GO enables heparin quantification in the range of 0-13.2 μM with a detection limit of 10 nM, which is of practical importance for heparin monitoring during surgery or therapy.

Multifunctional Conjugated Polymer Nanoparticles for Image‐Guided Photodynamic and Photothermal Therapy

A multifunctional theranostic platform based on conjugated polymer nanoparticles (CPNs) with tumor targeting, fluorescence detection, photodynamic therapy (PDT), and photothermal therapy (PTT) is developed for effective cancer imaging and therapy. Two conjugated polymers, poly[9,9-bis(2-(2-(2-methoxyethoxy)ethoxy)-ethyl)fluorenyldivinylene]-alt-4,7-(2,1,3-benzothiadiazole) with bright red emission and photosensitizing ability and poly[(4,4,9,9-tetrakis(4-(octyloxy)phenyl)-4,9-dihydro-s-indacenol-dithiophene-2,7-diyl)-alt-co-4,9-bis(thiophen-2-yl)-6,7-bis(4-(hexyloxy)phenyl)-thiadiazolo-quinoxaline] with strong near-infrared absorption and excellent photothermal conversion ability are co-loaded into one single CPN via encapsulation approach using lipid-polyethylene glycol as the matrix. The obtained co-loaded CPNs show sizes of around 30 nm with a high singlet oxygen quantum yield of 60.4% and an effective photothermal conversion efficiency of 47.6%. The CPN surface is further decorated with anti-HER2 affibody, which bestows the resultant anti-HER2-CPNs superior selectivity toward tumor cells with HER2 overexpression both in vitro and in vivo. Under light irradiation, the PDT and PTT show synergistic therapeutic efficacy, which provides new opportunities for the development of multifunctional biocompatible organic materials in cancer therapy.