Real-time imaging of oxidative and nitrosative stress in the liver of live animals for drug-toxicity testing.
2014; 32 (4): 373-380
Semiconducting polymer nanoparticles as photoacoustic molecular imaging probes in living mice
2014; 9 (3): 233-239
Current drug-safety assays for hepatotoxicity rely on biomarkers with low predictive power. The production of radical species, specifically reactive oxygen species (ROS) and reactive nitrogen species (RNS), has been proposed as an early unifying event linking the bioactivation of drugs to hepatotoxicity and as a more direct and mechanistic indicator of hepatotoxic potential. Here we present a nanosensor for rapid, real-time in vivo imaging of drug-induced ROS and RNS for direct evaluation of acute hepatotoxicity. By combining fluorescence resonance energy transfer (FRET) and chemiluminescence resonance energy transfer (CRET), our semiconducting polymer-based nanosensor simultaneously and differentially detects RNS and ROS using two optically independent channels. We imaged drug-induced hepatotoxicity and its remediation longitudinally in mice after systemic challenge with acetaminophen or isoniazid. We detected dose-dependent ROS and RNS activity in the liver within minutes of drug challenge, which preceded histological changes, protein nitration and DNA double-strand-break induction.
View details for DOI 10.1038/nbt.2838
View details for PubMedID 24658645
Semiconducting Polymer Nanoprobe for In Vivo Imaging of Reactive Oxygen and Nitrogen Species
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
2013; 52 (39): 10325-10329
Photoacoustic imaging holds great promise for the visualization of physiology and pathology at the molecular level with deep tissue penetration and fine spatial resolution. To fully utilize this potential, photoacoustic molecular imaging probes have to be developed. Here, we introduce near-infrared light absorbing semiconducting polymer nanoparticles as a new class of contrast agents for photoacoustic molecular imaging. These nanoparticles can produce a stronger signal than the commonly used single-walled carbon nanotubes and gold nanorods on a per mass basis, permitting whole-body lymph-node photoacoustic mapping in living mice at a low systemic injection mass. Furthermore, the semiconducting polymer nanoparticles possess high structural flexibility, narrow photoacoustic spectral profiles and strong resistance to photodegradation and oxidation, enabling the development of the first near-infrared ratiometric photoacoustic probe for in vivo real-time imaging of reactive oxygen species-vital chemical mediators of many diseases. These results demonstrate semiconducting polymer nanoparticles to be an ideal nanoplatform for developing photoacoustic molecular probes.
View details for DOI 10.1038/NNANO.2013.302
View details for Web of Science ID 000332637200018
Conjugated Oligoelectrolyte Harnessed Polyhedral Oligomeric Silsesquioxane as Light-Up Hybrid Nanodot for Two-Photon Fluorescence Imaging of Cellular Nucleus
2010; 22 (37): 4186-?
Semiconducting polymer nanoparticles are used as a free-radical inert and light-harvesting nanoplatform for in vivo molecular imaging of reactive oxygen and nitrogen species (RONS). This nanoprobe permits detection of RONS in the microenvironment of spontaneous bacterial infection (see picture; FRET=fluorescence resonance energy transfer).
View details for DOI 10.1002/anie.201303420
View details for Web of Science ID 000329141800033
View details for PubMedID 23943508
Cationic Oligofluorene-Substituted Polyhedral Oligomeric Silsesquioxane as Light-Harvesting Unimolecular Nanoparticle for Fluorescence Amplification in Cellular Imaging
2010; 22 (5): 643-?
A Graphene-Conjugated Oligomer Hybrid Probe for Light-Up Sensing of Lectin and Escherichia Coli
2011; 23 (38): 4386-?
Affibody-Attached Hyperbranched Conjugated Polyelectrolyte for Targeted Fluorescence Imaging of HER2-Positive Cancer Cell
2011; 12 (8): 2966-2974
A water-soluble organic/inorganic hybrid nanodot based on polyhedral oligomeric silsesquioxane (POSS) and conjugated oligoelectrolyte is designed and synthesized for two-photon fluorescence imaging of cellular nucleus, which takes advantage of its small size (?3.3 nm) that imparts nucleus permeability and substantial DNA-enhanced two-photon excited fluorescence that allows illuminating the nucleus with a high contrast.
View details for DOI 10.1002/adma.201001544
View details for Web of Science ID 000283392000013
View details for PubMedID 20589775
Conjugated polyelectrolyte blend as perturbable energy donor-acceptor assembly with multicolor fluorescence response to proteins
2010; 46 (9): 1470-1472
A hyperbranched conjugated polyelectrolyte (HCPE) with a core-shell structure is designed and synthesized via alkyne polycyclotrimerization and click chemistry. The HCPE has an emission maximum at 565 nm with a quantum yield of 12% and a large Stokes shift of 143 nm in water. By virtue of its poly(ethylene glycol) shell, this polymer naturally forms spherical nanoparticles that minimize nonspecific interaction with biomolecules in aqueous solution, consequently allowing for efficient bioconjugation with anti-HER2 affibody via carbodiimide-activated coupling reaction. The resulting affibody-attached HCPE can be utilized as a reliable fluorescent probe for targeted cellular imaging of HER2-overexpressed cancer cells such as SKBR-3. Considering its low cytotoxicity and good photostability, the HCPE nanoprobe holds great promise in practical imaging tasks. This study also provides a molecular engineering strategy to overcome the intrinsic limitations of traditional fluorescent polymers (e.g., chromophore-tethered polymers and linear conjugated polyelectrolytes) for bioconjugation and applications.
View details for DOI 10.1021/bm200563a
View details for Web of Science ID 000293488200014
View details for PubMedID 21710990
Optimizing the cationic conjugated polymer-sensitized fluorescent signal of dye labeled oligonucleotide for biosensor applications
BIOSENSORS & BIOELECTRONICS
2009; 24 (5): 1067-1073
Blending conjugated polyelectrolytes is demonstrated to be a convenient yet effective method to create a perturbable energy transfer systems with multicolor fluorescence response toward both nonmetalloproteins and metalloproteins, which holds great promise in visual protein sensing.
View details for DOI 10.1039/b915984c
View details for Web of Science ID 000274580700025
View details for PubMedID 20162151
Methods for real time, highly selective and sensitive polynucleotide detection are of vast scientific and economic importance. Fluorescence resonance energy transfer (FRET)-based assays which take advantage of the collective response of water-soluble conjugated polymers (CPs) and the self-assembly characteristic of aqueous polyelectrolytes have been widely used for the detection of DNA, RNA, protein and small molecules. The detection sensitivity of CP-based biosensor is dependent on the signal amplification of dye emission upon excitation of CP relative to that upon direct excitation of the dye. Using cationic polyfluorene derivatives and chromophore (fluorescein or Texas Red) labeled single-stranded DNA molecules (ssDNA-C*) as donor/acceptor pairs, we show that in addition to the spectral overlap, orientation and distance between the donor and the acceptor, the energy levels and fluorescence quenching of the donor/acceptor within the polymer/DNA-C* complexes are also important factors that affect the signal output of dye emission.
View details for DOI 10.1016/j.bios.2008.07.029
View details for Web of Science ID 000263199800002
View details for PubMedID 18760913