Kanyi Pu

Semiconducting polymer nanoparticles as photoacoustic molecular imaging probes in living mice

Photoacoustic (PA) 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, PA molecular imaging probes have to be developed. Herein we introduce near infrared (NIR) light absorbing semiconducting polymer nanoparticles (SPNs) as a new class of contrast agents for PA molecular imaging. SPNs can produce stronger signal than commonly used single-wall carbon nanotubes and gold nanorods on a per mass basis, permitting whole-body lymph node PA mapping in living mice at a low systematic injection mass. Furthermore, SPNs possess high structural flexibility, narrow PA spectral profiles, and strong resistance to photodegradation and oxidation, which enables development of the first NIR ratiometric PA probe for in vivo real-time imaging of reactive oxygen species—vital chemical mediators of many diseases. These results demonstrate SPNs an ideal nanoplatform for developing PA molecular probes.

Conjugated-Polyelectrolyte-Functionalized Reduced Graphene Oxide with Excellent Solubility and Stability in Polar Solvents

Conjugated-polyelectrolyte (CPE)-functionalized reduced graphene oxide (rGO) sheets are synthesized for the first time by taking advantage of a specially designed CPE, PFVSO(3), with a planar backbone and charged sulfonate and oligo(ethylene glycol) side chains to assist the hydrazine-mediated reduction of graphene oxide (GO) in aqueous solution. The resulting CPE-functionalized rGO (PFVSO(3)-rGO) shows excellent solubility and stability in a variety of polar solvents, including water, ethanol, methanol, dimethyl sulfoxide, and dimethyl formamide. The morphology of PFVSO(3)-rGO is studied by atomic force microscopy, X-ray diffraction, and transmission electron microscopy, which reveal a sandwich-like nanostructure. Within this nanostructure, the backbones of PFVSO(3) stack onto the basal plane of rGO sheets via strong pi-pi interactions, while the charged hydrophilic side chains of PFVSO(3) prevent the rGO sheets from aggregating via electrostatic and steric repulsions, thus leading to the solubility and stability of PFVSO(3)-rGO in polar solvents. Optoelectronic studies show that the presence of PFVSO(3) within rGO induces photoinduced charge transfer and p-doping of rGO. As a result, the electrical conductivity of PFVSO(3)-rGO is not only much better than that of GO, but also than that of the unmodified rGO.

Real-time imaging of oxidative and nitrosative stress in the liver of live animals for drug-toxicity testing

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.

Intraparticle Molecular Orbital Engineering of Semiconducting Polymer Nanoparticles as Amplified Theranostics for in Vivo Photoacoustic Imaging and Photothermal Therapy

Optical theranostic nanoagents that seamlessly and synergistically integrate light-generated signals with photothermal or photodynamic therapy can provide opportunities for cost-effective precision medicine, while the potential for clinical translation requires them to have good biocompatibility and high imaging/therapy performance. We herein report an intraparticle molecular orbital engineering approach to simultaneously enhance photoacoustic brightness and photothermal therapy efficacy of semiconducting polymer nanoparticles (SPNs) for in vivo imaging and treatment of cancer. The theranostic SPNs have a binary optical component nanostructure, wherein a near-infrared absorbing semiconducting polymer and an ultrasmall carbon dot (fullerene) interact with each other to induce photoinduced electron transfer upon light irradiation. Such an intraparticle optoelectronic interaction augments heat generation and consequently enhances the photoacoustic signal and maximum photothermal temperature of SPNs by 2.6- and 1.3-fold, respectively. With the use of the amplified SPN as the theranostic nanoagent, it permits enhanced photoacoustic imaging and photothermal ablation of tumor in living mice. Our study thus not only introduces a category of purely organic optical theranostics but also highlights a molecular guideline to amplify the effectiveness of light-intensive imaging and therapeutic nanosystems.

Diketopyrrolopyrrole-Based Semiconducting Polymer Nanoparticles for In Vivo Photoacoustic Imaging.

Diketopyrrolopyrrole-based semiconducting polymer nanoparticles with high photostability and strong photoacoustic brightness are designed and synthesized, which results in 5.3-fold photoacoustic signal enhancement in tumor xenografts after systemic administration.

A Graphene–Conjugated Oligomer Hybrid Probe for Light‐Up Sensing of Lectin and Escherichia Coli

A water-soluble neutral fluorescent conjugated oligomer (FBT) is integrated with graphene oxide (GO) to form a hybrid nanoprobe with extremely low fluorescence background due to the robust quenching capability of GO. The contact between GO and FBT can be effectively shielded by Concanavalin A because of the strong specific protein-carbohydrate interaction, which ultimately allows light-up visual detection of lectin and Escherichia coli.

Semiconducting Polymer Nanoprobe for In Vivo Imaging of Reactive Oxygen and Nitrogen Species

Semiconducting polymer nanoparticles are utilized as a free-radical inert and light-harvesting nanoplatform for in vivo molecular imaging of reactive oxygen and nitrogen species (RONS). With its RONS-sensitive fluorescence, good biodistribution and passive targeting ability to leaky inflammatory vasculature, this nanoprobe permits detection of RONS in the microenvironment of spontaneous bacterial infection following systemic administration.

Semiconducting Polymer Nanobioconjugates for Targeted Photothermal Activation of Neurons

Optogenetics provides powerful means for precise control of neuronal activity; however, the requirement of transgenesis and the incapability to extend the neuron excitation window into the deep-tissue-penetrating near-infrared (NIR) region partially limit its application. We herein report a potential alternative approach to optogenetics using semiconducting polymer nanobioconjugates (SPNsbc) as the photothermal nanomodulator to control the thermosensitive ion channels in neurons. SPNsbc are designed to efficiently absorb the NIR light at 808 nm and have a photothermal conversion efficiency higher than that of gold nanorods. By virtue of the fast heating capability in conjunction with the precise targeting to the thermosensitive ion channel, SPNsbc can specifically and rapidly activate the intracellular Ca(2+) influx of neuronal cells in a reversible and safe manner. Our study provides an organic nanoparticle based strategy that eliminates the need for genetic transfection to remotely regulate cellular machinery.

Semiconducting Oligomer Nanoparticles as an Activatable Photoacoustic Probe with Amplified Brightness for In Vivo Imaging of pH

An activatable photoacoustic nanoprobe based on a semiconducting oligomer with amplified brightness and pH-sensing capability is developed by taking advantage of nanodoping to simultaneously create both intraparticle photoinduced electron transfer and intramolecular protonation within a single particle. This organic nanoprobe permits noninvasive real-time ratiometric photoacoustic imaging of pH in tumors in living mice through systemic administration at a relatively low dosage.

Optimizing the cationic conjugated polymer-sensitized fluorescent signal of dye labeled oligonucleotide for biosensor applications.

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.