Honors & Awards


  • Postdoctoral Fellowship, Susan G. Komen For The Cure (2012-1025)

Professional Education


  • Doctor of Philosophy, University of Toronto (2011)

Stanford Advisors


Journal Articles


  • Real-time imaging of oxidative and nitrosative stress in the liver of live animals for drug-toxicity testing NATURE BIOTECHNOLOGY Shuhendler, A. J., Pu, K., Cui, L., Uetrecht, J. P., Rao, J. 2014; 32 (4): 373-U240

    View details for DOI 10.1038/nbt.2838

    View details for Web of Science ID 000334340800022

  • Phosphorylcholine-coated semiconducting polymer nanoparticles as rapid and efficient labeling agents for in vivo cell tracking. Advanced healthcare materials Pu, K., Shuhendler, A. J., Valta, M. P., Cui, L., Saar, M., Peehl, D. M., Rao, J. 2014; 3 (8): 1292-1298

    Abstract

    Despite the pressing need to noninvasively monitor transplanted cells in vivo with fluorescence imaging, desirable fluorescent agents with rapid labeling capability, durable brightness, and ideal biocompatibility remain lacking. Here, phosphorylcholine-coated near-infrared (NIR) fluorescent semiconducting polymer nanoparticles (SPNs) are reported as a new class of rapid, efficient, and cytocompatible labeling nanoagents for in vivo cell tracking. The phosphorylcholine coating results in efficient and rapid endocytosis and allows the SPN to enter cells within 0.5 h in complete culture medium apparently independent of the cell type, while its NIR fluorescence leads to a tissue penetration depth of 0.5 cm. In comparison to quantum dots and Cy5.5, the SPN is tolerant to physiologically ubiquitous reactive oxygen species (ROS), resulting in durable fluorescence both in vitro and in vivo. These desirable physical and physiological properties of the SPN permit cell tracking of human renal cell carcinoma (RCC) cells in living mice at a lower limit of detection of 10 000 cells with no obvious alteration of cell phenotype after 12 d. SPNs thus can provide unique opportunities for optimizing cellular therapy and deciphering pathological processes as a cell tracking label.

    View details for DOI 10.1002/adhm.201300534

    View details for PubMedID 24668903

  • Bioorthogonal cyclization-mediated in situ self-assembly of small-molecule probes for imaging caspase activity in vivo NATURE CHEMISTRY Ye, D., Shuhendler, A. J., Cui, L., Tong, L., Tee, S. S., Tikhomirov, G., Felsher, D. W., Rao, J. 2014; 6 (6): 519-526

    Abstract

    Directed self-assembly of small molecules in living systems could enable a myriad of applications in biology and medicine, and already this has been used widely to synthesize supramolecules and nano/microstructures in solution and in living cells. However, controlling the self-assembly of synthetic small molecules in living animals is challenging because of the complex and dynamic in vivo physiological environment. Here we employ an optimized first-order bioorthogonal cyclization reaction to control the self-assembly of a fluorescent small molecule, and demonstrate its in vivo applicability by imaging caspase-3/7 activity in human tumour xenograft mouse models of chemotherapy. The fluorescent nanoparticles assembled in situ were imaged successfully in both apoptotic cells and tumour tissues using three-dimensional structured illumination microscopy. This strategy combines the advantages offered by small molecules with those of nanomaterials and should find widespread use for non-invasive imaging of enzyme activity in vivo.

    View details for DOI 10.1038/NCHEM.1920

    View details for Web of Science ID 000336897800014

  • Semiconducting polymer nanoparticles as photoacoustic molecular imaging probes in living mice NATURE NANOTECHNOLOGY Pu, K., Shuhendler, A. J., Jokerst, J. V., Mei, J., Gambhir, S. S., Bao, Z., Rao, J. 2014; 9 (3): 233-239

    Abstract

    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

  • Caspase-responsive smart gadolinium-based contrast agent for magnetic resonance imaging of drug-induced apoptosis CHEMICAL SCIENCE Ye, D., Shuhendler, A. J., Pandit, P., Brewer, K. D., Tee, S. S., Cui, L., Tikhomirov, G., Rutt, B., Rao, J. 2014; 5 (10): 3845-3852

    View details for DOI 10.1039/c4sc01392a

    View details for Web of Science ID 000341195100020

  • Positron Emission Tomography Imaging of Drug-Induced Tumor Apoptosis with a Caspase-Triggered Nanoaggregation Probe ANGEWANDTE CHEMIE-INTERNATIONAL EDITION Shen, B., Jeon, J., Palner, M., Ye, D., Shuhendler, A., Chin, F. T., Rao, J. 2013; 52 (40): 10511-10514

    Abstract

    Drug Design: An (18) F-labeled caspase-3-sensitive nanoaggregation positron emission tomography tracer was prepared and evaluated for imaging the caspase-3 activity in doxorubicin-treated tumor xenografts. Enhanced retention of the (18) F activity in apoptotic tumors is achieved through intramolecular macrocyclization and in situ aggregation upon caspase-3 activation.

    View details for DOI 10.1002/anie.201303422

    View details for Web of Science ID 000325091500023

  • Semiconducting Polymer Nanoprobe for In Vivo Imaging of Reactive Oxygen and Nitrogen Species ANGEWANDTE CHEMIE-INTERNATIONAL EDITION Pu, K., Shuhendler, A. J., Rao, J. 2013; 52 (39): 10325-10329

    Abstract

    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

  • Self-luminescing BRET-FRET near-infrared dots for in vivo lymph-node mapping and tumour imaging NATURE COMMUNICATIONS Xiong, L., Shuhendler, A. J., Rao, J. 2012; 3

    Abstract

    Strong autofluorescence from living tissues, and the scattering and absorption of short-wavelength light in living tissues, significantly reduce sensitivity of in vivo fluorescence imaging. These issues can be tackled by using imaging probes that emit in the near-infrared wavelength range. Here we describe self-luminescing near-infrared-emitting nanoparticles employing an energy transfer relay that integrates bioluminescence resonance energy transfer and fluorescence resonance energy transfer, enabling in vivo near-infrared imaging without external light excitation. Nanoparticles were 30-40?nm in diameter, contained no toxic metals, exhibited long circulation time and high serum stability, and produced strong near-infrared emission. Using these nanoparticles, we successfully imaged lymphatic networks and vasculature of xenografted tumours in living mice. The self-luminescing feature provided excellent tumour-to-background ratio (>100) for imaging very small tumours (2-3?mm in diameter). Our results demonstrate that these new nanoparticles are well suited to in vivo imaging applications such as lymph-node mapping and cancer imaging.

    View details for DOI 10.1038/ncomms2197

    View details for Web of Science ID 000315992100028

    View details for PubMedID 23149738