Honors & Awards
Postdoctoral Fellowship, Susan G. Komen For The Cure (2012-1025)
Doctor of Philosophy, University of Toronto (2011)
Jianghong Rao, Postdoctoral Faculty Sponsor
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
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
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
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 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
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