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1.  Enzyme-Directed Assembly of Nanoparticles in Tumors Monitored by In Vivo Whole Animal and Ex Vivo Super Resolution Fluorescence Imaging 
Journal of the American Chemical Society  2013;135(50):18710-18713.
Matrix metalloproteinase enzymes, overexpressed in HT-1080 human fibrocarcinoma tumors, were used to guide the accumulation and retention of an enzyme-responsive nanoparticle in a xenograft mouse model. The nanoparticles were prepared as micelles from amphiphilic block copolymers bearing a simple hydrophobic block, and a hydrophilic peptide brush. The polymers were end-labeled with Alexa Fluor 647 dyes leading to the formation of labeled micelles upon dialysis of the polymers from DMSO to aqueous buffer. This dye-labeling strategy allowed the presence of the retained material to be visualized via whole animal imaging in vivo, and in ex vivo organ analysis following intratumoral injection into HT-1080 xenograft tumors. We propose that the material is retained by virtue of an enzyme-induced accumulation process whereby particles change morphology from 20 nm spherical micelles to micron-scale aggregates, kinetically trapping them within the tumor. This hypothesis is tested here via an unprecedented super resolution fluorescence analysis of ex vivo tissue slices confirming a particle size increase occurs concomitantly with extended retention of responsive particles compared to unresponsive controls.
PMCID: PMC4021865  PMID: 24308273
2.  Phototrophic biofilm assembly in microbial-mat-derived unicyanobacterial consortia: model systems for the study of autotroph-heterotroph interactions 
Microbial autotroph-heterotroph interactions influence biogeochemical cycles on a global scale, but the diversity and complexity of natural systems and their intractability to in situ manipulation make it challenging to elucidate the principles governing these interactions. The study of assembling phototrophic biofilm communities provides a robust means to identify such interactions and evaluate their contributions to the recruitment and maintenance of phylogenetic and functional diversity over time. To examine primary succession in phototrophic communities, we isolated two unicyanobacterial consortia from the microbial mat in Hot Lake, Washington, characterizing the membership and metabolic function of each consortium. We then analyzed the spatial structures and quantified the community compositions of their assembling biofilms. The consortia retained the same suite of heterotrophic species, identified as abundant members of the mat and assigned to Alphaproteobacteria, Gammaproteobacteria, and Bacteroidetes. Autotroph growth rates dominated early in assembly, yielding to increasing heterotroph growth rates late in succession. The two consortia exhibited similar assembly patterns, with increasing relative abundances of members from Bacteroidetes and Alphaproteobacteria concurrent with decreasing relative abundances of those from Gammaproteobacteria. Despite these similarities at higher taxonomic levels, the relative abundances of individual heterotrophic species were substantially different in the developing consortial biofilms. This suggests that, although similar niches are created by the cyanobacterial metabolisms, the resulting webs of autotroph-heterotroph and heterotroph-heterotroph interactions are specific to each primary producer. The relative simplicity and tractability of the Hot Lake unicyanobacterial consortia make them useful model systems for deciphering interspecies interactions and assembly principles relevant to natural microbial communities.
PMCID: PMC3985010  PMID: 24778628
phototrophic biofilm model system; microbial diversity; primary succession; real-time PCR; community metabolomics; confocal microscopy; image analysis; microcosm
3.  Folate Receptor-Targeting Gold Nanoclusters as Fluorescence Enzyme Mimetic Nanoprobes for Tumor Molecular Colocalization Diagnosis 
Theranostics  2014;4(2):142-153.
Nanoprobes with enzyme-like properties attracted a growing interest in early screening and diagnosis of cancer. To achieve high accuracy and specificity of tumor detection, the design and preparation of enzyme mimetic nanoprobes with high enzyme activity, tumor targeting and excellent luminescence property is highly desirable. Herein, we described a novel kind of fluorescence enzyme mimetic nanoprobe based on folate receptor-targeting Au nanoclusters. The nanoprobes exhibited excellent stability, low cytotoxicity, high fluorescence and enzyme activity. We demonstrated that the nanoprobes could be used for tumor tissues fluorescence/visualizing detection. For the same tumor tissue slice, the nanoprobes peroxidase staining and fluorescent staining were obtained simultaneously, and the results were mutually complementary. Therefore, the fluorescence enzyme mimetic nanoprobes could provide a molecular colocalization diagnosis strategy, efficiently avoid false-positive and false-negative results, and further improve the accuracy and specificity of cancer diagnoses. By examining different clinical samples, we demonstrated that the nanoprobes could distinguish efficiently cancerous cells from normal cells, and exhibit a clinical potential for cancer diagnosis.
PMCID: PMC3900799  PMID: 24465272
Gold Nanoclusters; Fluorescence; Enzyme Mimetic; Tumor Diagnosis; Molecular Colocalization
4.  Video-assisted thoracic surgery right sleeve lobectomy 
Journal of Thoracic Disease  2013;5(Suppl 3):S323-S324.
PMCID: PMC3771627  PMID: 24040557
5.  Highly luminescent near-infrared-emitting gold nanoclusters with further natural etching: photoluminescence and Hg2+ detection 
Nanoscale Research Letters  2012;7(1):348.
Highly luminescent near-infrared (NIR)-emitting gold nanoclusters (Au NCs) protected by glutathione with ultra-small size were prepared at high temperature following with a further natural etching at room temperature. The optical and surface properties of Au NCs were monitored by ultraviolet–visible and photoluminescence (PL) spectra, high-resolution transmission electron microscopy, and electrospray ionization mass spectrometry. The diameter of the etched Au NCs was reduced to approximately 1.35 nm with 30 % PL quantum yield. Interestingly, the PL of Au NCs was decreased obviously by the addition of Hg2+ and increased by the addition of Pb2+ at certain concentration. Our preliminary results illustrated that the highly luminescent NIR-emitting Au NCs would be an alternative probe for the detection of heavy metal ions in water and environmental monitoring.
PMCID: PMC3570373  PMID: 22738180
Near-infrared-emitting gold nanoclusters; Natural etching; Highly luminescent; Hg2+; detection
6.  Optical sensing nanostructures for porous silicon rugate filters 
Porous silicon rugate filters [PSRFs] and combination PSRFs [C-PSRFs] are emerging as interesting sensing materials due to their specific nanostructures and superior optical properties. In this work, we present a systematic study of the PSRF fabrication and its nanostructure/optical characterization. Various PSRF chips were produced with resonance peaks that are adjustable from visible region to near-infrared region by simply increasing the periods of sine currents in a programmed electrochemical etching method. A regression analysis revealed a perfect linear correlation between the resonant peak wavelength and the period of etching current. By coupling the sine currents with several different periods, C-PSRFs were produced with defined multiple resonance peaks located at desired positions. A scanning electron microscope and a microfiber spectrophotometer were employed to analyze their physical structure and feature spectra, respectively. The sensing properties of C-PSRFs were investigated in an ethanol vapor, where the red shifts of the C-PSRF peaks had a good linear relationship with a certain concentration of ethanol vapor. As the concentration increased, the slope of the regression line also increased. The C-PSRF sensors indicated the high sensitivity, quick response, perfect durability, reproducibility, and versatility in other organic gas sensing.
PMCID: PMC3275543  PMID: 22252301
7.  Delivery of MicroRNA-10b with Polylysine Nanoparticles for Inhibition of Breast Cancer Cell Wound Healing 
Recent studies revealed that micro RNA-10b (mir-10b) is highly expressed in metastatic breast cancer cells and positively regulates breast cancer cell migration and invasion through inhibition of HOXD10 target synthesis. In this study we designed anti-mir-10b molecules and combined them with poly L-lysine (PLL) to test the delivery effectiveness. An RNA molecule sequence exactly matching the mature mir-10b minor antisense showed strong inhibition when mixed with PLL in a wound-healing assay with human breast cell line MDA-MB-231. The resulting PLL-RNA nanoparticles delivered the anti-microRNA molecules into cytoplasm of breast cancer cells in a concentration-dependent manner that displayed sustainable effectiveness.
PMCID: PMC3256732  PMID: 22259248
microRNA-10b; breast cancer metastasis; nanoparticles
8.  Nanometer resolution imaging by single molecule switching 
Nano Reviews  2010;1:10.3402/nano.v1i0.5122.
PMCID: PMC3215205  PMID: 22110849
9.  Photoswitchable Nanoparticles Enable High-Resolution Cell Imaging: The PULSAR Microscopy 
Journal of the American Chemical Society  2008;130(46):15279-15281.
Beyond-diffraction-limit optical imaging of cells will reveal biological mechanisms, cellular structures, and physiological processes in nanometer scale. Harnessing the photoswitching properties of spiropyran fluorophores, we achieved nano-resolution fluorescence imaging using photo-actuated unimolecular logical switching attained reconstruction (PULSAR) microscopy. The PULSAR microscope successfully resolved nanostructures and subcellular organelles when the photoswitchable nanoparticles containing spiropyran dyes were used as the fluorescent probes.
PMCID: PMC2651006  PMID: 18939833

Results 1-9 (9)