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Proceedings Volume 8233, including the Title Page, Copyright
information, Table of Contents, and the Conference Committee listing.
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Anti-VEGF therapies have been widely explored for the management of posterior ocular disease, like neovascular
age-related macular degeneration (AMD). Loading anti-VEGF therapies in biodegradable microparticles may enable
sustained drug release and improved therapeutic outcome. However, existing microfabrication processes such as double
emulsification produce drug-loaded microparticles with low encapsulation rate and poor antibody bioactivity. To
overcome these limitations, we fabricate multifunctional microparticles by both single needle and coaxial needle
electrospray. The experimental setup for the process includes flat-end syringe needles (both single needle and coaxial
needle), high voltage power supplies, and syringe pumps. Microparticles are formed by an electrical field between the
needles and the ground electrode. Droplet size and morphology are controlled by multiple process parameters and
material properties, such as flow rate and applied voltage. The droplets are collected and freezing dried to obtain
multifunctional microparticles. Fluorescent beads encapsulated poly(DL-lactide-co-glycolide) acid (PLGA)
microparticles are injected into rabbits eyes through intravitreal injection to test the biodegradable time of microparticles.
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Cancer therapy utilizing Molecular Layer Deposition (MLD) and Self-Organized Lightwave Network (SOLNET) is
proposed. MLD is a growth method, in which different kinds of molecules are sequentially provided to a substrate to
synthesize organic tailored materials with designated molecular arrangements. In cancer therapy, the liquid-phase MLD
(LP-MLD) is used with regarding the human body as the MLD chamber and the cancer cells as the substrates.
The first proposal is the selective delivery of multi-functional materials with imaging, sensitizing, paramagnetic, lightabsorbing
agents etc. to cancer cells by LP-MLD. The second proposal is in-situ synthesis of drugs, especially large and
toxic ones, at cancer cells by LP-MLD to deliver the drugs deep inside the cancer without attacking normal cells. The
third proposal is the SOLNET-assisted laser surgery. After luminescent molecules are adsorbed in cancer cells by LPMLD,
a write beam is introduced from an optical fiber into the area containing cancer cells through photo-induced
refractive index increase materials to construct self-aligned optical waveguides of SOLNET, which selectively guides
surgery beams to cancer cells. Theoretical predictions and preliminary experimental results are presented.
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Near-Infrared (NIR) dyes are used as reporters, probes or markers in the biological and medical field. NIR dyes can be
useful for investigating and characterizing biomolecular interactions or imaging which is possible because biological
mammalian tissue has a low absorption window in the NIR region. Biomolecules such as proteins are known to bind to
NIR dyes. Upon binding NIR dyes often exhibit spectral changes that can be used for characterizing the binding event.
Serum albumins may be responsible for in vivo transport of NIR dyes. Studying this binding event can be useful when
correlated to in vivo behavior of the NIR dye. The studies presented here use spectroscopic methods to investigate how
NIR dyes that may be used in imaging, biological or bioanalytical applications bind to proteins, such as serum albumins.
Our research group systematically synthesized several NIR dyes that have varying hydrophobicity, chromophore size
and charge. During these investigations we developed novel NIR cyanine fluorophores having varying aqueous
solubility and a variety of net charges. The binding properties of the carbocyanines change when charged or hydrophobic
moieties are systematically varied. One of the properties we put a special emphasis on is what we call residual hydrophobicity of the NIR dye molecule which is defined as the unmasked (by the charged moieties) hydrophobicity of the molecule. Residual hydrophobicity may be responsible for binding the otherwise highly water soluble NIR dye to hydrophobic pockets of biomolecules. High residual hydrophobicity of a highly water soluble dye can be disadvantageous during biological, medical or similar applications.
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Fluorescent dyes are the basis for a broad range of modern techniques in life and material sciences. Consequently, there
is a pressing need for the development of new classes of NIR fluorophores in recent years. Pyrrolopyrrole Cyanines
(PPCys) are a novel class of NIR chromophores that were first presented in 2007 by Fischer and coworkers.[1] Their
optical properties are marked by strong and narrowband NIR absorptions, strong NIR fluorescence and hardly any
absorption in the visible range. The absorption maxima can be tuned over a broad range while high fluorescence
quantum yields are maintained. PPCys are attractive candidates for labelling applications or as selective NIR absorbers.
Moreover, PPCys exhibit very high photostability. Due to these outstanding photophysical properties, PPCys are heading
into a promising future as NIR dyes.
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Excited state prototropism (ESPT) is observed in molecules having one or more ionizable protons, whose proton
transfer efficiency is different in ground and excited states. The interaction of various ESPT molecules like naphthols
and intramolecular ESPT (ESIPT) molecules like hydroxyflavones etc. with different microheterogeneous media have
been studied in detail and excited state prototropism as a probe concept has been gaining ground. The fluorescence of
different prototropic forms of such molecules, on partitioning to an organized medium like lipid bilayer membrane,
often show sensitive response to the local environment with respect to the local structure, physical properties and
dynamics. Our recent work using 1-naphthol as an ESPT fluorescent molecular probe has shown that the incorporation
of monomeric bile salt molecules into lipid bilayer membranes composed from dipalmitoylphosphatidylcholine (DPPC,
a lung surfactant) and dimyristoylphosphatidylcholine (DMPC), in solid gel and liquid crystalline phases, induce
appreciable wetting of the bilayer up to the hydrocarbon core region, even at very low (≤ 1 mM) concentrations of the
bile salts. The incorporation and location of fisetin, an ESIPT molecule having antioxidant properties, in lipid bilayer
membrane has been sensitively monitored from its intrinsic fluorescence behaviour.
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We have recently reported that a red-emitting iridium complex (btp)2 Ir (acac) (BTP) serves as a hypoxia-sensing
probe for tumor imaging in living mice. BTP exhibits oxygen-sensitive phosphorescence that can be utilized to
monitor oxygen levels in living cells and to visualize hypoxic tissues. To improve the tissue penetrance of BTP, we
designed and synthesized near-IR emitting iridium complexes by two different approaches: extension of the π-
conjugated system of benzothienyl-pyridinato ligand in BTP and introduction of substituents into suitable
positions of ligands. The former approach was successful, and near-IR emitting iridium complexes were obtained
without reduction in the emission quantum yield. Cellular uptake of BTP was greatly improved by introducing a
hydrophilic group into the acetylacetonato ligand. Using these improved probes, in-vivo lifetime measurements
were made to substantiate the hypoxia of tumor tissues in SCC-7 tumor-bearing mice. The second-harmonic (532 nm) of Nd3+:YAG laser was used to excite iridium complexes in tissues, and the phosphorescence lifetime was measured using the time-correlated single photon counting technique. The phosphorescence emitted from the tumor region actually gave longer lifetimes compared to those emitted from the normal tissues, demonstrating the hypoxic nature of tumor tissues.
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Rajiv Abhyankar, Banakanidhi Sahoo, Niraj K. Singh, Linda M. Meijer, Bidyut Sarkar, Anand K. Das, Suman Nag, Muralidharan Chandrakesan, Debanjan Bhowmik, et al.
Proceedings Volume Reporters, Markers, Dyes, Nanoparticles, and Molecular Probes for Biomedical Applications IV, 82330B (2012) https://doi.org/10.1117/12.909829
While dozens of human ailments are now identified as "protein aggregation diseases", aggregation by itself does not
seem to be a clear determinant of the toxicity. The structural transformation that accompanies the initial steps of
aggregation may be an even more important aspect controlling the biological effects of these protein particles. For this,
the key is to develop appropriate fluorescent biomarkers which can probe both aggregation and conformation at low
physiological concentrations. Using Alzheimer's amyloid beta (Aβ) as a model system, we have developed probes
suitable for the application of Fluorescence Correlation Spectroscopy (FCS, which reports aggregation) and Förster
Resonance Energy Transfer (FRET, which reports conformational changes) techniques. To diagnose these changes in
the cerebrospinal fluid of Alzheimer's patients, we are now designing better single molecule detection devices. Here we
report a confocal device with a 4π collection geometry, which detects more than 0.5 million photons per second from a
single rhodamine B molecule in aqueous solution, which to our knowledge is the highest sensitivity achieved so far
with such devices. This allows us to perform quick and sensitive antibunching measurements which report the
aggregate mass and fluorophore lifetime of Aβ oligomers.
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Quench-based probes utilize unique characteristics of fluorescence resonance energy transfer (FRET) to enhance contrast
upon de-quenching. This mechanism has been used in a variety of molecular probes for imaging of cancer related
enzyme activity such as matrix metalloproteinases, cathepsins and caspases. While non-fluorescent upon administration,
fluorescence can be restored by separation of donor and acceptor, resulting in higher intensity in the presence of
activator. Along with decreased quantum yield, FRET also results in altered fluorescence lifetime. Time-domain imaging
can further enhance contrast and information yield from quench-based probes. We present in vivo time-domain imaging
for detecting activation of quench-based probes.
Quench-based probes utilize unique characteristics of fluorescence resonance energy transfer (FRET) to enhance contrast
upon de-quenching. This mechanism has been used in a variety of molecular probes for imaging of cancer related
enzyme activity such as matrix metalloproteinases, cathepsins and caspases. While non-fluorescent upon administration,
fluorescence can be restored by separation of donor and acceptor, resulting in higher intensity in the presence of
activator. Along with decreased quantum yield, FRET also results in altered fluorescence lifetime. Time-domain imaging
can further enhance contrast and information yield from quench-based probes. We present in vivo time-domain imaging
for detecting activation of quench-based probes. Time-domain diffuse optical imaging was performed to assess the FRET
and quenching in living mice with orthotopic breast cancer. Tumor contrast enhancement was accompanied by increased
fluorescence lifetime after administration of quenched probes selective for matrix metalloproteinases while no significant
change was observed for non-quenched probes for integrin receptors. These results demonstrate the utility of timedomain
imaging for detection of cancer-related enzyme activity in vivo.
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Imaging Molecular Processes with Fluorescent Reporters
We recently reported construction of a new type of optical nano-construct composed of genome-depleted plant infecting
brome mosaic virus (BMV) doped with Indocyanine green (ICG), an FDA-approved chromophore. We refer to these
constructs as optical viral ghosts (OVGs) since only the capsid protein (CP) subunits of BMV remain to encapsulate
ICG. To utilize OVGs as effective nano-probes in fluorescence imaging applications, their fluorescence quantum yield
needs to be maximized. In this study, we investigate the effect of altering the CP to ICG mass ratio on the fluorescent
quantum yield of OVGs. Results of this study provide the basis for construction of OVGs with optimal amounts of CP
and ICG to yield maximal fluorescence quantum yield.
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B. anthracis is a gram-positive, spore-forming bacterium which likes all pathogenic bacteria, survive by sequestering
heme from its host. To image B. anthracis heme catabolism in vivo, we stably transfect new red excitable fluorescent
protein, IFP1.4, that requires the heme catabolism product biliverdin (BV). IFP1.4 reporter has favorable excitation and
emission characteristics, which has an absorption peak at 685 nm and an emission peak at 708 nm. Therefore, IFP1.4
reporter can be imaged deeply into the tissue with less contamination from tissue autofluorescence. However, the
excitation light "leakage" through optical filters can limit detection and sensitivity of IFP1.4 reporter due to the small
Stoke's shift of IFP1.4 fluorescence. To minimize the excitation light leakage, an intensified CCD (ICCD) based
infrared fluorescence imaging device was optimized using two band pass filters separated by a focus lens to increase the
optical density at the excitation wavelength. In this study, a mouse model (DBA/J2) was first injected with B. anthracis
bacteria expressing IFP1.4, 150 μl s.c., on the ventral side of the left thigh. Then mouse was given 250 μl of a 1mM BV
solution via I.V. injection. Imaging was conducted as a function of time after infection under light euthanasia, excised
tissues were imaged and IFP1.4 fluorescence correlated with standard culture measurements of colony forming units
(CFU). The work demonstrates the use of IFP1.4 as a reporter of bacterial utilization of host heme and may provide an
important tool for understanding the pathogenesis of bacterial infection and developing new anti-bacterial therapeutics.
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Targeted delivery of therapeutic and imaging agents using surface modified nanovectors has been explored immensely in
recent years. The growing demand for site-specific and efficient delivery of nanovectors entails stable surface
conjugation of targeting moieties. We have developed a polymeric nanocapsule doped with Indocyanine green (ICG)
with potential for targeted and deep tissue optical imaging and phototherapy. Our ICG-loaded nanocapsules (ICG-NCs)
have potential for covalent coupling of various targeting moieties and materials due to presence of amine groups on the
surface. Here, we covalently bioconjugate polyethylene glycol(PEG)-coated ICG-NCs with monoclonal antibody against
HER2 through reductive amination-mediated procedures. The irreversible and stable bonds are formed between anti-
EGFR and aldehyde termini of PEG chains on the surface of ICG-NCs. We confirm the uptake of conjugated ICG-NCs
by ovarian cancer cells over-expressing HER2 using fluorescent confocal microscopy. The proposed process for
covalent attachment of anti-HER2 to PEGylated ICG-NCs can be used as a methodology for bioconjugation of various
antibodies to such nano-constrcuts, and provides the capability to use these optically active nano-probes for targeted
optical imaging of ovarian and other cancer types.
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The understanding of the interaction between tumors and surrounding microenvironment in vivo is an important first step
and basis for pathway-targeting cancer therapy. To in vivo observe the dynamic development of tumor cells and validate
the efficacy of therapy in microscopic scales, people commonly performed multi-photon fluorescence microscopy
through an invasive window chamber setup. However, under such system, the cancer cells can't be identified and
long-term tracked without a fluorescence labeling. Exploiting the intrinsic third harmonic generation (THG) and
two-photon fluorescence (2PF) contrasts of melanin, we demonstrated in vivo identification of melanoma and tracked its
development without labeling. It was achieved with a least invasive femtosecond Cr:forsterite laser and a laser scanning
nonlinear microscopy system with 3D sub-micron spatial resolution. Combined with molecular probes or reporters, we
anticipate thus developed platform a powerful tool to reveal molecular insights of tumor microenvironments, enhance
our understanding of tumor biology, and trigger new therapeutic approaches.
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To investigate whether endogenous biliverdins can serve as a fluorescence metabolic marker in cancer diagnosis, we
measured their multiphoton fluorescence spectra and lifetimes with femtosecond Cr:forsterite laser. Excited at 1230nm,
the two-photon fluorescence of biliverdins peaks around 670nm. The corresponding lifetime (<100ps) was much shorter
than those of porphyrins (~10ns), which is another commonly present metabolites in living cells. Further mixing
biliverdins with proteins like fetal bovine serum (FBS), biliverdins reductase A (BVRA), or heme oxygenase-1 (HO-1),
the yields of red autofluorescences didn't change a lot, but the corresponding lifetimes with HO-1 and BSA were
lengthened to 200~300ps. This indicates that biliverdin can have an association with these proteins and change its
lifetime. These spectral and temporal characteristics of fluorescence make biliverdin a potential marker fluorophore for
hyperspectral diagnosis on the heme catabolism in human cells or tissues.
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The present work explores the feasibility of using surface enhanced Raman scattering (SERS) for detecting the
neurotransmitters such as glutamate (GLU) and gamma-amino butyric acid (GABA). These amino acid neurotransmitters
that respectively mediate fast excitatory and inhibitory neurotransmission in the brain, are important for neuroendocrine
control, and upsets in their synthesis are also linked to epilepsy. Our SERS-based detection scheme enabled the detection
of low amounts of GLU (10-7 M) and GABA (10-4 M). It may complement existing techniques for characterizing such
kinds of neurotransmitters that include high-performance liquid chromatography (HPLC) or mass spectrography (MS).
This is mainly because SERS has other advantages such as ease of sample preparation, molecular specificity and
sensitivity, thus making it potentially applicable to characterization of experimental brain extracts or clinical diagnostic samples of cerebrospinal fluid and saliva. Using hollow core photonic crystal fiber (HC-PCF) further enhanced the
Raman signal relative to that in a standard cuvette providing sensitive detection of GLU and GABA in micro-litre
volume of aqueous solutions.
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Enhanced permeability and retention (EPR) effects for tumor treatment have been utilized as a representative strategy to
accumulate untargeted nanoparticles in the blood vessels around tumors. However, the EPR effect itself was not
sufficient for the nanoparticles to penetrate into cancer cells. For the improvement of diagnosis and treatment of cancer
using nanoparticles, many more nanoparticles need to specifically enter cancer cells. Otherwise, can leave the tumor
area and not contribute to treatment. In order to enhance the internalization process, specific ligands on nanoparticles
can help their specific internalization in cancer cells by receptor-mediated endocytosis. We previously developed glycol
chitosan based nanoparticles that suggested a promising possibility for in vivo tumor imaging using the EPR effect. The
glycol chitosan nanoparticles showed a long circulation time beyond 1 day and they were accumulated predominantly in
tumor. In this study, we evaluated two peptides for specific targeting and better internalization into urinary bladder
cancer cells. We conjugated the peptides on to the glycol chitosan nanoparticles; the peptide-conjugated nanoparticles
were also labeling with near infrared fluorescent (NIRF) dye, Cy5.5, to visualize them by optical imaging in vivo.
Importantly real-time NIRF imaging can also be used for fluorescence (NIRF)-guided surgery of tumors beyond normal
optical penetration depths. The peptide conjugated glycol chitosan nanoparticles were characterized with respect to size,
stability and zeta-potential and compared with previous nanoparticles without ligands in terms of their internalization
into bladder cancer cells. This study demonstrated the possibility of our nanoparticles for tumor imaging and
emphasized the importance of specific targeting peptides.
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We recently reported the construction of a new type of optically active nano-particles composed of genome-depleted
plant infecting brome mosaic virus (BMV) doped with indocyanine green (ICG), an FDA-approved chromophore . We
refer to these constructs as optical viral ghosts (OVGs) since only the capsid protein (CP) subunits of BMV remain to
encapsulate ICG. Herein, we covalently conjugated the surface of OVGs with anti-epidermal growth factor receptors
(anti-EGFR) to target cancerous human bronchial epithelial cells (C-HBECs) in-vitro. Our preliminary results demonstrate the utility of conjugated OVGs for targeted imaging of cancer cells.
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The purpose of this study was to develop targeted polymeric magnetic nanoparticle system for brain imaging. Near
infrared dye indocyanine green (ICG) or p-gycoprotein substrate rhodamine 123 (Rh123) were encapsulated along with
oleic acid coated magnetic nanoparticles (OAMNP) in a matrix of poly(lactide-co-glycolide) (PLGA) and methoxy
poly(ethyleneglycol)-poly(lactide) (Met-PEG-PLA). The nanoparticles were evaluated for morphology, particle size, dye
content and magnetite content. The in vivo biodistribution study was carried out using three groups of six male Sprague
Dawley rats each. Group I received a saline solution containing the dye, group II received dye-loaded polymeric magnetic
nanoparticles without the aid of a magnetic field, and group III received dye-loaded polymeric magnetic nanoparticles
with a magnet (8000 G) placed on the head of the rat. After a preset exposure period, the animals were sacrificed and dye
concentration was measured in the brain, liver, kidney, lungs and spleen homogenates. Brain sections were fixed,
cryotomed and visualized using fluorescence microscopy. The particles were observed to be spherical and had a mean
size of 220 nm. The encapsulation efficiency for OAMNP was 57%, while that for ICG was 56% and for Rh123 was
45%. In the biodistribution study, while the majority of the dose for all animals was found in the liver, kidneys and
spleen, group III showed a significantly higher brain concentration than the other two groups (p < 0.001). This result was
corroborated by the fluorescence microscopy studies, which showed enhanced dye penetration into the brain tissue for
group III. Further studies need to be done to elucidate the exact mechanism responsible for the increased brain uptake of
dye to help us understand if the magnetic nanoparticles actually penetrate the blood brain barrier or merely deliver a
massive load of dye just outside it, thereby triggering passive diffusion into the brain parenchyma. These results reinforce
the potential use of polymeric magnetically-targeted nanoparticles in active brain targeting and imaging.
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Natriuretic peptides (NPs) are clinical markers of heart disease that have anti-proliferative and anti-migratory effects on
vascular smooth-muscle cells (VSMCs). In atherosclerosis, NPs participate in vascular remodeling, where the expression
of NP clearance receptors (NPR-Cs) is upregulated both in the endothelium and in VSMCs[1-3]. In this study, we
investigated the enhanced targeting potential of novel multifunctional nanoprobes conjugated with multiple copies of a
C-type atrial natriuretic factor (C-ANF) peptide fragment to target NPR-C transfected cells. The cell binding results of
the NPR-C targeted nanoprobes were compared with that of the C-ANF peptide fragment alone. The nanoprobe and
peptide structures contain the chelator DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) for labeling
with the PET tracer, 64Cu, for radioactive assays and luminescent Eu (III) for confocal cell imaging. Cell assays
performed with the radioactive nanoprobe and peptide demonstrated higher cell binding of the targeted nanoprobe
comapred with the peptide alone (8.63±1.67 vs. 1.13±0.06). The targeting specificity of both moieties was tested by using the control cell lines NPR-A and NPR-B, and receptor mediated uptake was demonstrated by reduced uptake in the presence of excess unlabeled respective probes.
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Gold nanoshells with NIR plasmon resonance can be modified to simultaneously enhance conjugated NIR
fluorescence dyes and T2 contrast of embedded iron-oxide nanoparticles, and molecularly targeted to breast and other
cancers. We calibrated the theranostic performance of magneto-fluorescent nanoshells, and contrasted the performance
of molecularly targeted and untargeted nanoshells for breast cancer therapy, employing MCF-7L and their HER2 overexpressing
derivative MCF-7/HER2-18 breast cancer cells as in vitro model systems. Silica core gold nanoshells with
plasmon resonance on ~810 nm were doped with NIR dye ICG and ~10 nm iron-oxide nanoparticles in a ~20 nm epilayer
of silica. A subset of nanoshells was conjugated to antibodies targeting HER2. Cell viability with varying laser
power levels in presence and absence of bare and HER2-targeted nanoshells was assessed by calcein and propidium
iodide staining. For MCF-7L cells, increasing power resulted in increased cell death (F=5.63, p=0.0018), and bare
nanoshells caused more cell death than HER2-targeted nanoshells or laser treatment alone (F=30.13, p<0.001). For
MCF-7/HER2-18 cells, death was greater with HER2-targeted nanoshells and was independent of laser power. This
study demonstrates the capability of magneto-fluorescent nanocomplexes for imaging and therapy of breast cancer cells,
and the advantages of targeting receptors unique to cancer cells.
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Inorganic Nanoparticles for Biological Applications
New in vivo imaging reagents with increased sensitivity and penetration depth are needed to advance our understanding
of metastases and accelerate the development of therapeutics. The folate receptor (FR) is a promising imaging target that
is up-regulated in many human carcinomas, including cancers of the ovary, breast, pancreas, endometrium, lungs,
kidneys, colon, brain, and myeloid cells. Zymera has developed a self-illuminating Bioluminescence Resonance Energy
Transfer Quantum Dot (BRET-Qdot) nanoprobe conjugated with folate (BQ-Folate) for in vivo imaging of cancers overexpressing
FR. BQ-Folate is a novel nanoprobe formed by co-conjugating Renilla reniformis luciferase enzyme and
folate to near-infrared (NIR) emitting quantum dots. The luciferase substrate, coelenterazine, activates the BQ-Folate
nanoprobe generating luminescence emission in the near-infrared (NIR) region (655 nm) for increased sensitivity and
penetration depth. Because BQ-Folate requires no external light source for light emission, it has significant advantages
for challenging in vivo preclinical optical imaging applications, such as the detection of early stage metastases. Zymera
and OncoMed Pharmaceuticals have demonstrated that in vivo imaging with the BQ-Folate nanoprobe detected the
primary tumor and early stage metastases in an orthotopic NOD/SCID mouse model of human pancreatic cancer.
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Preclinical molecular imaging of cancer has the potential to increase the understanding of fundamental cancer biology,
elucidate mechanisms of cancer treatment resistance, and increase effectiveness of drug candidates. Optical and
magnetic resonance imaging contain complementary strengths, suitable for gaining a wealth of knowledge when
combined. Here, we demonstrate the inherent contrast sensitivity of single walled carbon nanotubes to absorption based
photothermal optical coherence tomography (PT-OCT), and magnetic resonance imaging spin dephasing contrast (T2).
A spectral-domain OCT system was interfaced with an amplitude-modulated (100 Hz) titanium sapphire pump beam for
PT-OCT imaging. MRI was performed with a commercial 4.7 T animal scanner. With both imaging tools, contrast
agent signal linearity (r2 > 0.95) and nM sensitivity over background (p < 0.05) was experimentally determined with
serially dilute solutions of carbon nanotubes coated in amine-terminated polyethylene glycol. The surface functionalization chemistry for carbon nanotubes is well understood, and molecular targeting has been demonstrated in vitro and in vivo, making carbon nanotubes an attractive agent for molecular imaging in preclinical models. We have demonstrated the initial characterization steps for using carbon nanotubes for multi-modality imaging with PT-OCT and MRI.
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The results of quantum-chemical analysis of elastic and strength properties of the bamboo-like tube are presented in this
paper. For the first time the configuration of the thinnest stable bamboo-like tube was established. The bamboo-like
nanotube breaking point is established to be under compression of 11GPa. Configuration of the nanoindentor based on
symmetric and streamlined tip of the tube (15,15), presented in this work, provides perfect interaction between the
nanoindentor tip and the tissue because tip has no sharp protruding pieces.
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Highly efficient upconverting phosphors (NaYF4) doped with erbium ions are bio-conjugated and used for cancer
imaging and photodynamic therapy. Once they are conjugated, the particles are injected into mice to demonstrate that
cancer imaging with a near-infrared excitation source is possible. Finally, the particles are also conjugated with a
photosensitive molecule with strong absorption near the upconversion emission peak (~ 550nm). The upconversion
energy causes the photosensitive molecule to create highly reactive oxidative species, which puncture and kill the cell to
which it is attached. These particles are then used in a mouse model, and the size of the tumors is modeled as a function
of the dosage and duration of the photodynamic therapy.
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The results of the theoretical investigation of the curvature influence of the strained graphene nanoribbon on its sensory
properties are presented in the given work. The attachment mechanisms of hydrogen atoms to the plane and the wavelike
graphene nanoribbon are studied by the tight-binding method. For the first time it was established, that the sensory
properties of nanoribbon improve with increase of the surface curvature. It was revealed, that the potential well depth of
interaction of the curved graphene with hydrogen atom is greater than the planar graphene. It was established, that the
difference of the potential minima of the C-H interaction energy increases exponentially with the curvature increase.
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New luminescent lanthanide chelates containing thiol-, amine-, and click-reactive groups in antenna-fluorophore
moieties were synthesized. The chelates include diethylenetriaminepentaacetic acid (DTPA) coupled to two types of
chromophores: 7-amino-4-trifluoromethyl-2(1H) quinolinone, and 7-amino-4-trifluoromethyl-2-alkoxyquinoline. The
synthesized compounds were characterized using NMR, light absorption, steady-state and time-resolved fluorescent
spectroscopy. Some of the compounds displayed high brightness with Tb3+, Eu3+, and Dy3+. Obtained reactive lanthanide
chelates can be easily attached to biological molecules. The probes demonstrated high performance in molecular beaconbased
DNA hybridization assays (sub-pico molar detection limit), in bacterial proteome labeling, and in live cell
imaging.
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Human serum albumin (HSA) plays an important role in the transport and disposition of endogenous and exogenous
ligands present in blood. Its capacity to reversibly bind a large variety of drugs results in its prevailing role in drug
pharmacokinetics and pharmacodynamics. In this work, we used 7-hydroxyquinoline (7HQ) as a probe to study the
binding nature of one of the major drug binding sites of HSA (Sudlow I) and to reveal the local environment around the
probe in the binding site. The interaction between 7HQ and HSA at a physiological pH of 7.2 was investigated using
steady-state and lifetime spectroscopic measurements, molecular docking and molecular dynamics (MD) simulations
methods. The fluorescence results indicate a selective interaction between 7HQ and the Trp214 residue. The reduction in
both the intensity and lifetime of the Trp214 fluorescence upon probe binding indicates the dominant role of static
quenching. Molecular docking and MD simulations show that 7HQ binds in Sudlow site I close to Trp214, confirming
the experimental results, and pinpoint the dominant role of hydrophobic interaction in the binding site. Electrostatic
interactions were also found to be important in which two water molecules form strong hydrogen bonds with the polar
groups of 7HQ. Detection of water in the binding site agrees with the absorption and fluorescence results that show the
formation of a zwitterion tautomer of 7HQ. The unique spectral signatures of 7HQ in water make this molecule a
potential probe for detecting the presence of water in nanocavities of proteins. Interaction of 7HQ with water in the
binding site shows that water molecules can be crucial for molecular recognition and association in protein binding sites.
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We report the results of the chitosan dimer study, the mechanism of its interaction with the carbon nanostructures and
also the mechanical properties of the chitosan/graphene, chitosan/nanotube complexes using the density function and
the molecular dynamic methods. It was established that the physical adsorption of the chitosan with graphene is carried
out by the Van der Waals interaction between the hexagonal links of the chitosan with the hexagonal cell of the atomic
grid of graphene and nanotube.
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Objective: To observe the differences of cell death and accumulation of reactive oxygen species (ROS) in the process of
infecting Arabidopsis with avirulent Pseudomonas syringae pv. tomato DC3000 (avrB, avrRps4), it will be of great
importance to research the role of plant disease resistance and defense response. Methods: Using WT, AtrbohD and
AtrbohF mutant as experimental materials, we discuss the impact of cell death and ROS on the leaves of Arabidopsis
infected with avirulent Pst DC3000 (avrB, avrRps4), observed by spectral analysis and visualized by DAB and trypan
blue stain. Results: When infected with avirulent Pst DC3000, both WT and AtrbohF mutant line behaved resistance that
exhibited burst of ROS and HR occur, limit senescence and pathogen induced chlorotic cell death. Paradoxically,
AtrbohD mutant behaved susceptible characters that exhibited a small quantity of ROS accumulated and enhanced cell
death. Conclusion: After infection of Arabidopsis with avirulent Pst DC3000, WT exhibited more ROS accumulation
than AtrbohF, and AtrbohD eliminated the majority of total ROS production. Although both WT and AtrbohF mutant
exhibited HR occur, enhanced cell death in AtrbohD mutant.
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Infection of plants with pathogens leads to programmed cell death (PCD) associated with the pathogen-triggered
hypersensitive response (HR) during plant innate immunity. In this study, the effects of infection by virulent
Pseudomonas syringae pv. tomato (Pst) DC3000 and strains harboring avirulence factors AvrRps4 on the induction of
HR-PCD were compared. We used Arabidopsis thaliana plants as materials, which expressed green fluorescent protein
labeled mitochondria (mito-GFP) and green fluorescent protein tagged ATG5 (ATG5-GFP), these GFP are instantaneous
expression. We found both Pst DC3000 and Pst-avrRps4 could induce mitochondria to assemble, the effect of Pst
DC3000 was more obvious. ATG5 was located in chloroplasts after infection with Pst DC3000 or Pst-avrRps4. Under
the condition of Pst-avrRps4, the expression of ATG5 was stronger than Pst DC3000 treatment.
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Fluorescent nanodiamonds (ND) provide advantageous properties as a fluorescent biomarker for in vitro and in
vivo studies. The maximum fluorescence occurs around 700 nm, they do not show photobleaching or blinking and
seem to be nontoxic. After a pretreatment with strong acid fluorescent ND can be functionalized and coupled to
endotoxin. Endotoxin is a decay product of bacteria and causes strong immune reactions. Therefore endotoxin
has to be removed for most applications. An effective removal procedure is membrane filtration. The endotoxin,
coupled to fluorescent ND can be visualized by using confocal microscopy which allows the investigation of the
separation mechanisms of the filtration process within the membranes.
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