13 research outputs found
Metabolomics based markers predict type 2 diabetes in a 14-year follow-up study
Chemical
probes are key components of the bioimaging toolbox, as
they label biomolecules in cells and tissues. The new challenge in
bioimaging is to design chemical probes for three-dimensional (3D)
tissue imaging. In this work, we discovered that light scattering
of metal nanoparticles can provide 3D imaging contrast in intact and
transparent tissues. The nanoparticles can act as a template for the
chemical growth of a metal layer to further enhance the scattering
signal. The use of chemically grown nanoparticles in whole tissues
can amplify the scattering to produce a 1.4 million-fold greater photon
yield than obtained using common fluorophores. These probes are non-photobleaching
and can be used alongside fluorophores without interference. We demonstrated
three distinct biomedical applications: (a) molecular imaging of blood
vessels, (b) tracking of nanodrug carriers in tumors, and (c) mapping
of lesions and immune cells in a multiple sclerosis mouse model. Our
strategy establishes a distinct yet complementary set of imaging probes
for understanding disease mechanisms in three dimensions
Parametric Study on Dimensional Control of ZnO Nanowalls and Nanowires by Electrochemical Deposition
A simple electrochemical deposition technique is used to synthesize both two-dimensional (nanowall) and one-dimensional (nanowire) ZnO nanostructures on indium-tin-oxide-coated glass substrates at 70°C. By fine-tuning the deposition conditions, particularly the initial Zn(NO3)2·6H2O electrolyte concentration, the mean ledge thickness of the nanowalls (50–100 nm) and the average diameter of the nanowires (50–120 nm) can be easily varied. The KCl supporting electrolyte used in the electrodeposition also has a pronounced effect on the formation of the nanowalls, due to the adsorption of Cl− ions on the preferred (0001) growth plane of ZnO and thereby redirecting growth on the (100) and (20) planes. Furthermore, evolution from the formation of ZnO nanowalls to formation of nanowires is observed as the KCl concentration is reduced in the electrolyte. The crystalline properties and growth directions of the as-synthesized ZnO nanostructures are studied in details by glancing-incidence X-ray diffraction and transmission electron microscopy
Make Nanomedicine Great Again ...... By Understanding Biological Barriers To Drug Delivery
Cancer targeting nanoparticles face a variety of biological environments between the site of injection and cancer cells. While researchers can measure the properties of nanoparticles outside the body, interactions with biological environment and its effect on nanoparticle tumour delivery remains unexplored. Understanding these barriers for cancer nanomedicine is the first step towards overcoming them. Here, I focus on three aspects of 3 nano-bio interactions enroute to cancer that dictates its biological fate: 1) Nanoparticle-Blood: Serum protein adsorption on circulating nanoparticles can be used as input to develop a supervised learning algorithm that can predict the fate of nanoparticles. This model achieved 77-95% accuracy in its prediction and altering the proteins on the surface led to reduction in liver and spleen uptake. 2) Nanoparticle – Tumour Blood Vessels: The dominant mechanism of nanoparticle entry into solid tumours is trans-endothelial and not through inter-endothelial gaps via Enhanced Permeation and Retention (EPR) effect. Upto 97% of nanoparticles were found to extravasate into the tumour via trans-endothelial pathways. This changes our approach to developing cancer nanomedicine as we now have to utilize this active mechanism instead of relying of passive accumulation. 3) Nanoparticle-Tumour: We have developed an approach that allows 3D imaging of nanoparticles in intact tumours. This technique is high throughput, cost effective and is compatible with both organic and inorganic nanoparticles. This is now allowing us to map all the barriers to cancer nanomedicine in tumours. This map is powerful because it forms the basis for classifying tumours into zones of varying nanoparticle distribution and can make accurate predictions of nanoparticle targeting efficiency. The work presented here arms the field of cancer nanomedicine with the biological barriers that need to be taken into design considerations to improve its clinical translation.Ph.D.2020-12-09 00:00:0
Exploring Passive Clearing for 3D Optical Imaging of Nanoparticles in Intact Tissues
The
three-dimensional (3D) optical imaging of nanoparticle distribution
within cells and tissues can provide insights into barriers to nanoparticle
transport in vivo. However, this approach requires the preparation
of optically transparent samples using harsh chemical and physical
methods, which can lead to a significant loss of nanoparticles and
decreased sensitivity of subsequent analyses. Here, we investigate
the influence of electrophoresis and clearing time on nanoparticle
retention within intact tissues and the impact of these factors on
the final 3D image quality. Our findings reveal that longer clearing
times lead to a loss of nanoparticles but improved transparency of
tissues. We discovered that passive clearing improved nanoparticle
retention 2-fold compared to results from electrophoretic clearing.
Using the passive clearing approach, we were able to observe a small
population of nanoparticles undergoing hepatobiliary clearance, which
could not be observed in liver tissues that were prepared by electrophoretic
clearing. This strategy enables researchers to visualize the interface
between nanomaterials and their surrounding biological environment
with high sensitivity, which enables quantitative and unbiased analysis
for guiding the next generation of nanomedicine designs
Three-Dimensional Optical Mapping of Nanoparticle Distribution in Intact Tissues
The
role of tissue architecture in mediating nanoparticle transport, targeting,
and biological effects is unknown due to the lack of tools for imaging
nanomaterials in whole organs. Here, we developed a rapid optical
mapping technique to image nanomaterials in intact organs <i>ex vivo</i> and in three-dimensions (3D). We engineered a high-throughput
electrophoretic flow device to simultaneously transform up to 48 tissues
into optically transparent structures, allowing subcellular imaging
of nanomaterials more than 1 mm deep into tissues which is 25-fold
greater than current techniques. A key finding is that nanomaterials
can be retained in the processed tissue by chemical cross-linking
of surface adsorbed serum proteins to the tissue matrix, which enables
nanomaterials to be imaged with respect to cells, blood vessels, and
other structures. We developed a computational algorithm to analyze
and quantitatively map nanomaterial distribution. This method can
be universally applied to visualize the distribution and interactions
of materials in whole tissues and animals including such applications
as the imaging of nanomaterials, tissue engineered constructs, and
biosensors within their intact biological environment
Three-Dimensional Imaging of Transparent Tissues via Metal Nanoparticle Labeling
Chemical
probes are key components of the bioimaging toolbox, as
they label biomolecules in cells and tissues. The new challenge in
bioimaging is to design chemical probes for three-dimensional (3D)
tissue imaging. In this work, we discovered that light scattering
of metal nanoparticles can provide 3D imaging contrast in intact and
transparent tissues. The nanoparticles can act as a template for the
chemical growth of a metal layer to further enhance the scattering
signal. The use of chemically grown nanoparticles in whole tissues
can amplify the scattering to produce a 1.4 million-fold greater photon
yield than obtained using common fluorophores. These probes are non-photobleaching
and can be used alongside fluorophores without interference. We demonstrated
three distinct biomedical applications: (a) molecular imaging of blood
vessels, (b) tracking of nanodrug carriers in tumors, and (c) mapping
of lesions and immune cells in a multiple sclerosis mouse model. Our
strategy establishes a distinct yet complementary set of imaging probes
for understanding disease mechanisms in three dimensions
Three-Dimensional Imaging of Transparent Tissues via Metal Nanoparticle Labeling
Chemical
probes are key components of the bioimaging toolbox, as
they label biomolecules in cells and tissues. The new challenge in
bioimaging is to design chemical probes for three-dimensional (3D)
tissue imaging. In this work, we discovered that light scattering
of metal nanoparticles can provide 3D imaging contrast in intact and
transparent tissues. The nanoparticles can act as a template for the
chemical growth of a metal layer to further enhance the scattering
signal. The use of chemically grown nanoparticles in whole tissues
can amplify the scattering to produce a 1.4 million-fold greater photon
yield than obtained using common fluorophores. These probes are non-photobleaching
and can be used alongside fluorophores without interference. We demonstrated
three distinct biomedical applications: (a) molecular imaging of blood
vessels, (b) tracking of nanodrug carriers in tumors, and (c) mapping
of lesions and immune cells in a multiple sclerosis mouse model. Our
strategy establishes a distinct yet complementary set of imaging probes
for understanding disease mechanisms in three dimensions