Metallic nanoparticles have been widely used in a variety of imaging and therapeutic applications due to their unique
optical properties in the visible and near-infrared (NIR) regions - for example, various plasmonic nanoparticles are used
for molecular photoacoustic imaging and photothermal therapy. However, there are concerns that these agents may not
be safe under physiological conditions, because these nanoparticles are not biodegradable, could accumulate and,
therefore, could be toxic long-term. We investigate the feasibility of using biodegradable gold nanoclusters as a contrast
agent for highly sensitive photoacoustic imaging. The size of these biodegradable nanoclusters, consisting of sub-5 nm
primary gold particles and a biodegradable polymer binder, is less than 100 nm. Due to plasmon coupling, these
nanoclusters are characterized by a broad extinction spectrum that extends to the near infrared (NIR) spectral range.
Photoacoustic imaging of tissue models containing inclusions with different concentrations of nanoparticles was
performed using a tunable pulsed laser system. The results indicate that the biodegradable nanoclusters, comprised of
small gold nanoparticles, can be used as contrast agents in photoacoustic imaging.
Nanoparticles such as gold and silver with plasmonic resonances in the near-infrared (NIR) optical region,
where soft tissue is the most transparent, are of great interest in biomedical applications. A major roadblock
in translation of inorganic nanoparticles to clinical practice for systemic targeting of disease is their nonbiodegradable
nature. In addition, gold nanoparticles that absorb in the NIR are typically greater than 50 nm,
which is above the threshold size of 5.5 nm required for effective excretion from the body. Here we describe
a new class of biodegradable gold nanoparticles with plasmon resonances in the NIR region. The synthesis is
based on controlled assembly of very small (less than 5 nm) primary gold particles into nanoclusters with
sub-100 nm overall diameter and an intense NIR absorbance. The assembly is mediated by biodegradable
polymers, polyethylene glycol (PEG) and polylactic acid (PLA) copolymer, and small capping ligands on the
constituent nanoparticles. Nanoclusters deaggregate into sub-5nm primary gold particles upon biodegradation
of the polymer binder in live cells over one week, as shown by dark-field reflectance and hyperspectral
imaging.
Nanoparticles such as gold and silver with plasmonic resonances in the near-infrared (NIR) optical region,
where soft tissue is the most transparent, are of great interest in biomedical applications. A major roadblock
in translation of inorganic nanoparticles to clinical practice for systemic targeting of disease is their nonbiodegradable
nature. In addition, gold nanoparticles that absorb in the NIR are typically greater than 50 nm,
which is above the threshold size of 5.5 nm required for effective excretion from the body. Here we describe
a new class of biodegradable gold nanoparticles with plasmon resonances in the NIR region. The synthesis is
based on controlled assembly of very small (less than 5 nm) primary gold particles into nanoclusters with
sub-100 nm overall diameter and an intense NIR absorbance. The assembly is mediated by biodegradable
polymers, polyethylene glycol (PEG) and polylactic acid (PLA) copolymer, and small capping ligands on the
constituent nanoparticles. Nanoclusters deaggregate into sub-5nm primary gold particles upon biodegradation
of the polymer binder in live cells over one week, as shown by dark-field reflectance and hyperspectral
imaging.
The clinical applicability of antibodies and plasmonic nanosensors as topically applied, molecule-specific optical diagnostic agents for noninvasive early detection of cancer and precancer is severely limited by our inability to efficiently deliver macromolecules and nanoparticles through mucosal tissues. We have developed an imidazole-functionalized conjugate of the polysaccharide chitosan (chitosan-IAA) to enhance topical delivery of contrast agents, ranging from small molecules and antibodies to gold nanoparticles up to 44 nm in average diameter. Contrast agent uptake and localization in freshly resected mucosal tissues was monitored using confocal microscopy. Chitosan-IAA was found to reversibly enhance mucosal permeability in a rapid, reproducible manner, facilitating transepithelial delivery of optical contrast agents. Permeation enhancement occurred through an active process, resulting in the delivery of contrast agents via a paracellular or a combined paracellular/transcellular route depending on size. Coadministration of epidermal growth factor receptor-targeted antibodies with chitosan-IAA facilitated specific labeling and discrimination between paired normal and malignant human oral biopsies. Together, these data suggest that chitosan-IAA is a promising topical permeation enhancer for mucosal delivery of optical contrast agents.
A spectropolarimeter utilizing an Oriel MIR8000 Fourier Transform Spectrometer in the MWIR is demonstrated. The
use of the channeled spectral technique, originally developed by K. Oka, is created with the use of two AR coated
Yttrium Vanadate (YVO4) crystal retarders with a 2:1 thickness ratio. A basic mathematical model for the system is
presented, showing that the Stokes parameters are directly present in the interferogram. Theoretical results are then
compared with real data from the system, an improved model is provided to simulate the effects of absorption within the
crystal, and error between reconstructions with phase-corrected and raw interferograms is analyzed.
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