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<p>Recent advances in nanotechnology have led to the application of nanoparticles
in a wide variety of fields. In the field of nanomedicine, there is great emphasis
on combining diagnostic and therapeutic modalities into a single nanoparticle construct
(theranostics). In particular, anisotropic nanoparticles have shown great potential
for surface-enhanced Raman scattering (SERS) detection due to their unique optical
properties. Gold nanostars are a type of anisotropic nanoparticle with one of the
highest SERS enhancement factors in a non-aggregated state. By utilizing the distinct
characteristics of gold nanostars, new plasmonic materials for diagnostics, therapy,
and sensing can be synthesized. The work described herein is divided into two main
themes. The first half presents a novel, theranostic nanoplatform that can be used
for both SERS detection and photodynamic therapy (PDT). The second half involves
the rational design of silver-coated gold nanostars for increasing SERS signal intensity
and improving reproducibility and quantification in SERS measurements. </p><p>The
theranostic nanoplatforms consist of Raman-labeled gold nanostars coated with a silica
shell. Photosensitizer molecules for PDT can be loaded into the silica matrix, while
retaining the SERS signal of the gold nanostar core. SERS detection and PDT are performed
at different wavelengths, so there is no interference between the diagnostic and therapeutic
modalities. Singlet oxygen generation (a measure of PDT effectiveness) was demonstrated
from the drug-loaded nanocomposites. In vitro testing with breast cancer cells showed
that the nanoplatform could be successfully used for PDT. When further conjugating
the nanoplatform with a cell-penetrating peptide (CPP), efficacy of both SERS detection
and PDT is enhanced. </p><p>The rational design of plasmonic nanoparticles for SERS
sensing involved the synthesis of silver-coated gold nanostars. Investigation of the
silver coating process revealed that preservation of the gold nanostar tips was necessary
to achieve the increased SERS intensity. At the optimal amount of silver coating,
the SERS intensity is increased by over an order of magnitude. It was determined that
a majority of the increased SERS signal can be attributed to reducing the inner filter
effect, as the silver coating process moves the extinction of the particles far away
from the laser excitation line. To improve reproducibility and quantitative SERS detection,
an internal standard was incorporated into the particles. By embedding a small-molecule
dye between the gold and silver surfaces, SERS signal was obtained both from the internal
dye and external analyte on the particle surface. By normalizing the external analyte
signal to the internal reference signal, reproducibility and quantitative analysis
are improved in a variety of experimental conditions.</p>
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