<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> / Dissertation

<p>The advancement in nanotechnology creates a new perspective on future medicine. With more and more understanding on controlling the functional behavior of the nanoplatform, scientists nowadays are aiming to improve the health care system by offering personalized medicine through nanotechnology. Lots of emphasis have been placed on a promising field called theranostics, which integrate imaging and therapeutic functions into one, that not only offers monitoring and imaging of the biological process, but also provides diagnosis and drug delivery simultaneously. Plasmonic gold nanostars, because of its anisotropic geometry and unique plasmonic property, have become one of the most anticipated nanoplatform in the field of nanotheranostics, aiming to achieve superior plasmonic properties for biomedical applications. The work herein will provide an introduction to the related field on plasmonics, nanobiophotonics and nanotheranostics. A facile plasmon-tunable surfactant-free nanostars synthesis method is described followed by an extensive characterization both computationally and experimentally. Its superior plasmon behavior on two-photon photoluminescence imaging and surface-enhanced Raman scattering detection are demonstrated both in cells and in animals. Therapeutic function assessment is carried out both as drug carriers (photodynamic therapy) and as endogenous stimulus responsive agents (photothermal therapy). Finally, the nanostars' cellular uptake mechanism is investigated based on nanostars' endogenous contrast; an enhanced photothermal therapy is achieved using an ultralow irradiance that has ever published. With nanostars being a novel and powerful theranostic agent, the potentials implication lies in the study of their pharmacokinetics, targeted delivery, diagnostic imaging, and toxicity.</p> / Dissertation