Noble metal based plasmonic nanomaterials and their application for bio-imaging and photothermal therapy
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During the past two decades, researchers have gained more and more insight into the manipulation of nanomaterials to create useful technologies. Numerous classes of nanomaterials have been produced and studied based upon their intriguing chemical and physical properties and their potential applications in diverse fields, ranging from electronics to renewable energy and biomedicine. In this dissertation, we describe the synthesis and potential biomedical applications of several types of noble metal-based nanomaterials in which we control size, shape, and coupling to other materials to tune their localized surface plasmon resonance (LSPR) interaction with light. We demonstrate the application of these novel nanostructures as contrast agents for photoacoustic imaging and as photosensitizers for photothermal therapy. Chapter one first presents protocols for producing monodisperse spherical nanoparticles of gold and silver. The diameter of the nanospheres can be adjusted from less than 2 nm to greater than 10 nm by controlling the reaction conditions, including ligands that cap the nanosphere surfaces, reaction time, and reaction temperature. Next, we describe the synthesis of multi-branched Au nanocrystals with predominantly tripodal, tetrapodal and star-shaped morphologies. We demonstrate tuning of the LSPR energy in these materials by changing the branch length. In the third part of this chapter, we present a novel method for coupling heavily-doped p-type copper selenide (Cu 2-x Se) NPs with Au NPs by seeded nanocrystal growth to form a new type of semiconductor-metal heterogeneous nanostructure. This new class of plasmonic nanomaterials can simultaneously exhibit two types of LSPR in a single system, producing a broad optical absorbance that is nearly flat across the near infrared (NIR) spectral region (750-1150nm), along with a small shoulder at 566 nm that originates from the Au NP. We conclude this first chapter by demonstrating the use of self-doped copper sulfide (Cu 2-x S) NCs as a template for preparing gold sulfide (Au 2 S) NCs and intermediate Cu 2-x S-Au2S heterostructures by cation exchange. In chapter two, we demonstrate the use of Au-Cu 2-x Se nano-dimers for high contrast multimodal imaging in vitro and in vivo. Their broad LSPR absorbance and scattering enables both dark-field optical imaging and photoacoustic (PA) imaging with different light sources. The clinical relevance of these new PA contrast agents was demonstrated through deep tissue visualization of a sentinel lymph node (SLN) in a rat. Imaging through layers of chicken breast tissue at total imaging depths needed for human SLN imaging was achieved. Further, the kinetics of these NCs in the rat circulatory system were monitored in vivo. A widely available and relatively low cost Nd:YAG laser source(1064 nm) was used for all PA imaging experiments, which is an additional benefit for easy commercialization and clinical translation. Thus, these unique Au-Cu 2-x Se heterodimer NPs provide a promising optical contrast agent for deep tissue imaging by PAT, as well as a new material system for fundamental studies of plasmonic interactions. In chapter three, we study the potential of both Au-Cu 2-x Se NCs and multi-branched Au NCs for use in photothermal therapy (PTT). Upon illumination with a 980 nm laser beam, the Au-Cu 2-x Se nanocrystals produce significant photothermal heating, exhibiting a photothermal transduction efficiency of 32%, which is comparable to that of Au nanorods and nanoparticles (10nm). The multi-branched Au NCs exhibited a photothermal transduction efficiency of 60%, significantly higher than other materials tested in this study. In vitro photothermal heating of either Au-Cu 2-x Se nanocrystals or multi-branched Au nanocrystals in the presence of human cervical cancer cells caused effective cell ablation after 10 min laser irradiation at 1.34 W/cm 2 . Cell viability assays demonstrate that the two classes of nanocrystals are biocompatible at doses needed for photothermal therapy. Although the photothermal transduction efficiency of the multibranched Au NCs was higher than the other materials, they proved somewhat less effective for photothermal ablation of cells. We attribute this to decreased uptake of these relatively large nanostructures compared to the smaller Au-Cu 2-x Se NCs. The calibration and analysis above suggest that the Au-Cu 2-x Se NCs and the multi-branched Au NCs can serve as promising new photothermal therapy agents.