The self-assembly of colloids is an alternative to top-down processing that enables the fabrication of nanostructures. We show that self-assembled clusters of metal-dielectric spheres are the basis for nanophotonic structures. By tailoring the number and position of spheres in close-packed clusters, plasmon modes exhibiting strong magnetic and Fano-like resonances emerge. The use of identical spheres simplifies cluster assembly and facilitates the fabrication of highly symmetric structures. Dielectric spacers are used to tailor the interparticle spacing in these clusters to be approximately 2 nanometers. These types of chemically synthesized nanoparticle clusters can be generalized to other two- and three-dimensional structures and can serve as building blocks for new metamaterials.

CONSPECTUS Recent advances in theranostics have expanded our ability to design and construct multifunctional nanoparticles that will ultimately allow us to image and treat diseases in a single clinical procedure. Theranostic nanoparticles, combining targeting, therapeutic and diagnostic functions within a single nanoscale complex, have emerged as a result of this confluence of nanoscience and biomedicine. The theranostic capabilities of gold nanoshells -spherical, silica core, gold shell nanoparticles- have attracted tremendous attention over the past decade as nanoshells have emerged as a promising tool for cancer therapy and bioimaging enhancement. This account examines the design and synthesis of nanoshell-based theranostic agents, their plasmon-derived optical properties and their corresponding applications. Nanoshells illuminated with resonant light are either strong optical absorbers or scatterers, properties which give rise to their unique capabilities. In this account, we discuss the underlying physical principles contributing to the photothermal response of nanoshells. We elucidate the photophysics of nanoshell-induced fluorescence enhancement of weak near-infrared fluorophores. We then describe the application of nanoshells as a contrast agent for optical coherence tomography of breast carcinoma cells in vivo. We also examine the recent progress of nanoshells as a multimodal theranostic probe for near-infrared fluorescence and magnetic resonance imaging (MRI) combined with photothermal ablation of cancer cells. The design and preparation of nanoshell complexes is discussed, and their ability to enhance the photoluminescence of fluorophores while incorporating MR contrast is described. We show the theranostic potential of the multimodal nanoshells in vivo for imaging subcutaneous breast cancer tumors in animal models and their biodistribution in various tissues. We then discuss the potential of nanoshells as light-triggered gene therapy vectors. The plasmonic properties of nanoshells make them highly effective as light controlled delivery vectors, adding temporal control to the spatial control characteristic of nanoparticle-based gene therapy approaches. We describe the fabrication of DNA-conjugated nanoshell complexes and compare the efficiency of light-induced and thermally-induced DNA release of DNA. We examine light-triggered release of DAPI (4',6-diamidino-2-phenylindole) molecules, which bind reversibly to double-stranded DNA, to visualize intracellular light-induced release. Finally, we look at future prospects of nanoshell-based theranostics, the potential impact and near-term challenges of theranostic nanomedicine in the next decade.

Metallic nanoparticles influence the quantum yield and lifetime of adjacent fluorophores in a manner dependent on the properties of the nanostructure. Here we directly compare the fluorescence enhancement of the near-infrared fluorophore IR800 by Au nanoshells (NSs) and Au nanorods (NRs), where human serum albumin (HSA) serves as a spacer layer between the nanoparticle and the fluorophore. Our measurements reveal that the quantum yield of IR800 is enhanced from approximately 7% as an isolated fluorophore to 86% in a NSs-HSA-IR800 complex and 74% in a NRs-HSA-IR800 complex. This dramatic increase in fluorescence shows tremendous potential for contrast enhancement in fluorescence-based bioimaging.

Destruction of hypoxic regions within tumors, virtually inaccessible to cancer therapies, may well prevent malignant progression. The tumor's recruitment of monocytes into these regions may be exploited for nanoparticle-based delivery. Monocytes containing therapeutic nanoparticles could serve as "Trojan Horses" for nanoparticle transport into these tumor regions. Here we report the demonstration of several key steps toward this therapeutic strategy: phagocytosis of Au nanoshells, and photoinduced cell death of monocytes/macrophages as isolates and within tumor spheroids.