Theranostic Nanoshells: From Probe Design to Imaging and Treatment of Cancer

Abstract

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.

Monitoring Aptamer–Protein Interactions Using Tunable Resistive Pulse Sensing

“…Synthesis and fabrication methods for nanoparticles in solution have evolved to the extent that particle size, shape, and composition can be easily modified. Technology platforms have also become more robust and reproducible to the extent that assays based upon nanomaterials offer significant advantages over conventional diagnostic systems with regard to assay sensitivity, selectivity, and practicality [6][7][8][9][10][11][12][13] . Following the advancement of material synthesis, a range of new characterisation technologies capable of monitoring and measuring the size, surface chemistry, shape, optical, magnetic and even electrochemical properties have emerged [14][15][16][17][18][19][20] .…”

Plasmas meet plasmonics

“…Moving clockwise from the top left hand corner, these include: a (proposed) plasmon cloaking device [174,175], single-molecule SERS sensing platforms that rely on plasmonic hot spots [169], theranostics [170], surface plasmon lasers or 'spasers' [173,176,177], LSPR biosensors using simple LEDs [172], nextgeneration photovoltaic cells [87] and plasmon rulers [171]. This is of course a non-exhaustive list that is meant to just give an idea of how many fields plasmonics is involved in.…”

“…Biomedicine and the convergence of plasmonics and plasmas: an example of a biomedical application (excluding sensors) which involves plasmons is photothermal therapy [170,[203][204][205] (see Fig. 5c).…”

Laser und andere Lichtquellen in der Medizintechnik

“…so scheint das ende der PdT noch lange nicht erreicht: Bei der Photothermalen Therapie (PTT) kombiniert man in künstlich hergestellten nanopartikeln therapeutische und diagnostische ansätze (Theranostik): einerseits reichern sich diese Partikel spezifisch in bestimmten Tumorgeweben an und können dort durch z. B. Fluoreszenz nachgewiesen werden, andererseits können sie lichtgesteuert therapeutisch zytotoxische Wirkung erzielen [7]. auch im Bereich Telemedizin und assisted Living kann man sich einsatzmöglichkeiten vorstellen.…”