Much of the current excitement surrounding nanoscience is directly connected to the promise of new nanoscale applications in cancer diagnostics and therapy. Because of their strongly resonant light-absorbing and light-scattering properties that depend on shape, noble metal nanoparticles provide a new and powerful tool for innovative light-based approaches. Nanoshellsspherical, dielectric core, gold shell nanoparticleshave been central to the development of photothermal cancer therapy and diagnostics for the past several years. By manipulating nanoparticle shape, researchers can tune the optical resonance of nanoshells to any wavelength of interest. At wavelengths just beyond the visible spectrum in the near-infrared, blood and tissue are maximally transmissive. When nanoshell resonances are tuned to this region of the spectrum, they become useful contrast agents in the diagnostic imaging of tumors. When illuminated, they can serve as nanoscale heat sources, photothermally inducing cell death and tumor remission. As nanoshell-based diagnostics and therapeutics move from laboratory studies to clinical trials, this Account examines the highly promising achievements of this approach in the context of the challenges of this complex disease. More broadly, these materials present a concrete example of a highly promising application of nanochemistry to a biomedical problem. We describe the properties of nanoshells that are relevant to their preparation and use in cancer diagnostics and therapy. Specific surface chemistries are necessary for passive uptake of nanoshells into tumors and for targeting specific cell types by bioconjugate strategies. We also describe the photothermal temperature increases that can be achieved in surrogate structures known as tissue phantoms and the accuracy of models of this effect using heat transport analysis. Nanoshell-based photothermal therapy in several animal models of human tumors have produced highly promising results, and we include nanoparticle dosage information, thermal response, and tumor outcomes for these experiments. Using immunonanoshells, infrared diagnostic imaging contrast enhancement and photothermal therapy have been integrated into a single procedure. Finally, we examine a novel "Trojan horse" strategy for nanoparticle delivery that overcomes the challenge of accessing and treating the hypoxic regions of tumors, where blood flow is minimal or nonexistent. The ability to survive hypoxia selects aggressive cells which are likely to be the source of recurrence and metastasis. Treatment of these regions has been incredibly difficult. Ultimately, we look beyond the current research and assess the next challenges as nanoshell-based photothermal cancer therapy is implemented in clinical practice.
Solar illumination of broadly absorbing metal or carbon nanoparticles dispersed in a liquid produces vapor without the requirement of heating the fluid volume. When particles are dispersed in water at ambient temperature, energy is directed primarily to vaporization of water into steam, with a much smaller fraction resulting in heating of the fluid. Sunlight-illuminated particles can also drive H(2)O-ethanol distillation, yielding fractions significantly richer in ethanol content than simple thermal distillation. These phenomena can also enable important compact solar applications such as sterilization of waste and surgical instruments in resource-poor locations.
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.
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