ABSTRACT
The increasing exploration of metallic nanoparticles for use as cancer therapeutic agents necessitates a sensitive technique to track the clearance and distribution of the material once introduced into a living system. Inductively coupled plasma mass spectrometry (ICP-MS) provides a sensitive and selective tool for tracking the distribution of metal components from these nanotherapeutics. This chapter presents a standardized method for processing biological matrices, ensuring complete homogenization of tissues, and outlines the preparation of appropriate standards and controls. The method described herein utilized gold nanoparticle-treated samples; however, the method can easily be applied to the analysis of other metals.
Subject(s)
Gold/analysis , Gold/pharmacokinetics , Mass Spectrometry/methods , Metal Nanoparticles/analysis , Animals , Humans , Tissue DistributionABSTRACT
Plasmon-resonant gold nanorods (GNRs) can serve as imaging agents for spectroscopic optical coherence tomography (SOCT). The aspect ratio of the GNRs are adjusted for maximum absorption in the far red to create a partial spectral overlap with the low-wavelength edge of the near-infrared SOCT imaging band. The spectroscopic absorption profile of the GNRs is incorporated into a depth-resolved algorithm for mapping the relative GNR density within OCT images. This technique enables us to image GNR distributions in excised human breast carcinomas, demonstrating their potential as OCT contrast agents in heteregeneous, highly scattering tissues.
ABSTRACT
Gold nanorods (GNRs) were encapsulated and dispersed into organic solvents by tetrabenzylthiol resorcinarene (TBTR) and by a poly(dithiocarbamate) derived from tetra- N-methyl(aminomethyl)resorcinarene (TMAR-DTC), formed by the in situ condensation of TMAR with carbon disulfide. The latter proved to be highly effective at enabling the redispersion of GNRs in various organic solvents. GNRs encapsulated in TMAR-DTC exhibited a strong solvatochromic response, with a refractive index sensitivity of over 300 nm/RIU. The resorcinarene-encapsulated GNRs could withstand high temperatures for a short period of time, and could be used to nucleate the growth of magnetic nanoshells.
ABSTRACT
Plasmon-resonant gold nanorods, which have large absorption cross sections at near-infrared frequencies, are excellent candidates as multifunctional agents for image-guided therapies based on localized hyperthermia. The controlled modification of the surface chemistry of the nanorods is of critical importance, as issues of cell-specific targeting and nonspecific uptake must be addressed prior to clinical evaluation. Nanorods coated with cetyltrimethylammonium bromide (a cationic surfactant used in nanorod synthesis) are internalized within hours into KB cells by a nonspecific uptake pathway, whereas the careful removal of cetyltrimethylammonium bromide from nanorods functionalized with folate results in their accumulation on the cell surface over the same time interval. In either case, the nanorods render the tumor cells highly susceptible to photothermal damage when irradiated at the nanorods' longitudinal plasmon resonance, generating extensive blebbing of the cell membrane at laser fluences as low as 30 J/cm2.
Subject(s)
Cell Survival/radiation effects , Gold/chemistry , Hyperthermia, Induced/methods , Mouth Neoplasms/pathology , Mouth Neoplasms/therapy , Nanomedicine/methods , Nanotubes/chemistry , Cell Line, Tumor , Dose-Response Relationship, Radiation , Humans , Materials Testing , Nanotubes/radiation effectsABSTRACT
Gold nanorods coated with cetyltrimethylammonium bromide (CTAB), a cationic micellar surfactant used in nanorod synthesis, were rapidly and irreversibly internalized by KB cells via a nonspecific uptake mechanism. Internalized nanorods near the cell surface were monitored by two-photon luminescence (TPL) microscopy and observed to migrate toward the nucleus with a quadratic rate of diffusion. The internalized nanorods were not excreted but formed permanent aggregates within the cells, which remained healthy and grew to confluence over a 5-day period. Nonspecific nanorod uptake could be greatly reduced by displacing the CTAB surfactant layer with chemisorptive surfactants, particularly by the conjugation of poly(ethylene glycol) chains onto nanorods using in situ dithiocarbamate formation.
Subject(s)
Gold/metabolism , Nanotubes , Biological Transport/drug effects , Cell Line, Tumor , Cell Membrane/drug effects , Cell Membrane/metabolism , Humans , Methylation , Microscopy, Electron, Transmission , Molecular Structure , Nanotubes/ultrastructure , Polyethylene Glycols/chemistryABSTRACT
Plasmon-resonant gold nanorods are demonstrated as low backscattering albedo contrast agents for optical coherence tomography (OCT). We define the backscattering albedo, a', as the ratio of the backscattering to extinction coefficient. Contrast agents which modify a' within the host tissue phantoms are detected with greater sensitivity by the differential OCT measurement of both a' and extinction. Optimum sensitivity is achieved by maximizing the difference between contrast agents and tissue, |a'(ca) - a'(tiss)|. Low backscattering albedo gold nanorods (14x 44 nm; lambda(max) = 780 nm) within a high backscattering albedo tissue phantom with an uncertainty in concentration of 20% (randomized 2+/-0.4% intralipid) were readily detected at 82 ppm (by weight) in a regime where extinction alone could not discriminate nanorods. The estimated threshold of detection was 30 ppm.
