This work demonstrated that ultrasmall gold nanoparticles (AuNPs) smaller than 10 nm display unique advantages over nanoparticles larger than 10 nm in terms of localization to, and penetration of, breast cancer cells, multicellular tumor spheroids, and tumors in mice. Au@tiopronin nanoparticles that have tunable sizes from 2 to 15 nm with identical surface coatings of tiopronin and charge were successfully prepared. For monolayer cells, the smaller the Au@tiopronin NPs, the more AuNPs found in each cell. In addition, the accumulation of Au NPs in the ex vivo tumor model was size-dependent: smaller AuNPs were able to penetrate deeply into tumor spheroids, whereas 15 nm nanoparticles were not. Owing to their ultrasmall nanostructure, 2 and 6 nm nanoparticles showed high levels of accumulation in tumor tissue in mice after a single intravenous injection. Surprisingly, both 2 and 6 nm Au@tiopronin nanoparticles were distributed throughout the cytoplasm and nucleus of cancer cells in vitro and in vivo, whereas 15 nm Au@tiopronin nanoparticles were found only in the cytoplasm, where they formed aggregates. The ex vivo multicellular spheroid proved to be a good model to simulate in vivo tumor tissue and evaluate nanoparticle penetration behavior. This work gives important insights into the design and functionalization of nanoparticles to achieve high levels of accumulation in tumors.
Nanoparticles offer potential as drug delivery systems for chemotherapeutics based on certain advantages of molecular drugs. In this study, we report that particle size exerts great influence on the penetration and retention behavior of nanoparticles entering tumors. On comparing gold-coated Au@tiopronin nanoparticles that were prepared with identical coating and surface properties, we found that 50 nanoparticles were more effective in all in vitro, ex vivo, and in vivo assays conducted using MCF-7 breast cells as a model system. Beyond superior penetration in cultured cell monolayers, 50 nm Au@tiopronin nanoparticles also penetrated more deeply into tumor spheroids ex vivo and accumulated more effectively in tumor xenografts in vivo after a single intravenous dose. In contrast, larger gold-coated nanoparticles were primarily localized in the periphery of the tumor spheroid and around blood vessels, hindering deep penetration into tumors. We found multicellular spheroids to offer a simple ex vivo tumor model to simulate tumor tissue for screening the nanoparticle penetration behavior. Taken together, our findings define an optimal smaller size for nanoparticles that maximizes their effective accumulation in tumor tissue. Cancer Res; 73(1); 319-30. Ó2012 AACR.
1-Nonanethiol-capped silver nanoparticles of about 4.18 nm in diameter were prepared using a liquid−liquid two-phase method. Two-dimensional ordered superlattices of the nanoparticles were formed on
carbon films coated on transmission electron microscopy (TEM) copper grids by evaporating a drop of the
dispersion in chloroform. The formation process of the silver nanoparticles was investigated by UV−visible
absorption spectroscopy and TEM. A blue shift of the maximum absorption peak position of the UV−vis
spectra occurred at the beginning of the reaction, followed by a red shift. This result indicated that large
thiol-capped silver nanoparticles were formed at the beginning, then the large particles were decomposed
into small particles, and in the final stage the small particles enlarged slightly again. The TEM images
show directly the same process with the results from the UV−vis spectra. In addition, the UV−visible
spectra of the silver nanoparticle colloidal phase obtained finally show that the system is monodisperse
and can remain stable for several weeks.
Diffusion of target molecules incorporated in the self-spreading lipid bilayer was controlled by the introduction of periodic array of metallic architecture on solid surface. Retardation of the progress of target molecules became significant when the size of gap between small metal architectures was less than a few hundred nanometers. The self-spreading dynamics of the lipid bilayer depending on the size of the small gap were analyzed semiquantitatively. Estimated change in the driving force of the spreading layer suggests that highly localized compression of the spreading layer causes selective segregation of molecules.
Au–ZnO matchstick-shaped nanorods with a good epitaxial interface have shown a strong SERS effect, which is attributed to the plasmon-induced hot-electron transfer from Au tips to ZnO nanorods.
Two- and three-dimensional superlattices of passivated silver nanoparticles
were formed on amorphous carbon films by the self-assembly technique. The x-ray
diffraction (XRD) and x-ray photoelectron spectroscopy results
demonstrated that the colloid system was composed of silver nanoparticles
and, on the surface of the silver nanoparticles, the chemical bond was formed
between the S of the 1-nonanethiol and the Ag of the particle. XRD and
transmission electron microscopy also showed that the instability of
the silver nanoparticles mainly resulted from the growth of
the nanoparticles. Due to the relatively close-packed thiol layer on the
surface of the nanoparticle, in the infrared spectra of the silver nanoparticles,
absorption peaks of the terminal methyl group and methylene stretching modes
were red shifted; meanwhile the transverse modes of the binding absorption
disappeared.
After investigating the effects of the interior wall of the micro-capillary tube on the size distribution of silver nanoparticles, the well dispersed silver nanoparticles were fabricated continuously in a selected PTFE micro-capillary reactor with a one-step process.
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