Roadmap for metal nanoparticles in radiation therapy: current status, translational challenges, and future directions.

This roadmap outlines the potential roles of metallic nanoparticles (MNPs) in the field of radiation therapy. MNPs made up of a wide range of materials (from Titanium, Z = 22, to Bismuth, Z = 83) and a similarly wide spectrum of potential clinical applications, including diagnostic, therapeutic (radiation dose enhancers, hyperthermia inducers, drug delivery vehicles, vaccine adjuvants, photosensitizers, enhancers of immunotherapy) and theranostic (combining both diagnostic and therapeutic), are being fabricated and evaluated. This roadmap covers contributions from experts in these topics summarizing their view of the current status and challenges, as well as expected advancements in technology to address these challenges.

Applications of nanoparticles in nanomedicine.

The highly tunable physical and optical properties and the ability to bind an ever expanding library of ligands have catapulted nanoparticles into nearly every discipline of scientific research. As nanoparticles inch closer to being fully deployed at the clinical level, some of the recent advances in the applications of nanoparticles in medicine are reviewed. From imaging and diagnostics to therapy and treatment, a variety of nanoparticles are presented along with their physical and optical properties to be used in a diverse array of medical applications. While other reviews are tailored to specific applications or to single nanoparticle types, this review aims to offer a more widespread view on visualization, diagnosis and treatment of disease with various types of nanoparticles.

Irradiation of gold nanoparticles by x-rays: Monte Carlo simulation of dose enhancements and the spatial properties of the secondary electrons production.

PURPOSE: The aim of this study is to understand the characteristics of secondary electrons generated from the interaction of gold nanoparticles (GNPs) with x-rays as a function of nanoparticle size and beam energy and thereby further the understanding of GNP-enhanced radiotherapy. METHODS: The effective range, deflection angle, dose deposition, energy, and interaction processes of electrons produced from the interaction of x-rays with a GNP were calculated by Monte Carlo simulations. The GEANT4 code was used to simulate and track electrons generated from a 2, 50, and 100 nm diameter GNP when it is irradiated with a 50 kVp, 250 kVp, cobalt-60, and 6 MV photon beam in water. RESULTS: When a GNP was present, depending on the beam energies used, secondary electron production was increased by 10- to 2000-fold compared to an absence of a GNP. Low-energy photon beams were much more efficient at interacting with the GNP by two to three orders of magnitude compared to MV energies and increased the deflection angle. GNPs with larger diameters also contributed more dose. The majority of the energy deposition was outside the GNP, rather than self-absorbed by the nanoparticle. The mean effective range of electron tracks for the beams tested ranged from approximately 3 microm to 1 mm. CONCLUSIONS: These simulated results yield important insights concerning the spatial distributions and elevated dose in GNP-enhanced radiotherapy. The authors conclude that the irradiation of GNP at lower photon energies will be more efficient for cell killing. This conclusion is consistent with published studies.

Intracellular uptake, transport, and processing of nanostructures in cancer cells.

Nanotechnology has been used to provide advanced biomedical research tools in diagnostic imaging and therapy, which requires targeting of nanoparticles (NPs) to individual cells and subcellular compartments. However, a complete understanding of the intracellular uptake, transport, and subcellular distribution of nanostructured materials remains limited. Hence, gold NPs were explored as a model system to study the intracellular behavior of NPs in real time. Our results show that the cellular uptake of gold NPs is dependent on their size and surface properties. The NPs were transported in vesicles of 300-500 nm diameter within the cytoplasm. The average velocity and diffusion coefficient of the vesicles containing NPs were 10.2 (+/-1.8) microm/hr and 3.33 (+/-0.52) microm 2/hr, respectively. Analysis of the time-dependent intracellular spatial distribution of the NPs demonstrated that they reside in lysosomes (final degrading organelles) within 40 minutes of incubation. These findings can be used to tailor nanoscale devices for effective cell targeting and delivery.

Elucidating the mechanism of cellular uptake and removal of protein-coated gold nanoparticles of different sizes and shapes.

We investigated the mechanism by which transferrin-coated gold nanoparticles (Au NP) of different sizes and shapes entered mammalian cells. We determined that transferrin-coated Au NP entered the cells via clathrin-mediated endocytosis pathway. The NPs exocytosed out of the cells in a linear relationship to size. This was different than the relationship between uptake and size. Furthermore, we developed a mathematical equation to predict the relationship of size versus exocytosis for different cell lines. These studies will provide guidelines for developing NPs for imaging and drug delivery applications, which will require "controlling" NP accumulation rate. These studies will also have implications in determining nanotoxicity.

Determining the size and shape dependence of gold nanoparticle uptake into mammalian cells.

We investigated the intracellular uptake of different sized and shaped colloidal gold nanoparticles. We showed that kinetics and saturation concentrations are highly dependent upon the physical dimensions of the nanoparticles (e.g., uptake half-life of 14, 50, and 74 nm nanoparticles is 2.10, 1.90, and 2.24 h, respectively). The findings from this study will have implications in the chemical design of nanostructures for biomedical applications (e.g., tuning intracellular delivery rates and amounts by nanoscale dimensions and engineering complex, multifunctional nanostructures for imaging and therapeutics).