T98G Cell Death Induced by Photothermal Treatment with Hollow Gold Nanoshell-Coupled Silica Microrods Prepared from Escherichia Coli.

As an alternative to traditional cancer treatment, photothermal therapy is a promising method with advantages such as noninvasiveness and high efficiency. Herein, we synthesized armored golden Escherichia coli (AGE) microrods as photothermal agents to evaluate the viability of cancer cell. The hollow gold nanoshell (HAuNS) was synthesized for photothermal effects under the near-infrared (NIR) region using unicellular E. coli as a framework. Coupling HAuNS onto the surface of E. coli@SiO2 enhanced temperature elevation and resulted in high conversion efficiency. The synthesized AGE microrods had excellent photothermal stability under NIR laser irradiation in the five-times recycling experiment. The temperature elevation of AGE microrod solution reached 43.7 °C, which induced hyperthermia-mediated killing of tumor cells. The results of the cytotoxicity test revealed the AGE microrod-induced T98G cell death mediated via apoptosis.

Assessment of in vivo systemic toxicity and biodistribution of iron-doped silica nanoshells.

Silica nanoparticles are an emerging class of biomaterials which may be used as diagnostic and therapeutic tools for biomedical applications. In particular, hollow silica nanoshells are attractive due to their hollow core. Approximately 70% of a 500 nm nanoshell is hollow, therefore more particles can be administered on a mg/kg basis compared to solid nanoparticles. Additionally, their nanoporous shell permits influx/efflux of gases and small molecules. Since the size, shape, and composition of a nanoparticle can dramatically alter its toxicity and biodistribution, the toxicology of these nanomaterials was assessed. A single dose toxicity study was performed in vivo to assess the toxicity of 500 nm iron-doped silica nanoshells at clinically relevant doses of 10-20 mg/kg. This study showed that only a trace amount of silica was detected in the body 10 weeks post-administration. The hematology, biochemistry and pathological results show that the nanoshells exhibit no acute or chronic toxicity in mice.

Toxicity of Graphene Shells, Graphene Oxide, and Graphene Oxide Paper Evaluated with Escherichia coli Biotests.

The plate-like graphene shells (GS) produced by an original methane pyrolysis method and their derivatives graphene oxide (GO) and graphene oxide paper (GO-P) were evaluated with luminescent Escherichia coli biotests and additional bacterial-based assays which together revealed the graphene-family nanomaterials' toxicity and bioactivity mechanisms. Bioluminescence inhibition assay, fluorescent two-component staining to evaluate cell membrane permeability, and atomic force microscopy data showed GO expressed bioactivity in aqueous suspension, whereas GS suspensions and the GO-P surface were assessed as nontoxic materials. The mechanism of toxicity of GO was shown not to be associated with oxidative stress in the targeted soxS::lux and katG::lux reporter cells; also, GO did not lead to significant mechanical disruption of treated bacteria with the release of intracellular DNA contents into the environment. The well-coordinated time- and dose-dependent surface charge neutralization and transport and energetic disorders in the Escherichia coli cells suggest direct membrane interaction, internalization, and perturbation (i.e., "membrane stress") as a clue to graphene oxide's mechanism of toxicity.

Self-assembled Monolayer Mediated Surface Environment Modification of Poly(vinylpyrrolidone)-Coated Hollow Au-Ag Nanoshells for Enhanced Loading of Hydrophobic Drug and Efficient Multimodal Therapy.

Hollow Au-Ag bimetallic nanoshell possessing hydrophobic interior space and hydrophilic exterior surface was prepared and its application as a chemo-thermo-gene therapeutic agent based on its high payload of multiple drugs having different water solubility was demonstrated. The multifunctional drug delivery system is based on the hydrophobic interior created by the self-assembled monolayer (SAM) of hexanethiol onto the inner surface of the hollow metallic nanoshells whereas the outer surface was mostly coated by hydrophilic biocompatible polymer. The nanoshells having surface environment modified by hexanethiol SAMs provided high capacity both for hydrophilic DNAzyme (Dz) to induce gene silencing and for hydrophobic SN38 (7-ethyl-10-hydroxycamptothecin), anticancer drug. The release of the loaded Dz and SN38 was independently triggered by an acidic environment and by photothermal temperature elevation upon irradiation, respectively. The chemo-thermo-gene multitherapy based on the present nanoshells having modified surface environment showed high efficacy in quantitative cell-based assays using Huh7 human liver cell containing hepatitis C viral NS3 gene replicon RNA.

Evaluation of the toxicity of intravenous delivery of auroshell particles (gold-silica nanoshells).

Gold nanoshells (155 nm in diameter with a coating of polyethylene glycol 5000) were evaluated for preclinical biocompatibility, toxicity, and biodistribution as part of a program to develop an injectable device for use in the photothermal ablation of tumors. The evaluation started with a complete good laboratory practice (GLP) compliant International Organization for Standardization (ISO)-10993 biocompatibility program, including cytotoxicity, pyrogenicity (US Pharmacopeia [USP] method in the rabbit), genotoxicity (bacterial mutagenicity, chromosomal aberration assay in Chinese hamster ovary cells, and in vivo mouse micronucleus), in vitro hemolysis, intracutaneous reactivity in the rabbit, sensitization (in the guinea pig maximization assay), and USP/ISO acute systemic toxicity in the mouse. There was no indication of toxicity in any of the studies. Subsequently, nanoshells were evaluated in vivo by intravenous (iv) infusion using a trehalose/water solution in a series of studies in mice, Sprague-Dawley rats, and Beagle dogs to assess toxicity for time durations of up to 404 days. Over the course of 14 GLP studies, the gold nanoshells were well tolerated and, when injected iv, no toxicities or bioincompatibilities were identified.

Gold nanoparticles in theranostic oncology: current state-of-the-art.

INTRODUCTION: In recent years, extensive multidisciplinary investigations have been carried out in the area of cancer nanotechnology. Gold nanoparticles (GNPs) have emerged as promising carrier for delivery of various pay-loads into their target. In view of their unique physicochemical and optical properties, GNPs have been exploited for multimodality imaging, tumor targeting, and as transporter of various therapeutics. Additionally, GNPs have been used as photothermal therapeutics against cancer. AREAS COVERED: This review will focus on recent progress in the field of gold nanomaterials in cancer therapy and diagnosis. Moreover, concern about the toxicity of gold nanomaterials is addressed. EXPERT OPINION: GNPs present versatile scaffolds for efficient delivery of cancer chemotherapeutics. Tuneable chemistry of the GNPs contributes to their ever increasing use in oncology research. The promises of a functional cancer therapy using GNPs have been extensively demonstrated, although the materials are still in their infancy stage and not surfaced to meet clinical standards.

Size dependent cellular uptake, in vivo fate and light-heat conversion efficiency of gold nanoshells on silica nanorattles.

Despite advances in photothermal therapy of gold nanoshells, reliable evaluations of their size dependence on the relative biological effects are needed. We report the size effects of PEGylated gold nanoshells on silica nanorattles (pGSNs) on their cellular uptake, in vivo fate and light-heat conversion efficiency in this study. The results indicate that smaller pGSNs have enhanced cellular uptake by the MCF-7 cells. For in vivo biodistribution study, pGSNs of different particle sizes (84-315 nm) distribute mainly in the liver and spleen in MCF-7 tumor-bearing BALB/c nude mice. Smaller pGSNs have a longer blood-circulation lifetime and higher light-heat conversion efficiency both in vitro and in vivo compared with larger ones. All three sizes of pGSNs can be excreted from the mice body at a slow rate and do not cause tissue toxicity after intravenous injection at a dosage of 20 mg kg(-1) for three times. The data support the feasibility of optimizing the therapeutic process for photothermal cell killing by plasmonic gold nanoshells.

Modeling the cellular impact of nanoshell-based biosensors using mouse alveolar macrophage cultures.

In this study, the relative toxicity of native gold-silica nanoshells (NS) has been compared to nanoshells modified with poly(ethylene glycol)-thiol (PEG-SH) and a Raman-active PEG, p-mercaptoaniline-poly(ethylene glycol) (pMA-PEG), in mouse alveolar macrophage cell cultures (RAW 264.7). The results from toxicity profiling using an MTT assay demonstrate that cell viability post-particle exposure is a function of three factors: nanoshell concentration, surface functionalization, and incubation time. By minimizing particle concentrations and incubation times, cell cultures are able to recover within 24 h of nanoshell removal, indicative of nanoshells having more of a cytostatic versus cytotoxic effect on macrophage cells. The mechanism of the cytostatic effect has been investigated by imaging the presence of reactive oxygen species (ROS) using a fluorescence assay kit (Image-iT™ LIVE) after the introduction of NS to the cell cultures. Elevated ROS signals are seen in the cells containing higher concentration of NS, and indicate that the major reason of toxicity may due to the oxidative stress caused by excess NS particles. Raman imaging experiments with pMA-PEG coated nanoshells showed that cells exposed for even short exposure times (∼2 h) retained those particles up to 24 h after exposure, while migration experiments suggest that surviving cells retain their nanoshells and may reallocate them to progeny cells upon cell division.

Synthesis and cytotoxicity assessment of superparamagnetic iron-gold core-shell nanoparticles coated with polyglycerol.

Core-shell iron-gold (Fe@Au) nanoparticles were synthesized by a facile reverse micelle procedure and the effect of water to surfactant molar ratio (w) on the size, size distribution and magnetic properties of the nanoparticles was studied. MTT assay was utilized to evaluate the cell toxicity of the nanoparticles. To functionalize the particles for MRI imaging and targeted drug delivery, the particles were coated by polyglycerol through capping with thiol followed by polymerization of glycidol. The characteristics of the particles were examined by X-ray diffraction (XRD), transmission electron microscopy (TEM), vibrating sample magnetometer (VSM), UV-visible spectroscopy, and Fourier transform infrared spectroscopy (FT-IR). It was found that the size and size distribution of the nanoparticles increase by increasing the water to surfactant molar ratio (w). The particles were spherical in shape with a thin layer of gold. Complementary growth of the gold shell on the iron core was noticed. Meanwhile, two types of agglomeration including magnetic beads and magnetic colloidal nanocrystals clusters were observed dependent on the w-value. The magnetic measurement studies revealed the superparamagnetic behavior of the nanoparticles. MTT assay result indicated the synthesized nanoparticles are nontoxic that will be useful for biomedical applications.