Highly stable PEGylated gold nanoparticles in water: applications in biology and catalysis

Gold nanoparticles (Au NPs) with diameters ranging between 5-60 nm have been synthesised in water, and further stabilized with polyethylene glycol-based thiol polymers (mPEG-SH). Successful PEGylation of the Au NPs was confirmed by Dynamic Light scattering (DLS) and Zeta potential measurements. PEG coating of the Au NPs is the key of their colloidal stabilty, and its successful applications. Catalytic efficiency testing of the PEG-AuNPs were carried out on homocoupling of boronic acid. PEG-Au NPs with AuNps diameter < 30 nm were useful as catalyst in water. Finally, the PEG-Au NPs were also shown to be stable in biological fluid and not cytotoxic on B16.F10 cell line, making them attractive for further studies.

A Comparative Review of Computational Methods as Applied to Gold(I) Complexes and Mechanisms

In the last two decades, the field of homogeneous gold catalysis has been

extremely active, growing at a rapid pace. Another rapidly-growing field—that of

computational chemistry—has often been applied to the investigation of various gold-

catalyzed reaction mechanisms. Unfortunately, a number of recent mechanistic studies

have utilized computational methods that have been shown to be inappropriate and

inaccurate in their description of gold chemistry. This work presents an overview of

available computational methods with a focus on the approximations and limitations

inherent in each, and offers a review of experimentally-characterized gold(I) complexes

and proposed mechanisms as compared with their computationally-modeled

counterparts. No aim is made to identify a “recommended” computational method for

investigations of gold catalysis; rather, discrepancies between experimentally and

computationally obtained values are highlighted, and the systematic errors between

different computational methods are discussed.

Hydroxylamine-O-sulfonic acid as a new reducing agent for the formation of nearly monodisperse gold nanoparticles in water: synthesis, characterisation and bioconjugation

Gold nanoparticles (Au NPs) with diameters ranging between 15 and 150 nm have been synthesised in water. 15 and 30 nm Au NPs were obtained by the Turkevich and Frens method using sodium citrate as both a reducing and stabilising agent at high temperature (Au NPs-citrate), while 60, 90 and 150 nm Au NPs were formed using hydroxylamine-o-sulfonic acid (HOS) as a reducing agent for HAuCl4 at room temperature. This new method using HOS is an extension of the approaches previously reported for producing Au NPs with mean diameters above 40 nm by direct reduction. Functionalised polyethylene glycol-based thiol polymers were used to stabilise the pre-synthesised Au NPs. The nanoparticles obtained were characterised using uv-visible spectroscopy, dynamic light scattering (DLS) and transmission electron microscopy (TEM). Further bioconjugation on 15, 30 and 90 nm PEGylated Au NPs were performed by grafting Bovine Serum Albumin, Transferrin and Apolipoprotein E (ApoE).

Again on the enforceable chart of don Francisco Pizarro: the arrival of American gold stocks to Spain (1536-1553)

Besides researching the last goal of the execution of a trial between Francisco Pizarro, governor of Peru, and his mandatory, Pedro de Barrantes on behalf of the gold sent to Spain, the present work reviews all the data found in the Archives of the Grenade Chancellery on the arrival of gold to Spain. Also, a curious trial on a subject of Preste Juan is included.

Heat Dissipation of Hybrid Iron Oxide-Gold Nanoparticles in an Agar Phantom

Hybrid iron oxide-gold nanoparticles (HNPs) have shown potential in cancer therapy as agents for tumour ablation
and thermal switches for targeted drug release. Heat generation occurs by exploitation of the surface plasmon
resonance of the gold coating, which usually occurs at the maximum UV absorption wavelength. However, lasers
at such wavelength are often expensive and highly specialised. Here, we report the heating and monitoring of heat
dissipation of HNPs suspended in agar phantoms using a relatively inexpensive Ng: YAG pulsed 1064 nm laser source.
The particles experience heating of up to 40°C with a total area of heat dissipation up to 132.73 mm2 from the 1 mm
diameter irradiation point after 60 seconds. This work reports the potential and possible drawbacks of these particles
for translation into cancer therapy based on our findings.

Gold nanoparticle induced vasculature damage in radiotherapy: Comparing protons, megavoltage photons, and kilovoltage photons

Purpose: The purpose of this work is to investigate the radiosensitizing effect of gold nanoparticle (GNP) induced vasculature damage for proton, megavoltage (MV) photon, and kilovoltage (kV) photon irradiation. Methods: Monte Carlo simulations were carried out using tool for particle simulation (TOPAS) to obtain the spatial dose distribution in close proximity up to 20 µm from the GNPs. The spatial dose distribution from GNPs was used as an input to calculate the dose deposited to the blood vessels. GNP induced vasculature damage was evaluated for three particle sources (a clinical spread out Bragg peak proton beam, a 6 MV photon beam, and two kV photon beams). For each particle source, various depths in tissue, GNP sizes (2, 10, and 20 nm diameter), and vessel diameters (8, 14, and 20 µm) were investigated. Two GNP distributions in lumen were considered, either homogeneously distributed in the vessel or attached to the inner wall of the vessel. Doses of 30 Gy and 2 Gy were considered, representing typical in vivo enhancement studies and conventional clinical fractionation, respectively. Results: These simulations showed that for 20 Au-mg/g GNP blood concentration homogeneously distributed in the vessel, the additional dose at the inner vascular wall encircling the lumen was 43% of the prescribed dose at the depth of treatment for the 250 kVp photon source, 1% for the 6 MV photon source, and 0.1% for the proton beam. For kV photons, GNPs caused 15% more dose in the vascular wall for 150 kVp source than for 250 kVp. For 6 MV photons, GNPs caused 0.2% more dose in the vascular wall at 20 cm depth in water as compared to at depth of maximum dose (Dmax). For proton therapy, GNPs caused the same dose in the vascular wall for all depths across the spread out Bragg peak with 12.7 cm range and 7 cm modulation. For the same weight of GNPs in the vessel, 2 nm diameter GNPs caused three times more damage to the vessel than 20 nm diameter GNPs. When the GNPs were attached to the inner vascular wall, the damage to the inner vascular wall can be up to 207% of the prescribed dose for the 250 kVp photon source, 4% for the 6 MV photon source, and 2% for the proton beam. Even though the average dose increase from the proton beam and MV photon beam was not large, there were high dose spikes that elevate the local dose of the parts of the blood vessel to be higher than 15 Gy even for 2 Gy prescribed dose, especially when the GNPs can be actively targeted to the endothelial cells. Conclusions: GNPs can potentially be used to enhance radiation therapy by causing vasculature damage through high dose spikes caused by the addition of GNPs especially for hypofractionated treatment. If GNPs are designed to actively accumulate at the tumor vasculature walls, vasculature damage can be increased significantly. The largest enhancement is seen using kilovoltage photons due to the photoelectric effect. Although no significant average dose enhancement was observed for the whole vasculature structure for both MV photons and protons, they can cause high local dose escalation (>15 Gy) to areas of the blood vessel that can potentially contribute to the disruption of the functionality of the blood vessels in the tumor.

Comparing gold nano-particle enhanced radiotherapy with protons, megavoltage photons and kilovoltage photons: a Monte Carlo simulation

Gold nanoparticles (GNPs) have shown potential to be used as a radiosensitizer for radiation therapy. Despite extensive research activity to study GNP radiosensitization using photon beams, only a few studies have been carried out using proton beams. In this work Monte Carlo simulations were used to assess the dose enhancement of GNPs for proton therapy. The enhancement effect was compared between a clinical proton spectrum, a clinical 6 MV photon spectrum, and a kilovoltage photon source similar to those used in many radiobiology lab settings. We showed that the mechanism by which GNPs can lead to dose enhancements in radiation therapy differs when comparing photon and proton radiation. The GNP dose enhancement using protons can be up to 14 and is independent of proton energy, while the dose enhancement is highly dependent on the photon energy used. For the same amount of energy absorbed in the GNP, interactions with protons, kVp photons and MV photons produce similar doses within several nanometers of the GNP surface, and differences are below 15% for the first 10 nm. However, secondary electrons produced by kilovoltage photons have the longest range in water as compared to protons and MV photons, e.g. they cause a dose enhancement 20 times higher than the one caused by protons 10 μm away from the GNP surface. We conclude that GNPs have the potential to enhance radiation therapy depending on the type of radiation source. Proton therapy can be enhanced significantly only if the GNPs are in close proximity to the biological target.

Roadmap to clinical use of gold nanoparticles for radiation sensitization

The past decade has seen a dramatic increase in interest in the use of gold nanoparticles (GNPs) as radiation sensitizers for radiation therapy. This interest was initially driven by their strong absorption of ionizing radiation and the resulting ability to increase dose deposited within target volumes even at relatively low concentrations. These early observations are supported by extensive experimental validation, showing GNPs' efficacy at sensitizing tumors in both in vitro and in vivo systems to a range of types of ionizing radiation, including kilovoltage and megavoltage X rays as well as charged particles. Despite this experimental validation, there has been limited translation of GNP-mediated radiation sensitization to a clinical setting. One of the key challenges in this area is the wide range of experimental systems that have been investigated, spanning a range of particle sizes, shapes, and preparations. As a result, mechanisms of uptake and radiation sensitization have remained difficult to clearly identify. This has proven a significant impediment to the identification of optimal GNP formulations which strike a balance among their radiation sensitizing properties, their specificity to the tumors, their biocompatibility, and their imageability in vivo. This white paper reviews the current state of knowledge in each of the areas concerning the use of GNPs as radiosensitizers, and outlines the steps which will be required to advance GNP-enhanced radiation therapy from their current pre-clinical setting to clinical trials and eventual routine usage.

Preclincial evaluation of Gold-DTDTPA Nanoparticles As Theranostic Agents In Prostate Cancer Radiotherapy

AIM: Gold nanoparticles have attracted significant interest in cancer diagnosis and treatment. Herein, we evaluated the theranostic potential of dithiolated diethylenetriamine pentaacetic acid (DTDTPA) conjugated AuNPs (Au@DTDTPA) for CT-contrast enhancement and radiosensitization in prostate cancer.

MATERIALS & METHODS: In vitro assays determined Au@DTDTPA uptake, cytotoxicity, radiosensitizing potential and DNA damage profiles. Human PC3 xenograft tumor models were used to determine CT enhancement and radiation modulating effects in vivo.

RESULTS: Cells exposed to nanoparticles and radiation observed significant additional reduction in survival compared with radiation only. Au@DTDTPA produced a CT enhancement of 10% and a significant extension in tumor growth delay from 16.9 days to 38.3 compared with radiation only.

CONCLUSION: This study demonstrates the potential of Au@DTDTPA to enhance CT-image contrast and simultaneously increases the radiosensitivity of prostate tumors.