Cancer-selective, single agent chemoradiosensitising gold nanoparticles

Two nanometre gold nanoparticles (AuNPs), bearing sugar moieties and/or thiol-polyethylene glycol-amine (PEG-amine), were synthesised and evaluated for their in vitro toxicity and ability to radiosensitise cells with 220 kV and 6 MV X-rays, using four cell lines representing normal and cancerous skin and breast tissues. Acute 3 h exposure of cells to AuNPs, bearing PEG-amine only or a 50:50 ratio of alpha-galactose derivative and PEG-amine resulted in selective uptake and toxicity towards cancer cells at unprecedentedly low nanomolar concentrations. Chemotoxicity was prevented by co-administration of N-acetyl cysteine antioxidant, or partially prevented by the caspase inhibitor Z-VAD-FMK. In addition to their intrinsic cancer-selective chemotoxicity, these AuNPs acted as radiosensitisers in combination with 220 kV or 6 MV X-rays. The ability of AuNPs bearing simple ligands to act as cancer-selective chemoradiosensitisers at low concentrations is a novel discovery that holds great promise in developing low-cost cancer nanotherapeutics

Correlation of biocapping agents with cytotoxic effects of silver nanoparticles on human tumor cells

10.1039/C3RA41346BRSC Advances314329-1433

Genotoxicity of metal oxide nanomaterials: review of recent data and discussion of possible mechanisms

Nanotechnology has rapidly entered into human society, revolutionized many areas, including technology, medicine and cosmetics. This progress is due to the many valuable and unique properties that nanomaterials possess. In turn, these properties might become an issue of concern when considering potentially uncontrolled release to the environment. The rapid development of new nanomaterials thus raises questions about their impact on the environment and human health. This review focuses on the potential of nanomaterials to cause genotoxicity and summarizes recent genotoxicity studies on metal oxide/silica nanomaterials. Though the number of genotoxicity studies on metal oxide/silica nanomaterials is still limited, this endpoint has recently received more attention for nanomaterials, and the number of related publications has increased. An analysis of these peer reviewed publications over nearly two decades shows that the test most employed to evaluate the genotoxicity of these nanomaterials is the comet assay, followed by micronucleus, Ames and chromosome aberration tests. Based on the data studied, we concluded that in the majority of the publications analysed in this review, the metal oxide (or silica) nanoparticles of the same core chemical composition did not show different genotoxicity study calls (i.e. positive or negative) in the same test, although some results are inconsistent and need to be confirmed by additional experiments. Where the results are conflicting, it may be due to the following reasons: (1) variation in size of the nanoparticles; (2) variations in size distribution; (3) various purities of nanomaterials; (4) variation in surface areas for nanomaterials with the same average size; (5) differences in coatings; (6) differences in crystal structures of the same types of nanomaterials; (7) differences in size of aggregates in solution/media; (8) differences in assays; (9) different concentrations of nanomaterials in assay tests. Indeed, due to the observed inconsistencies in the recent literature and the lack of adherence to appropriate, standardized test methods, reliable genotoxicity assessment of nanomaterials is still challenging

Gold nanoparticles with tailored monolayers for delivery applications

Gold nanoparticles (AuNPs) hold a great promise for biomedical applications. The inert inorganic core provides a scaffold to hold organic ligands and their payloads, while the diversity of monolayers provide a means to tailor AuNP surface properties for particular purposes. Based on our synthethic approach to ligand fabrication, our group has been able to control the chemical properties of AuNPs at the nanoscale level. These properties have made AuNPs an excellent scaffold for delivery applications. In this dissertation, it has been demonstrated how the properties of monolayers play a crucial role in achieving a desired biological goal. In each case, the monolayer of AuNPs has been tailored using organic synthesis as a strategy to afford stable and biocompatible biological tools. These engineered AuNPs demonstrate numerous biomedical applications, including a controlled release of payload, cellular uptake, gene regulations, cytosolic delivery, and cytotoxicity

The biomacromolecule-nanoparticle interface

The wide variety of core materials, coupled with the ability to engineer their surface properties, make monolayer-protected nanoparticles (NPs) excellent scaffolds for targeting biomacromolecules. In this review, we focus on recent advances in NP-biomacromolecule interactions, highlighting the control of biomacromolecule structure and function through engineered interactions with NP surfaces

Charge Dependence of Ligand Release and Monolayer Stability of Gold Nanoparticles by Biogenic Thiols

The effect of surface charge on the stability of gold nanoparticles (AuNPs) to the biogenic thiols glutathione (GSH), dihydrolipoic acid (DHLA), and cysteine was quantified. It was observed that the rate of release of fluorescein-tagged ligand was determined by the surface charge of the AuNPs, with cationic particles much more labile than anionic analogues. This ability to tune stability is significant for the design of both delivery vehicles and intracellular probes

Green synthesis of silver nanoparticles in aloe vera plant extract prepared by a hydrothermal method and their synergistic antibacterial activity

Background There is worldwide interest in silver nanoparticles (AgNPs) synthesized by various chemical reactions for use in applications exploiting their antibacterial activity, even though these processes exhibit a broad range of toxicity in vertebrates and invertebrates alike. To avoid the chemical toxicity, biosynthesis (green synthesis) of metal nanoparticles is proposed as a cost-effective and environmental friendly alternative. Aloe vera leaf extract is a medicinal agent with multiple properties including an antibacterial effect. Moreover the constituents of aloe vera leaves include lignin, hemicellulose, and pectins which can be used in the reduction of silver ions to produce as AgNPs@aloe vera (AgNPs@AV) with antibacterial activity. Methods AgNPs were prepared by an eco-friendly hydrothermal method using an aloe vera plant extract solution as both a reducing and stabilizing agent. AgNPs@AV were characterized using XRD and SEM. Additionally, an agar well diffusion method was used to screen for antimicrobial activity. MIC and MBC were used to correlate the concentration of AgNPs@AV its bactericidal effect. SEM was used to investigate bacterial inactivation. Then the toxicity with human cells was investigated using an MTT assay. Results The synthesized AgNPs were crystalline with sizes of 70.70 ± 22-192.02 ± 53 nm as revealed using XRD and SEM. The sizes of AgNPs can be varied through alteration of times and temperatures used in their synthesis. These AgNPs were investigated for potential use as an antibacterial agent to inhibit pathogenic bacteria. Their antibacterial activity was tested on S. epidermidis and P. aeruginosa. The results showed that AgNPs had a high antibacterial which depended on their synthesis conditions, particularly when processed at 100 oC for 6 h and 200 oC for 12 h. The cytotoxicity of AgNPs was determined using human PBMCs revealing no obvious cytotoxicity. These results indicated that AgNPs@AV can be effectively utilized in pharmaceutical, biotechnological and biomedical applications. Discussion Aloe vera extract was processed using a green and facile method. This was a hydrothermal method to reduce silver nitrate to AgNPs@AV. Varying the hydrothermal temperature provided the fine spherical shaped nanoparticles. The size of the nanomaterial was affected by its thermal preparation. The particle size of AgNPs could be tuned by varying both time and temperature. A process using a pure AG phase could go to completion in 6 h at 200 oC, whereas reactions at lower temperatures required longer times. Moreover, the antibacterial effect of this hybrid nanomaterial was sufficient that it could be used to inhibit pathogenic bacteria since silver release was dependent upon its particle size. The high activity of the largest AgNPs might have resulted from a high concentration of aloe vera compounds incorporated into the AgNPs during hydrothermal synthesis

Photoregulation of Gold Nanoparticles Stabilized in a Diacetylenic Nanocapsule

The results of releasing a drug in a burst are unpredictable and one of the inherent drawbacks of using nanocarriers. Here, photoresponsive cationic gold nanoparticles to stabilize diacetylenic nanocapsules enabling photoregulated release of payloads are reported. The fabrication of these nanocapsules relied on an electrostatic interaction of a negatively charged diacetylenic core and a positively charged gold nanoparticle shell. Gold nanoparticles with photoresponsive ligands on their surfaces act as both hydrophobic core stabilizers and gatekeepers of the nanocapsules, while their polydiacetylene cores serve as hydrophobic drug carriers that can be tuned using UV irradiation. The morphology of nanocapsules was analyzed using TEM and dynamic light scattering. The resultant nanocapsules had a spherical shape with an average diameter of 152.9 ± 6.7 nm. Upon UV irradiation, the nanocapsules lost their integrity and an encapsulated model compound was released through diffusion. The release of a hydrophobic molecule was irradiation time dependent and thereby controllable. This light-triggered release provides an alternative strategy for controlled drug delivery

Light-Regulated Release of Entrapped Drugs from Photoresponsive Gold Nanoparticles

Release of a payload in a spatiotemporal fashion has a substantial impact on increasing therapeutic efficacy. In this work, a novel monolayer of gold nanoparticles (AuNPs) featuring light-responsive ligands was investigated as a potential drug carrier whose drug release can be triggered by UV light. Hydrophobic molecules were noncovalently entrapped in the compartments of its monolayers. Once irradiated with UV light, the dinitrobenzyl linker was cleaved, leading to release of the entrapped agent. AuNPs were characterized using UV spectrophotometry, TEM, and a zetasizer. A naturally occurring compound extracted from Goniothalamus elegans Ast was chosen as a hydrophobic model drug. Entrapment and release of dye were monitored using fluorimetry. The percent encapsulation of dye was of 13.53%. Entrapped dye can be released upon UV irradiation and can be regulated by changing irradiation time. Up to 83.95±2.2% entrapped dye can be released after irradiation for 20 minutes. In the absence of UV light, dye release was only 19.75%. For comparison purposes, AuNPs having no dinitrobenzyl groups showed a minimal release of 12.23% and 11.69% with and without UV light, respectively. This demonstrated an alternative strategy to encapsulate drugs using a noncovalent approach followed by their controlled release upon UV irradiation