Coating an adenovirus with functionalized gold nanoparticles favors uptake, intracellular trafficking and anti-cancer therapeutic efficacy.

Adenoviral (Ad) vectors have proven to be important tools for gene and cell therapy, although some issues still need to be addressed, such as undesired interactions with blood components and off-target sequestration that ultimately hamper efficacy. In the past years, several organic and inorganic materials have been developed to reduce immunogenicity and improve biodistribution of Ad vectors. Here we investigated the influence of the functionalization of 14 nm PEGylated gold nanoparticles (AuNPs) with quaternary ammonium groups and an arginine-glycine-aspartic acid (RGD)-motif on the uptake and biodistribution of Ad vectors.

Intracellular Delivery of Biologically-Active Fungal Metabolite Gliotoxin Using Magnetic Nanoparticles.

Gliotoxin (GT), a secondary metabolite produced by Aspergillus molds, has been proposed as a potential anti-tumor agent. Here we have developed a nanoparticle approach to enhance delivery of GT in tumor cells and establish a basis for its potential use as therapeutical drug. GT bound to magnetic nanoparticles (MNPs) retained a high anti-tumor activity, correlating with efficient intracellular delivery, which was increased in the presence of glucose.

Correction: Gold nanoparticle coatings as efficient adenovirus carriers to non-infectable stem cells.

[This corrects the article DOI: 10.1039/C8RA09088B.].

Gold nanoparticle coatings as efficient adenovirus carriers to non-infectable stem cells.

Mesenchymal stem cells (MSCs) are adult pluripotent cells with the plasticity to be converted into different cell types. Their self-renewal capacity, relative ease of isolation, expansion and inherent migration to tumors, make them perfect candidates for cell therapy against cancer. However, MSCs are notoriously refractory to adenoviral infection, mainly because CAR (Coxsackie-Adenovirus Receptor) expression is absent or downregulated.

Portable low-cost instrumentation for monitoring Rayleigh scattering from chemical sensors based on metallic nanoparticles.

Using a Hg(II) sensor based on the aggregation of gold nanoparticles as a model system, we evaluated the performance of two portable low-cost devices that monitor the wavelength-ratiometric resonance Rayleigh scattering signal of the chemical sensor upon white-LED illumination. The first device uses two optical filter-photodiode combinations to detect scattered light while the second employs a novel ultra-compact (grating-free) spectral sensor. Results show that the response of the Hg(II) sensor monitored with these devices is comparable to that measured using a high-end benchtop scanning spectrofluorometer.

Highly sensitive ratiometric quantification of cyanide in water with gold nanoparticles via Resonance Rayleigh Scattering.

A highly sensitive and selective ratiometric sensor for the quantification of cyanide (CN) in aqueous samples has been developed using spherical gold nanoparticles (AuNPs) stabilized by polysorbate 40 (PS-40). Three different AuNP sizes (14, 40 and 80nm mean diameters) were used to evaluate the response of the sensor using both colorimetric and Resonance Rayleigh Scattering (RRS) detection schemes. The best results were obtained for the sensor using 40nm AuNPs, for which the limits of detection (LODs) were found to be 100nmolL in a benchtop instrument and 500nmolL by the naked eye, values well below the maximum acceptable level for drinking water (1.

Gold nanoparticle-siRNA mediated oncogene knockdown at RNA and protein level, with associated gene effects.

Aims: RNAi is a powerful tool for gene silencing that can be used to reduce undesirable overexpression of oncogenes as a novel form of cancer treatment. However, when using RNAi as a therapeutic tool there is potential for associated gene effects. This study aimed to utilize gold nanoparticles to deliver siRNA into HeLa cells.

RNAi-based glyconanoparticles trigger apoptotic pathways for in vitro and in vivo enhanced cancer-cell killing.

Gold glyconanoparticles (GlycoNPs) are full of promise in areas like biomedicine, biotechnology and materials science due to their amazing physical, chemical and biological properties. Here, siRNA GlycoNPs (AuNP@PEG@Glucose@siRNA) in comparison with PEGylated GlycoNPs (AuNP@PEG@Glucose) were applied in vitro to a luciferase-CMT/167 adenocarcinoma cancer cell line and in vivo via intratracheal instillation directly into the lungs of B6 albino mice grafted with luciferase-CMT/167 adenocarcinoma cells. siRNA GlycoNPs but not PEGylated GlycoNPs induced the expression of pro-apoptotic proteins such as Fas/CD95 and caspases 3 and 9 in CMT/167 adenocarcinoma cells in a dose dependent manner, independent of the inflammatory response, evaluated by bronchoalveolar lavage cell counting.

In vivo tumor targeting via nanoparticle-mediated therapeutic siRNA coupled to inflammatory response in lung cancer mouse models.

Up to now, functionalized gold nanoparticles have been optimized as an effective intracellular in vitro delivery vehicle for siRNAs to interfere with the expression of specific genes by selective targeting, and provide protection against nucleases. Few examples however of suchlike in vivo applications have been described so far. In this study, we report the use of siRNA/RGD gold nanoparticles capable of targeting tumor cells in a lung cancer syngeneic orthotopic murine model.

Imaging inward and outward trafficking of gold nanoparticles in whole animals.

Gold nanoparticles have emerged as novel safe and biocompatible tools for manifold applications, including biological imaging, clinical diagnostics, and therapeutics. The understanding of the mechanisms governing their interaction with living systems may help the design and development of new platforms for nanomedicine. Here we characterized the dynamics and kinetics of the events underlying the interaction of gold nanoparticles with a living organism, from the first interaction nanoparticle/cell membrane, to the intracellular trafficking and final extracellular clearance.

Design of multifunctional gold nanoparticles for in vitro and in vivo gene silencing.

Over the past decade, the capability of double-stranded RNAs to interfere with gene expression has driven new therapeutic approaches. Since small interfering RNA (siRNAs, 21 base pair double-stranded RNA) was shown to be able to elicit RNA interference (RNAi), efforts were directed toward the development of efficient delivery systems to preserve siRNA bioactivity throughout the delivery route, from the administration site to the target cell. Here we provide evidence of RNAi triggering, specifically silencing c-myc protooncogene, via the synthesis of a library of novel multifunctional gold nanoparticles (AuNPs).

Modification of plasmid DNA topology by 'histone-mimetic' gold nanoparticles.

Aims: Our aim is to explore whether gold nanoparticles (AuNPs) functionalized with a carboxylated polyethylene glycol (PEG) and protamine (AuNP@PEG@Prot) can modulate - enhance or restrain - DNA condensation, altering DNA conformation and inducing structural changes. Understanding how these nanoconjugates modulate DNA structure, size and shape of DNA condensates, and enable control over the resulting 3D structures is of major biological and therapeutic importance.

Materials & Methods: Citrate-AuNPs were covered with a dense layer of a hetero-functional octa(ethylene glycol) (SH-EG(8)-COOH).