Mutagenic effects of gold nanoparticles induce aberrant phenotypes in Drosophila melanogaster

Abstract The peculiar physical/chemical characteristics of engineered nanomaterials have led to a rapid increase of nanotechnology-based applications in many fields. However, before exploiting their huge and wide potential, it is necessary to assess their effects upon interaction with living systems. In this context, the screening of nanomaterials to evaluate their possible toxicity and understand the underlying mechanisms currently represents a crucial opportunity to prevent severe harmful effects in the next future. In this work we show the in vivo toxicity of gold nanoparticles (Au NPs) in Drosophila melanogaster , highlighting significant genotoxic effects and, thus, revealing an unsettling aspect of the long-term outcome of the exposure to this nanomaterial. After the treatment with Au NPs, we observed dramatic phenotypic modifications in the subsequent generations of Drosophila , demonstrating their capability to induce mutagenic effects that may be transmitted to the descendants. Noteworthy, we were able to obtain the first nanomaterial-mutated organism, named NM-mut. Although these results sound alarming, they underline the importance of systematic and reliable toxicology characterizations of nanomaterials and the necessity of significant efforts by the nanoscience community in designing and testing suitable nanoscale surface engineering/coating to develop biocompatible nanomaterials with no hazardous effects for human health and environment. From the Clinical Editor While the clinical application of nanomedicine is still in its infancy, the rapid evolution of this field will undoubtedly result in a growing number of clinical trials and eventually in human applications. The interactions of nanoparticles with living organisms determine their toxicity and long-term safety, which must be properly understood prior to large-scale applications are considered. The paper by Dr. Pompa's team is the first ever demonstration of mutagenesis resulting in clearly observable phenotypic alterations and the generation of nano-mutants as a result of exposure to citrate-surfaced gold nanoparticles in drosophila. These groundbreaking results are alarming, but represent a true milestone in nanomedicine and serve as a a reminder and warning about the critical importance of "safety first" in biomedical science

Modular plastic chip for one-shot human papillomavirus diagnostic analysis.

In this article, we report the design and development of a plastic modular chip suitable for one-shot human papillomavirus (HPV) diagnostics, namely detection of the viral presence and relative genotyping, by two sequential steps performed directly on the same device. The device is composed of two modular and disposable plastic units that can be assembled or used separately. The first module is represented by a polydimethylsiloxane (PDMS) microreactor that is exploited for real-time polymerase chain reaction (PCR) and, thus, is suitable for detecting the presence of virus. The second unit is a PDMS microwell array that allows virus genotyping by a colorimetric assay, based on DNA hybridization technology developed on plastic, requiring simple inspection by the naked eye. The two modules can be easily coupled to reusable hardware, enabling the heating/cooling processes and the real-time detection of HPV. By coupling real-time assay and colorimetric genotyping on the same chip, the assembled device may provide a low-cost tool for HPV diagnostics, thereby favoring the prediction of cancer risk in patients

Water-repellent cellulose fiber networks with multifunctional properties.

We demonstrate a simple but highly efficient technique to introduce multifunctional properties to cellulose fiber networks by wetting them with ethyl-cyanoacrylate monomer solutions containing various suspended organic submicrometer particles or inorganic nanoparticles. Solutions can be applied on cellulosic surfaces by simple solution casting techniques or by dip coating, both being suitable for large area applications. Immediately after solvent evaporation, ethyl-cyanoacrylate starts cross-linking around cellulose fibers under ambient conditions because of naturally occurring surface hydroxyl groups and adsorbed moisture, encapsulating them with a hydrophobic polymer shell. Furthermore, by dispersing various functional particles in the monomer solutions, hydrophobic ethyl-cyanoacrylate nanocomposites with desired functionalities can be formed around the cellulose fibers. To exhibit the versatility of the method, cellulose sheets were functionalized with different ethyl-cyanoacrylate nanocomposite shells..

Concentration-Dependent, Size-Independent Toxicity of Citrate Capped AuNPs in Drosophila melanogaster

The expected potential benefits promised by nanotechnology in various fields have led to a rapid increase of the presence of engineered nanomaterials in a high number of commercial goods. This is generating increasing questions about possible risks for human health and environment, due to the lack of an in-depth assessment of the physical/chemical factors responsible for their toxic effects. In this work, we evaluated the toxicity of monodisperse citrate-capped gold nanoparticles (AuNPs) of different sizes (5, 15, 40, and 80 nm) in the model organism Drosophila melanogaster, upon ingestion. To properly evaluate and distinguish the possible dose- and/or size-dependent toxicity of the AuNPs, we performed a thorough assessment of their biological effects, using two different dose-metrics. In the first approach, we kept constant the total surface area of the differently sized AuNPs (Total Exposed Surface area approach, TES), while, in the second approach, we used the same number concentration of the four different sizes of AuNPs (Total Number of Nanoparticles approach, TNN). We observed a significant AuNPs-induced toxicity in vivo, namely a strong reduction of Drosophila lifespan and fertility performance, presence of DNA fragmentation, as well as a significant modification in the expression levels of genes involved in stress responses, DNA damage recognition and apoptosis pathway. Interestingly, we found that, within the investigated experimental conditions, the toxic effects in the exposed organisms were directly related to the concentration of the AuNPs administered, irrespective of their size

USE OF HIGH SURFACE NANOFIBROUS MATERIALS IN MEDICINE

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A general mechanism for intracellular toxicity of metal-containing nanoparticles

The assessment of the risks exerted by nanoparticles is a key challenge for academic, industrial, and regulatory communities worldwide. Experimental evidence points towards significant toxicity for a range of nanoparticles both in vitro and in vivo. Worldwide efforts aim at uncovering the underlying mechanisms for this toxicity. Here, we show that the intracellular ion release elicited by the acidic conditions of the lysosomal cellular compartment - where particles are abundantly internalized - is responsible for the cascading events associated with nanoparticles-induced intracellular toxicity. We call this mechanism a "lysosome-enhanced Trojan horse effect" since, in the case of nanoparticles, the protective cellular machinery designed to degrade foreign objects is actually responsible for their toxicity. To test our hypothesis, we compare the toxicity of similar gold particles whose main difference is in the internalization pathways. We show that particles known to pass directly through cell membranes become more toxic when modified so as to be mostly internalized by endocytosis. Furthermore, using experiments with chelating and lysosomotropic agents, we found that the toxicity mechanism for different metal containing NPs (such as metallic, metal oxide, and semiconductor NPs) is mainly associated with the release of the corresponding toxic ions. Finally, we show that particles unable to release toxic ions (such as stably coated NPs, or diamond and silica NPs) are not harmful to intracellular environments

Grouping of orally ingested silica nanomaterials via use of an integrated approach to testing and assessment to streamline risk assessment

Abstract Background Nanomaterials can exist in different nanoforms (NFs). Their grouping may be supported by the formulation of hypotheses which can be interrogated via integrated approaches to testing and assessment (IATA). IATAs are decision trees that guide the user through tiered testing strategies (TTS) to collect the required evidence needed to accept or reject a grouping hypothesis. In the present paper, we investigated the applicability of IATAs for ingested NFs using a case study that includes different silicon dioxide, SiO2 NFs. Two oral grouping hypotheses addressing local and systemic toxicity were identified relevant for the grouping of these NFs and verified through the application of oral IATAs. Following different Tier 1 and/or Tier 2 in vitro methods of the TTS (i.e., in vitro dissolution, barrier integrity and inflammation assays), we generated the NF datasets. Furthermore, similarity algorithms (e.g., Bayesian method and Cluster analysis) were utilized to identify similarities among the NFs and establish a provisional group(s). The grouping based on Tier 1 and/or Tier 2 testing was analyzed in relation to available Tier 3 in vivo data in order to verify if the read-across was possible and therefore support a grouping decision. Results The measurement of the dissolution rate of the silica NFs in the oro-gastrointestinal tract and in the lysosome identified them as gradually dissolving and biopersistent NFs. For the local toxicity to intestinal epithelium (e.g. cytotoxicity, membrane integrity and inflammation), the biological results of the gastrointestinal tract models indicate that all of the silica NFs were similar with respect to the lack of local toxicity and, therefore, belong to the same group; in vivo data (although limited) confirmed the lack of local toxicity of NFs. For systemic toxicity, Tier 1 data did not identify similarity across the NFs, with results across different decision nodes being inconsistent in providing homogeneous group(s). Moreover, the available Tier 3 in vivo data were also insufficient to support decisions based upon the obtained in vitro results and relating to the toxicity of the tested NFs. Conclusions The information generated by the tested oral IATAs can be effectively used for similarity assessment to support a grouping decision upon the application of a hypothesis related to toxicity in the gastrointestinal tract. The IATAs facilitated a structured data analysis and, by means of the expert’s interpretation, supported read-across with the available in vivo data. The IATAs also supported the users in decision making, for example, reducing the testing when the grouping was well supported by the evidence and/or moving forward to advanced testing (e.g., the use of more suitable cellular models or chronic exposure) to improve the confidence level of the data and obtain more focused information