Sub-cellular internalization and organ specific oral delivery of PABA nanoparticles by side chain variation

Background  

Organic nanomaterials having specific biological properties play important roles in in vivo delivery and clearance from the live cells. To develop orally deliverable nanomaterials for different biological applications, we have synthesized several fluorescently labelled, self-assembled PABA nanoparticles using possible acid side chain combinations and tested against insect and human cell lines and in vivo animal model. Flurophores attached to nanostructures help in rapid in vivo screening and tracking through complex tissues. The sub-cellular internalization mechanism of the conjugates was determined. A set of physio-chemical parameters of engineered nanoskeletons were also defined that is critical for preferred uptake in multiple organs of live Drosophila.     

The effect of calcium phosphate nanoparticles on hormone production and apoptosis in human granulosa cells

Objectives  

Although many nanomaterials are being used in academia, industry and daily life, there is little understanding about the effects of nanoparticles on the reproductive health of vertebral animals, including human beings. An experimental study was therefore performed here to explore the effect of calcium phosphate nanoparticles on both steroid hormone production and apoptosis in human ovarian granulosa cells.     

Interaction of silver nanoparticles with Tacaribe virus

Background  

Silver nanoparticles possess many unique properties that make them attractive for use in biological applications. Recently they received attention when it was shown that 10 nm silver nanoparticles were bactericidal, which is promising in light of the growing number of antibiotic resistant bacteria. An area that has been largely unexplored is the interaction of nanomaterials with viruses and the possible use of silver nanoparticles as an antiviral agent.     

Life cycle assessment at nanoscale: review and recommendations

Purpose  

The need for a systematic evaluation of the human and environmental impacts of engineered nanomaterials (ENMs) has been widely recognized, and a growing body of literature is available endorsing life cycle assessment (LCA) as a valid tool for the same. The purpose of this study is to evaluate how the nano-specific environmental assessments are being done within the existing framework of life cycle inventory and impact assessment and whether these frameworks are valid and/or whether they can be modified for nano-evaluations.     

A novel bacterial isolate Stenotrophomonas maltophilia as living factory for synthesis of gold nanoparticles

Background  

The synthesis of gold nanoparticles (GNPs) has received considerable attention with their potential applications in various life sciences related applications. Recently, there has been tremendous excitement in the study of nanoparticles synthesis by using some natural biological system, which has led to the development of various biomimetic approaches for the growth of advanced nanomaterials. In the present study, we have demonstrated the synthesis of gold nanoparticles by a novel bacterial strain isolated from a site near the famous gold mines in India. A promising mechanism for the biosynthesis of GNPs by this strain and their stabilization via charge capping was investigated.     

Biosafety of non-surface modified carbon nanocapsules as a potential alternative to carbon nanotubes for drug delivery purposes

Background

Carbon nanotubes (CNTs) have found wide success in circuitry, photovoltaics, and other applications. In contrast, several hurdles exist in using CNTs towards applications in drug delivery. Raw, non-modified CNTs are widely known for their toxicity. As such, many have attempted to reduce CNT toxicity for intravenous drug delivery purposes by post-process surface modification. Alternatively, a novel sphere-like carbon nanocapsule (CNC) developed by the arc-discharge method holds similar electric and thermal conductivities, as well as high strength. This study investigated the systemic toxicity and biocompatibility of different non-surface modified carbon nanomaterials in mice, including multi-walled carbon nanotubes (MWCNTs), single-walled carbon nanotubes (SWCNTs), carbon nanocapsules (CNCs), and C₆₀ fullerene (C₆₀). The retention of the nanomaterials and systemic effects after intravenous injections were studied.

Methodology and Principal Findings

MWCNTs, SWCNTs, CNCs, and C₆₀ were injected intravenously into FVB mice and then sacrificed for tissue section examination. Inflammatory cytokine levels were evaluated with ELISA. Mice receiving injection of MWCNTs or SWCNTs at 50 µg/g b.w. died while C₆₀ injected group survived at a 50% rate. Surprisingly, mortality rate of mice injected with CNCs was only at 10%. Tissue sections revealed that most carbon nanomaterials retained in the lung. Furthermore, serum and lung-tissue cytokine levels did not reveal any inflammatory response compared to those in mice receiving normal saline injection.

Conclusion

Carbon nanocapsules are more biocompatible than other carbon nanomaterials and are more suitable for intravenous drug delivery. These results indicate potential biomedical use of non-surface modified carbon allotrope. Additionally, functionalization of the carbon nanocapsules could further enhance dispersion and biocompatibility for intravenous injection.     

Framework for LCI modelling of releases of manufactured nanomaterials along their life cycle

Purpose

Numerous publications in the last years stressed the growing importance of nanotechnology in our society, highlighting both positive as well as in the negative topics. Life cycle assessment (LCA) is amongst the most established and best-developed tool in the area of product-related assessment. In order to use this tool in the area of nanotechnology, clear rules of how emissions of nanomaterials should be taken into account on the level of life cycle inventory (LCI) modelling are required—i.e. what elements and properties need to be reported for an emission of a nanomaterial. The objective of this paper is to describe such a framework for an adequate and comprehensive integration of releases of nanomaterials.

Methods

With a three-step method, additional properties are identified that are necessary for an adequate integration of releases of nanomaterials into LCA studies.

Result and discussion

In the first step, a comprehensive characterisation of the release of a nanomaterial is compiled—based on reviewing scientific publications, results from expert workshops and publications from public authorities and international organisations. In the second step, this comprehensive overview is refined to a list containing only those properties that are effectively relevant for LCA studies—i.e. properties that influence the impacts in the areas of human toxicity and ecotoxicity, respectively. For this, an academic approach is combined with a second, more practical, view point, resulting together in a prioritisation of this list of properties. Finally, in a third step, these findings are translated into the LCA language—by showing how such additional properties could be integrated into the current LCA data formats for a broader use by the LCA community.

Conclusions

As a compromise between scholarly knowledge and the (toxicological) reality, this paper presents a clear proposal of an LCI modelling framework for the integration of releases of nanomaterials in LCA studies. However, only the broad testing of this framework in various situations will show if the suggested simplifications and reductions keep the characterisation of releases of nanomaterials specific enough and/or if assessment is accurate enough. Therefore, a next step has to come from the impact assessment, by the development of characterisation factors as a function of size and shape of such releases.     

Toxicology of engineered nanomaterials: Focus on biocompatibility,biodistribution and biodegradation

Background

It is widely believed that engineered nanomaterials will be increasingly used in biomedical applications. However, before these novel materials can be safely applied in a clinical setting, their biocompatibility, biodistribution and biodegradation needs to be carefully assessed.

Scope of Review

There are a number of different classes of nanoparticles that hold promise for biomedical purposes. Here, we will focus on some of the most commonly studied nanomaterials: iron oxide nanoparticles, dendrimers, mesoporous silica particles, gold nanoparticles, and carbon nanotubes.

Major Conclusions

The mechanism of cellular uptake of nanoparticles and the biodistribution depend on the physico-chemical properties of the particles and in particular on their surface characteristics. Moreover, as particles are mainly recognized and engulfed by immune cells special attention should be paid to nano–immuno interactions. It is also important to use primary cells for testing of the biocompatibility of nanoparticles, as they are closer to the in vivo situation when compared to transformed cell lines.

General Significance

Understanding the unique characteristics of engineered nanomaterials and their interactions with biological systems is key to the safe implementation of these materials in novel biomedical diagnostics and therapeutics. This article is part of a Special Issue entitled Nanotechnologies - Emerging Applications in Biomedicine.     

Gum arabic modified Fe<Subscript>3</Subscript>O<Subscript>4</Subscript> nanoparticles cross linked with collagen for isolation of bacteria

Background  

Multifunctional magnetic nanoparticles are important class of materials in the field of nanobiotechnology, as it is an emerging area of research for material science and molecular biology researchers. One of the various methods to obtain multifunctional nanomaterials, molecular functionalization by attaching organic functional groups to nanomagnetic materials is an important technique. Recently, functionalized magnetic nanoparticles have been demonstrated to be useful in isolation/detection of dangerous pathogens (bacteria/viruses) for human life. Iron (Fe) based material especially FePt is used in the isolation of ultralow concentrations (< 10² cfu/ml) of bacteria in less time and it has been demonstrated that van-FePt may be used as an alternative fast detection technique with respect to conventional polymerase chain reaction (PCR) method. However, still further improved demonstrations are necessary with interest to biocompatibility and green chemistry. Herein, we report the synthesis of Fe₃O₄ nanoparticles by template medication and its application for the detection/isolation of S. aureus bacteria.     

Ions doped melanin nanoparticle as a multiple imaging agent

Background

Multimodal nanomaterials are useful for providing enhanced diagnostic information simultaneously for a variety of in vivo imaging methods. According to our research findings, these multimodal nanomaterials offer promising applications for cancer therapy.

Results

Melanin nanoparticles can be used as a platform imaging material and they can be simply produced by complexation with various imaging active ions. They are capable of specifically targeting epidermal growth factor receptor (EGFR)-expressing cancer cells by being anchored with a specific antibody. Ion-doped melanin nanoparticles were found to have high bioavailability with long-term stability in solution, without any cytotoxicity in both in vitro and in vivo systems.

Conclusion

By combining different imaging modalities with melanin particles, we can use the complexes to obtain faster diagnoses by computed tomography deep-body imaging and greater detailed pathological diagnostic information by magnetic resonance imaging. The ion-doped melanin nanoparticles also have applications for radio-diagnostic treatment and radio imaging-guided surgery, warranting further proof of concept experimental.

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Brief report: Lactobacillus bulgaricus GLB44 (Proviotic™) plus esomeprazole for Helicobacter pylori eradication: A pilot study

Background

Recent studies of Lactobacillus delbrueckii subsp. bulgaricus GLB44 plus a proton‐pump inhibitor (PPI) reported cures of more than 90% of patients with active Helicobacter pylori infections.

Aim

To confirm the high H. pylori cure rates reported previously.

Method

A pilot study was done in healthy H. pylori‐infected volunteers using 3‐gram sachet (3 billion cells) of L. delbrueckii GLB44 plus 22.3 mg of esomeprazole b.i.d., for 14 days. The result was determined by urea breath testing 4 weeks after therapy. Stopping rules required for ending enrollment if less than 3 of the first 10 subjects were cured.

Results

Nine subjects were entered and because all failed to achieve negative urea breath test, the stopping rule required the study to end.

Conclusion

We were unable to confirm reports of achieving a high H. pylori cure rate with L. delbrueckii GLB44 plus a PPI.     

Telomere length determined by the fluorescence in situ hybridisation distinguishes malignant and benign cells in cytological specimens

Background

Telomeres are tandem repeats of TTAGGG at the end of eukaryotic chromosomes that play a key role in preventing chromosomal instability. The aim of the present study is to determine telomere length using fluorescence in situ hybridisation (FISH) on cytological specimens.

Methods

Aspiration samples (n = 41) were smeared on glass slides and used for FISH.

Results

Telomere signal intensity was significantly lower in positive cases (cases with malignancy, n = 25) as compared to negative cases (cases without malignancy, n = 16), and the same was observed for centromere intensity. The difference in DAPI intensity was not statistically significant. The ratio of telomere to centromere intensity did not show a significant difference between positive and negative cases. There was no statistical difference in the signal intensities of aspiration samples from ascites or pleural effusion (n = 23) and endoscopic ultrasound‐guided FNA samples from the pancreas (n = 18).

Conclusions

The present study revealed that telomere length can be used as an indicator to distinguish malignant and benign cells in cytological specimens. This novel approach may help improve diagnosis for cancer patients.     

Unveiling the environmental drivers of intraspecific body size variation in terrestrial vertebrates

Aim

Whether intraspecific spatial patterns in body size are generalizable across species remains contentious, as well as the mechanisms underlying these patterns. Here we test several hypotheses explaining within-species body size variation in terrestrial vertebrates including the heat balance, seasonality, resource availability and water conservation hypotheses for ectotherms, and the heat conservation, heat dissipation, starvation resistance and resource availability hypotheses for endotherms.

Location

Global.

Time period

1970–2016.

Major taxa studied

Amphibians, reptiles, birds and mammals.

Methods

We collected 235,905 body size records for 2,229 species (amphibians = 36; reptiles = 81; birds = 1,545; mammals = 567) and performed a phylogenetic meta-analysis of intraspecific correlations between body size and environmental variables. We further tested whether correlations differ between migratory and non-migratory bird and mammal species, and between thermoregulating and thermoconforming ectotherms.

Results

For bird species, smaller intraspecific body size was associated with higher mean and maximum temperatures and lower resource seasonality. Size–environment relationships followed a similar pattern in resident and migratory birds, but the effect of resource availability on body size was slightly positive only for non-migratory birds. For mammals, we found that intraspecific body size was smaller with lower resource availability and seasonality, with this pattern being more evident in sedentary than migratory species. No clear size–environment relationships were found for reptiles and amphibians.

Main conclusions

Within-species body size variation across endotherms is explained by disparate underlying mechanisms for birds and mammals. Heat conservation (Bergmann's rule) and heat dissipation are the dominant processes explaining biogeographic intraspecific body size variation in birds, whereas in mammals, body size clines are mostly explained by the starvation resistance and resource availability hypotheses. Our findings contribute to a better understanding of the mechanisms behind species adaptations to the environment across their geographic distributions.     

Extensive evaluations of the cytotoxic effects of gold nanoparticles

Background

Many in vitro studies have revealed that the interference of dye molecules in traditional nanoparticle cytotoxicity assays results in controversial conclusions. The aim of this study is to establish an extensive and systematic method for evaluating biological effects of gold nanoparticles in mammalian cell lines.

Methods

We establish the cell-impedance measurement system, a label-free, real-time cell monitoring platform that measures electrical impedance, displaying results as cell index values, in a variety of mammalian cell lines. Cytotoxic effects of gold nanoparticles are also evaluated with traditional in vitro assays.

Results

Among the six cell lines, gold nanoparticles induce a dose-dependent suppression of cell growth with different levels of severity and the suppressive effect of gold nanoparticles was indirectly associated with their sizes and cellular uptake. Mechanistic studies revealed that the action of gold nanoparticles is mediated by apoptosis induction or cell cycle delay, depending on cell type and cellular context. Although redox signaling is often linked to the toxicity of nanoparticles, in this study, we found that gold nanoparticle-mediated reactive oxygen species generation was not sustained to notably modulate proteins involved in antioxidative defense system.

Conclusion

The cell-impedance measurement system, a dye-free, real-time screening platform, provides a reliable analysis for monitoring gold nanoparticle cytotoxicity in a variety of mammalian cell lines. Furthermore, gold nanoparticles induce cellular signaling and several sets of gene expression to modulate cellular physical processes.

General significance

The systematic approach, such as cell-impedance measurement, analyzing the toxicology of nanomaterials offers convincing evidence of the cytotoxicity of gold nanomaterials.     

Cortical beta EEG oscillations related to changes in muscle tone activity during sleep in spider monkey (Ateles geoffroyi)

Background

The physiological mechanisms that allow for sleeping in a vertical position, which is primordial for arboreal primates, have not been studied yet.

Methods

A non‐invasive polysomnographic study of 6 spider monkeys (Ateles geoffroyi) was conducted. The relative beta power of the motor cortex and its linear relation with muscle tone in the facial mentalis muscle and the abductor caudae medialis muscle of the tail during wakefulness and sleep stages were calculated.

Results

A strong negative linear relationship (r = ?.8, P = .03) was found between the relative power of the beta2 band in the left motor cortex and abductor caudae medialis muscle tone during delta sleep.

Conclusions

The left motor cortex, through beta2 band activity, interacts with abductor caudae medialis muscle tonicity during delta sleep. This interaction takes part in the mechanisms that regulate the sleep postures.     

Effect of menstrual cycle phase and hormonal treatments on evaluation of tubal patency in baboons

Background

We evaluated whether menstrual cycle phase influences the assessment of tubal patency by hysterosalpingography (HSG) in baboons.

Methods

Retrospective analysis of baseline tubal patency studies and serum estradiol (E₂) and progesterone (P4) values obtained from female baboons used as models for development of non‐surgical permanent contraception in women. The main outcome measure was bilateral tubal patency (BTP) in relationship with estradiol level.

Results

Female baboons (n = 110) underwent a single (n = 81), two (n = 26), or three (n = 3) HSG examinations. In 33/142 (23%) HSG examinations, one or both tubes showed functional occlusion (FO). The median E₂ in studies with BTP (49 pg/mL) was significantly higher than in those studies with FO (32 pg/mL, P = .005). Among 18 animals with repeat examinations where serum E₂ changed from <60 to ≥ 60 pg/mL, 13 results changed from FO to BTP (P = .0001). No sets showed a change from BTP to FO with an increase in estradiol.

Conclusion

In baboons, functional occlusion of the fallopian tube is associated with low estradiol levels, supporting a role for estrogen‐mediated relaxation of the utero‐tubal junction.     

Biosynthesis of silver nanoparticles using aqueous extract from the compactin producing fungal strain

In the present study, an eco-friendly process for the synthesis of nanomaterials using a fungus, Penicillium brevicompactum WA 2315 has been attempted. The fungus has been previously utilized for compactin production. Supernatant of seed culture was used for the biosynthesis of silver nanoparticles. The aqueous silver ions were reduced to silver metal nanoparticles when treated with the fungal supernatant. After 72 h of treatment, silver nanoparticles obtained were in the range of 23–105 nm as obtained from TEM. The nanoparticles were characterized by UV, FTIR, SEM, TEM and XRD. The use of supernatant of the seed media of the said fungus opens up the exciting possibility of rational strategy of biosynthesis of nanomaterials.     

Evaluation of DNA extraction methods for Bacillus anthracis spores isolated from spiked food samples

Aims

Nine commercial DNA extraction kits were evaluated for the isolation of DNA from 10‐fold serial dilutions of Bacillus anthracis spores using quantitative real‐time PCR (qPCR). The three kits determined by qPCR to yield the most sensitive and consistent detection (Epicenter MasterPure Gram Positive; MoBio PowerFood; ABI PrepSeq) were subsequently tested for their ability to isolate DNA from trace amounts of B. anthracis spores (approx. 6·5 × 10¹ and 1·3 × 10² CFU in 25 ml or 50 g of food sample) spiked into complex food samples including apple juice, ham, whole milk and bagged salad and recovered with immunomagnetic separation (IMS).

Methods and Results

The MasterPure kit effectively and consistently isolated DNA from low amounts of B. anthracis spores captured from food samples. Detection was achieved from apple juice, ham, whole milk and bagged salad from as few as 65 ± 14, 68 ± 8, 66 ± 4 and 52 ± 16 CFU, respectively, and IMS samples were demonstrated to be free of PCR inhibitors.

Conclusions

Detection of B. anthracis spores isolated from food by IMS differs substantially between commercial DNA extraction kits; however, sensitive results can be obtained with the MasterPure Gram Positive kit.

Significance and Impact of the Study

The extraction protocol identified herein combined with IMS is novel for B. anthracis and allows detection of low levels of B. anthracis spores from contaminated food samples.     

Screening of white‐rot fungi for bioprocessing of wheat straw into ruminant feed

Aim

In this study, the biological variation for improvement of the nutritive value of wheat straw by 12 Ceriporiopsis subvermispora, 10 Pleurotus eryngii and 10 Lentinula edodes strains was assessed. Screening of the best performing strains within each species was made based on the in vitro degradability of fungal‐treated wheat straw.

Methods and Results

Wheat straw was inoculated with each strain for 7 weeks of solid state fermentation. Weekly samples were evaluated for in vitro gas production (IVGP) in buffered rumen fluid for 72 h. Out of the 32 fungal strains studied, 17 strains showed a significantly higher (P < 0·05) IVGP compared to the control after 7 weeks (227·7 ml g^?1 OM). The three best Ceriporiopsis subvermispora strains showed a mean IVGP of 297·0 ml g^?1 OM, while the three best P. eryngii and L. edodes strains showed a mean IVGP of 257·8 and 291·5 ml g^?1 OM, respectively.

Conclusion

Ceriporiopsis subvermispora strains show an overall high potential to improve the ruminal degradability of wheat straw, followed by L. edodes and P. eryngii strains.

Significance and Impact of the Study

Large variation exists within and among different fungal species in the valorization of wheat straw, which offers opportunities to improve the fungal genotype by breeding.     

A Machine Learning Approach to Identify Clinical Trials Involving Nanodrugs and Nanodevices from ClinicalTrials.gov

Background

Clinical Trials (CTs) are essential for bridging the gap between experimental research on new drugs and their clinical application. Just like CTs for traditional drugs and biologics have helped accelerate the translation of biomedical findings into medical practice, CTs for nanodrugs and nanodevices could advance novel nanomaterials as agents for diagnosis and therapy. Although there is publicly available information about nanomedicine-related CTs, the online archiving of this information is carried out without adhering to criteria that discriminate between studies involving nanomaterials or nanotechnology-based processes (nano), and CTs that do not involve nanotechnology (non-nano). Finding out whether nanodrugs and nanodevices were involved in a study from CT summaries alone is a challenging task. At the time of writing, CTs archived in the well-known online registry ClinicalTrials.gov are not easily told apart as to whether they are nano or non-nano CTs—even when performed by domain experts, due to the lack of both a common definition for nanotechnology and of standards for reporting nanomedical experiments and results.

Methods

We propose a supervised learning approach for classifying CT summaries from ClinicalTrials.gov according to whether they fall into the nano or the non-nano categories. Our method involves several stages: i) extraction and manual annotation of CTs as nano vs. non-nano, ii) pre-processing and automatic classification, and iii) performance evaluation using several state-of-the-art classifiers under different transformations of the original dataset.

Results and Conclusions

The performance of the best automated classifier closely matches that of experts (AUC over 0.95), suggesting that it is feasible to automatically detect the presence of nanotechnology products in CT summaries with a high degree of accuracy. This can significantly speed up the process of finding whether reports on ClinicalTrials.gov might be relevant to a particular nanoparticle or nanodevice, which is essential to discover any precedents for nanotoxicity events or advantages for targeted drug therapy.