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Purpose: Nanotechnology is one of the highly evolving fields of research having immense potential in various fields of healthcare sectors. The very advent of nanotechnology lies in its ability to serve as a targeted drug delivery system. The introduction of a new branch namely bionanotechnology has further expanded the scope, especially in the diagnostics and treatment of various diseases. Probiotics being a natural source with a plethora of beneficial properties have been investigated actively in recent days. Probiotics administered into the digestive system have been shown to promote gut health by increasing the microbial balance in the gut. However, the bioavailability of such administered probiotics remains a major concern. These probiotics are protected through microencapsulation techniques, which encapsulate them in small capsules. Several nanoparticles with varied dimensions, forms, surfaces and composites have recently been investigated for probiotic microencapsulation. This has been used for various therapeutic applications, such as drug delivery. This review gives an insight on various materials and strategies used for probiotic encapsulation. Design/methodology/approach: The main aim of this review is to give a perception of the different types of methods of probiotic encapsulation. Findings: This review implies the significance of probiotics and subsequent active release in the gastrointestinal system. Different sections of this review paper, on the other hand, may offer up new opportunities for comprehensive research in the field of microencapsulation for boosting probiotic viability and also talks about the various encapsulating materials that has been employed. Originality/value: This review emphasizes more perceptions about the ongoing and imminent techniques for encapsulating probiotics. [ABSTRACT FROM AUTHOR]

The significance of nanoparticles (NPs) in technological advancements is due to their adaptable characteristics and enhanced performance over their parent material. They are frequently synthesized by reducing metal ions into uncharged nanoparticles using hazardous reducing agents. However, there have been several initiatives in recent years to create green technology that uses natural resources instead of dangerous chemicals to produce nanoparticles. In green synthesis, biological methods are used for the synthesis of NPs because biological methods are eco-friendly, clean, safe, cost-effective, uncomplicated, and highly productive. Numerous biological organisms, such as bacteria, actinomycetes, fungi, algae, yeast, and plants, are used for the green synthesis of NPs. Additionally, this paper will discuss nanoparticles, including their types, traits, synthesis methods, applications, and prospects. [ABSTRACT FROM AUTHOR]

Background and purpose: The reciprocal translocation of the ABL gene from chromosome 9 to chromosome 22 near the BCR gene gives rise to chronic myelogenous leukemia (CML). The translocation results in forming the Philadelphia chromosome (BCR-ABL) tyrosine kinase. CML results in an increase in the number of white blood cells and alteration in tyrosine kinase expression. CML prognosis includes three stages, namely chronic, accelerated, and blast. The diagnosis method involves a CT scan, biopsy, and complete blood count. However, due to certain disadvantages, early diagnosis of CML is not possible by traditional methods. Nano­technology offers many advantages in diagnosing and treating cancer. Experimental approach: We searched PubMed, Scopus and Google Scholar using the keywords Philadelphia chromosome, bionano­technology, tyrosine kinase pathway, half-life, passive targeting, and organic and inorganic nanoparticles. The relevant papers and the classical papers in this field were selected to write about in this review. Key results: The sensitivity and specificity of an assay can be improved by nanoparticles. Utilizing this property, peptides, antibodies, aptamers, etc., in the form of nanoparticles, can be used to detect cancer at a much earlier stage. The half-life of the drug is also increased by nanoformulation. The nanoparticle-coated drugs can easily escape from the immune system. Conclusion: Depending on their type, nanoparticles can be categorized into organic, inorganic and hybrid. Each type has its advantages. Organic nanoparticles have good biocompatibility, inorganic nanoparticles increase the half-life of the drugs. In this review, we highlight the nanoparticles involved in treating CML.

The evaluation of engineered nanomaterial safety has been hindered by conflicting reports demonstrating differential degrees of toxicity with the same nanoparticles. The unique properties of these materials increase the likelihood that they will interfere with analytical techniques, which may contribute to this phenomenon. We tested the potential for: 1) nanoparticle intrinsic fluorescence/absorbance, 2) interactions between nanoparticles and assay components, and 3) the effects of adding both nanoparticles and analytes to an assay, to interfere with the accurate assessment of toxicity. Silicon, cadmium selenide, titanium dioxide, and helical rosette nanotubes each affected at least one of the six assays tested, resulting in either substantial over- or under-estimations of toxicity. Simulation of realistic assay conditions revealed that interference could not be predicted solely by interactions between nanoparticles and assay components. Moreover, the nature and degree of interference cannot be predicted solely based on our current understanding of nanomaterial behaviour. A literature survey indicated that ca. 95% of papers from 2010 using biochemical techniques to assess nanotoxicity did not account for potential interference of nanoparticles, and this number had not substantially improved in 2012. We provide guidance on avoiding and/or controlling for such interference to improve the accuracy of nanotoxicity assessments. [ABSTRACT FROM AUTHOR]

In this paper we show that hydroxyapatite nanoparticles (NP) can not only act as a chaperon (by imparting thermostability) but can serve as a synthetic enhancer of activity of an isolated extracellular pectate lyase (APL) with low native state activity. The purified enzyme (an attenuated strain of Macrophomina phaseolina) showed feeble activity at 50°C and pH 5.6. However, on addition of 10.5 µg/ml of hydroxyapatite nanoparticles (NP), APL activity increased 27.7 fold with a 51 fold increase in half-life at a temperature of 90°C as compared to untreated APL. The chaperon like activity of NP was evident from entropy–enthalpy compensation profile of APL. The upper critical temperature for such compensation was elevated from 50°C to 90°C in presence of NP. This dual role of NP in enhancing activity and conferring thermostability to a functionally impaired enzyme is reported for the first time. [ABSTRACT FROM AUTHOR]

Functional nanomaterials have recently attracted strong interest from the biology community, not only as potential drug delivery vehicles or diagnostic tools, but also as optical nanomaterials. This is illustrated by the explosion of publications in the field with more than 2,000 publications in the last 2 years (4,000 papers since 2000; from ISI Web of Knowledge, 'nanoparticle and cell' hit). Such a publication boom in this novel interdisciplinary field has resulted in papers of unequal standard, partly because it is challenging to assemble the required expertise in chemistry, physics, and biology in a single team. As an extreme example, several papers published in physical chemistry journals claim intracellular delivery of nanoparticles, but show pictures of cells that are, to the expert biologist, evidently dead (and therefore permeable). To attain proper cellular applications using nanomaterials, it is critical not only to achieve efficient delivery in healthy cells, but also to control the intracellular availability and the fate of the nanomaterial. This is still an open challenge that will only be met by innovative delivery methods combined with rigorous and quantitative characterization of the uptake and the fate of the nanoparticles. This review mainly focuses on gold nanoparticles and discusses the various approaches to nanoparticle delivery, including surface chemical modifications and several methods used to facilitate cellular uptake and endosomal escape. We will also review the main detection methods and how their optimum use can inform about intracellular localization, efficiency of delivery, and integrity of the surface capping. [ABSTRACT FROM AUTHOR]

Endosseous titanium (Ti) implant failure due to poor biocompatibility of implant surface remains a major problem for osseointegration. Improving the topography of Ti surface may enhance osseointegration, however, the mechanism remains unknown. To investigate the effect of modified Ti surface on osteogenesis, we loaded rapamycin (RA) onto nano-hydroxyapatite (HAp) coated Ti surface which was acid-etched, alkali-heated and HAp coated sequentially. Sodium hyaluronate (SH) was employed as an intermediate layer for the load of RA, and a steady release rate of RA was maintained. Cell vitality of MC3T3-E1 was assessed by MTT. Osteogenesis of MC3T3-E1 on this modified Ti surface was evaluated by alkaline phosphatase (ALP) activity, mineralization and related osteogenesis genes osteocalcin (OCN), osteopontin (OPN), Collagen-I and Runx2. The result revealed that RA/SH-loaded nano-HAp Ti surface was innocent for cell vitality and even more beneficial for cell osteogenesis in vitro. Furthermore, osteogenesis of MC3T3-E1 showed significant association with the mammalian target of rapamycin (mTOR) phosphorylation by RA, which required further study about the mechanism. The approach to this modified Ti surface presented in this paper has high research value for the development of Ti-based implant. [ABSTRACT FROM AUTHOR]

Neurotensin-polyplex nanoparticles provide efficient gene transfection of nigral dopaminergic neurons when intracerebrally injected in preclinical trials of Parkinson's disease because they do not cross the blood–brain barrier (BBB). Therefore, this study aimed to open BBB with focused ultrasound (FUS) on the substantia nigra to attain systemic and intranasal transfections and evaluate its detrimental effect in rats. Systemically injected Evans Blue showed that a two-pulse FUS opened the nigral BBB. Accordingly, 35 μL of neurotensin-polyplex nanoparticles encompassing the green fluorescent protein plasmid (79.6 nm mean size and + 1.3 mV Zeta-potential) caused its expression in tyrosine hydroxylase(+) cells (dopaminergic neurons) of both substantiae nigrae upon delivery via internal carotid artery, retro-orbital venous sinus, or nasal mucosa 30 min after FUS. The intracarotid delivery yielded the highest transgene expression, followed by intranasal and venous administration. However, FUS caused neuroinflammation displayed by infiltrated lymphocytes (positive to cluster of differentiation 45), activated microglia (positive to ionized calcium-binding adaptor molecule 1), neurotoxic A1 astrocytes (positive to glial fibrillary acidic protein and complement component 3), and neurotrophic A2 astrocytes (positive to glial fibrillary acidic protein and S100 calcium-binding protein A10), that ended 15 days after FUS. Dopaminergic neurons and axonal projections decreased but recuperated basal values on day 15 after transfection, correlating with a decrease and recovery of locomotor behavior. In conclusion, FUS caused transient neuroinflammation and reversible neuronal affection but allowed systemic and intranasal transfection of dopaminergic neurons in both substantiae nigrae. Therefore, FUS could advance neurotensin-polyplex nanotechnology to clinical trials for Parkinson's disease. [ABSTRACT FROM AUTHOR]

Chao Gao,1,* Yan Liu,2,* Ting-Lin Zhang,3,* Yi Luo,2,4,* Jie Gao,3,* Jian-Jian Chu,1 Bao-Feng Gong,1 Xiao-Han Chen,1 Tong Yin,1 Jian Zhang,2 You Yin1 1Department of Neurology, Second Affiliated Hospital (Shanghai Changzheng Hospital) of Naval Medical University, Shanghai, People’s Republic of China; 2Department of Clinical Pharmacy, Shanghai Jiao Tong University of Medicine, Shanghai, People’s Republic of China; 3Changhai Clinical Research Unit, Shanghai Changhai Hospital of Naval Medical University, Shanghai, People’s Republic of China; 4New Drug Discovery and Development, Biotheus Inc., Zhuhai, People’s Republic of China*These authors contributed equally to this workCorrespondence: You Yin; Jian Zhang, Tel +86-21-81885463 ; +86- 21-25077150, Email yinyou179@163.com; zhangjian@xinhuamed.com.cnAbstract: Current therapies for Alzheimer’s disease used in the clinic predominantly focus on reducing symptoms with limited capability to control disease progression; thus, novel drugs are urgently needed. While nanoparticles (liposomes, high-density lipoprotein-based nanoparticles) constructed with synthetic biomembranes have shown great potential in AD therapy due to their excellent biocompatibility, multifunctionality and ability to penetrate the BBB, nanoparticles derived from natural biomembranes (extracellular vesicles, cell membrane-based nanoparticles) display inherent biocompatibility, stability, homing ability and ability to penetrate the BBB, which may present a safer and more effective treatment for AD. In this paper, we reviewed the synthetic and natural biomembrane-derived nanoparticles that are used in AD therapy. The challenges associated with the clinical translation of biomembrane-derived nanoparticles and future perspectives are also discussed. Keywords: Alzheimer’s disease, nanoparticles, blood‒brain barrier, liposomes, bionanotechnology, neurodegenerative diseases

Stem cell transplantation has been expected to have various applications for regenerative medicine. However, in order to detect and trace the transplanted stem cells in the body, non-invasive and widely clinically available cell imaging technologies are required. In this paper, we focused on magnetic resonance (MR) imaging technology, and investigated whether the trimethylamino dextran-coated magnetic iron oxide nanoparticle -03 (TMADM-03), which was newly developed by our group, could be used for labeling adipose tissue-derived stem cells (ASCs) as a contrast agent. No cytotoxicity was observed in ASCs transduced with less than 100 µg-Fe/mL of TMADM-03 after a one hour transduction time. The transduction efficiency of TMADM-03 into ASCs was about four-fold more efficient than that of the alkali-treated dextran-coated magnetic iron oxide nanoparticle (ATDM), which is a major component of commercially available contrast agents such as ferucarbotran (Resovist), and the level of labeling was maintained for at least two weeks. In addition, the differentiation ability of ASCs labeled with TMADM-03 and their ability to produce cytokines such as hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF) and prostaglandin E2 (PGE2), were confirmed to be maintained. The ASCs labeled with TMADM-03 were transplanted into the left kidney capsule of a mouse. The labeled ASCs could be imaged with good contrast using a 1T MR imaging system. These data suggest that TMADM-03 can therefore be utilized as a contrast agent for the MR imaging of stem cells. [ABSTRACT FROM AUTHOR]

There is now a significant body of literature which reports that stripes form in the ligand shell of suitably functionalised Au nanoparticles. This stripe morphology has been proposed to strongly affect the physicochemical and biochemical properties of the particles. We critique the published evidence for striped nanoparticles in detail, with a particular focus on the interpretation of scanning tunnelling microscopy (STM) data (as this is the only technique which ostensibly provides direct evidence for the presence of stripes). Through a combination of an exhaustive re-analysis of the original data, in addition to new experimental measurements of a simple control sample comprising entirely unfunctionalised particles, we show that all of the STM evidence for striped nanoparticles published to date can instead be explained by a combination of well-known instrumental artefacts, or by issues with data acquisition/analysis protocols. We also critically re-examine the evidence for the presence of ligand stripes which has been claimed to have been found from transmission electron microscopy, nuclear magnetic resonance spectroscopy, small angle neutron scattering experiments, and computer simulations. Although these data can indeed be interpreted in terms of stripe formation, we show that the reported results can alternatively be explained as arising from a combination of instrumental artefacts and inadequate data analysis techniques. [ABSTRACT FROM AUTHOR]

The development of large-scale molecular computational networks is a promising approach to implementing logical decision making at the nanoscale, analogous to cellular signaling and regulatory cascades. DNA strands with catalytic activity (DNAzymes) are one means of systematically constructing molecular computation networks with inherent signal amplification. Linking multiple DNAzymes into a computational circuit requires the design of substrate molecules that allow a signal to be passed from one DNAzyme to another through programmed biochemical interactions. In this paper, we chronicle an iterative design process guided by biophysical and kinetic constraints on the desired reaction pathways and use the resulting substrate design to implement heterogeneous DNAzyme signaling cascades. A key aspect of our design process is the use of secondary structure in the substrate molecule to sequester a downstream effector sequence prior to cleavage by an upstream DNAzyme. Our goal was to develop a concrete substrate molecule design to achieve efficient signal propagation with maximal activation and minimal leakage. We have previously employed the resulting design to develop high-performance DNAzyme-based signaling systems with applications in pathogen detection and autonomous theranostics. [ABSTRACT FROM AUTHOR]

Silver nanoparticles (AgNPs) have attracted considerable attentions due to their unique properties and diverse applications. Although it has been reported that AgNPs have acute toxic effects on a variety of cultured mammalian cells and animal models, few studies have been conducted to evaluate the associated risk of AgNPs to human health at non-cytotoxic doses. In this paper, HepG2 cells were exposed to 10 nm and 100 nm AgNPs under non-cytotoxic conditions, and cell viability was assessed. At low doses, AgNPs displayed “hormesis” effects by accelerating cell proliferation. Further studies indicated that the activation states of MAPKs were differentially regulated in this process. Specifically, by increasing the expression of downstream genes, p38 MAPK played a central role in non-cytotoxic AgNP-induced hormesis. Moreover, the treatment of HepG2 cells with silver ions (Ag+) at the same dose levels induced distinct biological effects, suggesting that different intrinsic properties exist for AgNPs and Ag+. [ABSTRACT FROM AUTHOR]

Open vascular reconstructions frequently fail due to the development of recurrent disease or intimal hyperplasia (IH). This paper reports a novel drug delivery method using a rapamycin-loaded poly(lactide-co-glycolide) (PLGA) nanoparticles (NPs)/pluronic gel system that can be applied periadventitially around the carotid artery immediately following the open surgery. In vitro studies revealed that rapamycin dispersed in pluronic gel was rapidly released over 3 days whereas release of rapamycin from rapamycin-loaded PLGA NPs embedded in pluronic gel was more gradual over 4 weeks. In cultured rat vascular smooth muscle cells (SMCs), rapamycin-loaded NPs produced durable (14 days versus 3 days for free rapamycin) inhibition of phosphorylation of S6 kinase (S6K1), a downstream target in the mTOR pathway. In a rat balloon injury model, periadventitial delivery of rapamycin-loaded NPs produced inhibition of phospho-S6K1 14 days after balloon injury. Immunostaining revealed that rapamycin-loaded NPs reduced SMC proliferation at both 14 and 28 days whereas rapamycin alone suppressed proliferation at day 14 only. Moreover, rapamycin-loaded NPs sustainably suppressed IH for at least 28 days following treatment, whereas rapamycin alone produced suppression on day 14 with rebound of IH by day 28. Since rapamycin, PLGA, and pluronic gel have all been approved by the FDA for other human therapies, this drug delivery method could potentially be translated into human use quickly to prevent failure of open vascular reconstructions. [ABSTRACT FROM AUTHOR]

In this paper, we describe the effects of the combination of topographical, mechanical, chemical and intracellular electrical stimuli on a co-culture of fibroblasts and skeletal muscle cells. The co-culture was anisotropically grown onto an engineered micro-grooved (10 µm-wide grooves) polyacrylamide substrate, showing a precisely tuned Young’s modulus (∼ 14 kPa) and a small thickness (∼ 12 µm). We enhanced the co-culture properties through intracellular stimulation produced by piezoelectric nanostructures (i.e., boron nitride nanotubes) activated by ultrasounds, thus exploiting the ability of boron nitride nanotubes to convert outer mechanical waves (such as ultrasounds) in intracellular electrical stimuli, by exploiting the direct piezoelectric effect. We demonstrated that nanotubes were internalized by muscle cells and localized in both early and late endosomes, while they were not internalized by the underneath fibroblast layer. Muscle cell differentiation benefited from the synergic combination of topographical, mechanical, chemical and nanoparticle-based stimuli, showing good myotube development and alignment towards a preferential direction, as well as high expression of genes encoding key proteins for muscle contraction (i.e., actin and myosin). We also clarified the possible role of fibroblasts in this process, highlighting their response to the above mentioned physical stimuli in terms of gene expression and cytokine production. Finally, calcium imaging-based experiments demonstrated a higher functionality of the stimulated co-cultures. [ABSTRACT FROM AUTHOR]

Cationic polymers such as poly(amidoamine), PAMAM, dendrimers have been used to electrostatically complex siRNA molecules forming dendriplexes for enhancing the cytoplasmic delivery of the encapsulated cargo. However, excess PAMAM dendrimers is typically used to protect the loaded siRNA against enzymatic attack, which results in systemic toxicity that hinders the in vivo use of these particles. In this paper, we evaluate the ability of G4 (flexible) and G5 (rigid) dendrimers to complex model siRNA molecules at low +/− ratio of 2/1 upon incubation for 20 minutes and 24 hours. We examine the ability of the formed G4 and G5 dendriplexes to shield the loaded siRNA molecules and protect them from degradation by RNase V1 enzymes using atomic force microscopy (AFM). Results show that G4 and G5 dendrimers form similar hexagonal complexes upon incubation with siRNA molecules for 20 minutes with average full width of 43±19.3 nm and 62±8.3 at half the maximum height, respectively. AFM images show that these G4 and G5 dendriplexes were attacked by RNase V1 enzyme leading to degradation of the exposed RNA molecules that increased with the increase in incubation time. In comparison, incubating G4 and G5 dendrimers with siRNA for 24 hours led to the formation of large particles with average full width of 263±60 nm and 48.3±2.5 nm at half the maximum height, respectively. Both G4 and G5 dendriplexes had a dense central core that proved to shield the loaded RNA molecules from enzymatic attack for up to 60 minutes. These results show the feasibility of formulating G4 and G5 dendriplexes at a low N/P (+/−) ratio that can resist degradation by RNase enzymes, which reduces the risk of inducing non-specific toxicity when used in vivo. [ABSTRACT FROM AUTHOR]

Maxillary sinus augmentation is a commonly used procedure for the placement of dental implants. However, the use of natural and synthetic materials in this procedure has resulted in postoperative complications ranging from 12% to 38%. To address this issue, we developed a novel calcium deficient HA/β-TCP bone grafting nanomaterial using a two-step synthesis method with appropriate structural and chemical parameters for sinus lifting applications. We demonstrated that our nanomaterial exhibits high biocompatibility, enhances cell proliferation, and stimulates collagen expression. Furthermore, the degradation of β-TCP in our nanomaterial promotes blood clot formation, which supports cell aggregation and new bone growth. In a clinical trial involving eight cases, we observed the formation of compact bone tissue 8 months after the operation, allowing for the successful installation of dental implants without any early postoperative complications. Our results suggest that our novel bone grafting nanomaterial has the potential to improve the success rate of maxillary sinus augmentation procedures. [ABSTRACT FROM AUTHOR]

In vitro conservation and regeneration of potato germplasm is important in breeding programs. The objective of this study was to assess the combined effect of paclobutrazol (PAC) and silver nanoparticles (AgNPs) during reduced-growth conservation and their in vitro ability to regenerate S. tuberosum after conservation treatments. For the conservation system, apices were used as explants in Murashige and Skoog culture media with different combinations of PAC (0, 0.5, 1 and 2 mg L−1) and AgNPs (0, 50, 100 and 200 mg L−1). At six months of culture, plant length, number of lateral branches, number of leaves and roots, root length, stomatal density and total chlorophyll content were assessed. For regeneration, explants were internodes cultured in medium with only 2 mg L−1 benzyladenine (BA). At 60 d of culture, the response percentage, number of shoots per explant and shoot length were assessed. For in vitro conservation, the combination of 2 mg L−1 PAC and 50 mg L−1 AgNPs was the best treatment, whereas for in vitro regeneration, the highest number of shoots was in explants that were treated with 1 or 2 mg L−1 PAC with 50 mg L−1 AgNPs. In conclusion, PAC and AgNPs are alternatives for in vitro S. tuberosum conservation, and their evaluation in other species recalcitrant to the effect of ethylene is recommended. [ABSTRACT FROM AUTHOR]

The significance of nanoparticles (NPs) in technological advancements is due to their adaptable characteristics and enhanced performance over their parent material. They are frequently synthesized by reducing metal ions into uncharged nanoparticles using hazardous reducing agents. However, there have been several initiatives in recent years to create green technology that uses natural resources instead of dangerous chemicals to produce nanoparticles. In green synthesis, biological methods are used for the synthesis of NPs because biological methods are eco-friendly, clean, safe, cost-effective, uncomplicated, and highly productive. Numerous biological organisms, such as bacteria, actinomycetes, fungi, algae, yeast, and plants, are used for the green synthesis of NPs. Additionally, this paper will discuss nanoparticles, including their types, traits, synthesis methods, applications, and prospects.

We developed a narrowband magnetic particle imaging (MPI) system that uses third-harmonic signal detection and electrical scanning of the field free point (FFP). Comparing with mechanical scanning, we can decrease the measurement time significantly and increase the signal-to-noise ratio as well. For electrical scanning, we designed and constructed gradient and shift coils. The gradient coil consisting of four pieces of planar coils generated the gradient field with a field gradient of 0.4 T/m at a height of 25 mm from the coil surface. The FFP can be moved ±8 mm by supplying a current of ±6.6 A to the shift coil. Using the developed system, we detected two magnetic nanoparticle (MNP) samples located at a depth of 35 mm below the pickup coil with a spacing of 10 mm. By applying an excitation field of 1 mT at 22.75 kHz, we measured the third-harmonic signal from the MNP samples and obtained a contour map of the signal field in an area of 16 $\times$ 16 mm2. Then, we converted the field map into an MNP distribution using singular value decomposition method. It was shown that the spatial resolution of the reconstructed MNP distribution was improved compared with that of the measured contour map of the signal field. The spatial resolution for MNP detection in MNP distribution was 5 mm and two MNP samples were distinguished clearly. This result indicated that MPI using electrical scanning of the FFP was successfully performed. [ABSTRACT FROM AUTHOR]

Background: A recent report from the British Nuffield Council on Bioethics associated ‘emerging biotechnologies’ with a threefold challenge: 1) uncertainty about outcomes, 2) diverse public views on the values and implications attached to biotechnologies and 3) the possibility of creating radical changes regarding societal relations and practices. To address these challenges, leading international institutions stress the need for public involvement activities (PIAs). The objective of this study was to assess the state of PIA reports in the field of biomedical research. Methods: PIA reports were identified via a systematic literature search. Thematic text analysis was employed for data extraction. Results: After filtering, 35 public consultation and 11 public participation studies were included in this review. Analysis and synthesis of all 46 PIA studies resulted in 6 distinguishable PIA objectives and 37 corresponding PIA methods. Reports of outcome translation and PIA evaluation were found in 9 and 10 studies respectively (20% and 22%). The paper presents qualitative details. Discussion: The state of PIAs on biomedical research and innovation is characterized by a broad range of methods and awkward variation in the wording of objectives. Better comparability of PIAs might improve the translation of PIA findings into further policy development. PIA-specific reporting guidelines would help in this regard. The modest level of translation efforts is another pointer to the “deliberation to policy gap”. The results of this review could inform the design of new PIAs and future efforts to improve PIA comparability and outcome translation. [ABSTRACT FROM AUTHOR]

Abstract The major interest in nanoparticles as an application platform for biotechnology arises from their high surface-to-volume ratio. Iron oxide nanoparticles (IONPs) are particularly appealing due to their superparamagnetic behavior, which enables bioseparation using external magnetic fields. In order to design advanced biomaterials, improve binding capacities and develop innovative processing solutions, a thorough understanding of the factors governing organic-inorganic binding in solution is critical but has not yet been achieved, given the wide variety of chemical and physical influences. This paper offers a critical review of experimental studies of the interactions between low cost IONPs (bare iron oxides, silica-coated or easily-functionalized surfaces) and the main groups of biomolecules: proteins, lipids, nucleic acids and carbohydrates. Special attention is devoted to the driving forces and interdependencies responsible of interactions at the solid-liquid interface, to the unique structural characteristics of each biomolecular class, and to environmental conditions influencing adsorption. Furthermore, studies focusing on mixtures, which are still rare, but absolutely necessary to understand the biocorona, are also included. This review concludes with a discussion of future work needed to fill the gaps in knowledge of bio-nano interactions, seeking to improve nanoparticles’ targeting capabilities in complex systems, and to open the door for multipurpose recognition and bioseparation processes.

Aims: The matrix metalloproteinase (MMP) 2/9, also known as collagenases IV and gelatinases A/B, play a key role in cancer invasion and metastasis. However, the clinical trials of the MMP inhibitors (MMPIs) ended up with disappointing results. In this paper, we synthesized a gelatinase-responsive copolymer (mPEG-PCL) by inserting a gelatinase cleavable peptide (PVGLIG) between mPEG and PCL blocks of mPEG-PCL for anticancer drug delivery to make use of MMP2/9 as an intelligent target for drug delivery. Materials and Methods: mPEG-pep-PCL copolymer was synthesized via ring-opening copolymerization and double-amidation. To evaluate whether Nanoparticles (NPs) prepared from this copolymer are superior to NPs prepared from mPEG-PCL, NPs prepared from mPEG-PCL copolymer were used as positive control. Docetaxel-loading NPs using mPEG-pep-PCL and mPEG-PCL were prepared by nano-precipitation method, mentioned as Gel-NPs and Con-NPs, respectively. The morphologic changes of the NPs after treatment with gelatinases were observed macroscopically by spectrophotometer and microscopically by transmission electron microscopy (TEM) and atomic force microscopy (AFM). The cellular uptake amount and cytotoxicity of Gel-NPs and Con-NPs, respectively, in cell lines with different levels of gelatinase expression were studied. Moreover, the cytotoxicity study on the primary cancer cells isolated from pericardial fluids from a patient with late-stage lung cancer was conducted. Results: The Gel-NPs aggregated in response to gelatinases, which was confirmed macroscopically and microscopically. The cellular uptake amount of Gel-NPs was correlated with the level of gelatinases. The in vitro antitumor effect of Gel-NPs was also correlated with the level of gelatinases and was superior to Taxotere (commercially available docetaxel) as well as the Con-NPs. The cytotoxicity study on the primary lung cancer cells also confirmed the effectiveness of Gel-NPs. Conclusion: The results in this study preliminarily demonstrated the effectiveness of gelatinase-responsive targeting strategy and the prospect of this intelligent nano-drug delivery system though further studies are needed. [ABSTRACT FROM AUTHOR]

Light-sheet microscopy is a useful tool for performing biological investigations of thick samples and it has recently been demonstrated that it can also act as a suitable architecture for super-resolution imaging of thick biological samples by means of individual molecule localization. However, imaging in depth is still limited since it suffers from a reduction in image quality caused by scattering effects. This paper sets out to investigate the advantages of non-linear photoactivation implemented in a selective plane illumination configuration when imaging scattering samples. In particular, two-photon excitation is proven to improve imaging capabilities in terms of imaging depth and is expected to reduce light-sample interactions and sample photo-damage. Here, two-photon photoactivation is coupled to individual molecule localization methods based on light-sheet illumination (IML-SPIM), allowing super-resolution imaging of nuclear pH2AX in NB4 cells. [ABSTRACT FROM AUTHOR]

Abstract: We have reported the modification of biomolecule with nanomaterials. In this paper, the electrochemical response of different FAD-dependent enzymes at carbon nanomaterials modified electrode. The modified electrode also exhibits a promising enhanced electrocatalytic activity toward the oxidation of substrate. Different methods were used for fabrication of modified electrode. The presence of nanomaterials enhances the enzyme loading and stability. Cyclic voltammograms (CVs) were used for the determination of substrate and the apparent coefficient values for these compounds at different electrodes. Finally, we have studied the surface morphology of the modified electrode using scanning electron microscopy (SEM), which revealed that enzyme is coated on nanomaterials. [Copyright &y& Elsevier]

This review is directed to researchers interested in a new point of view with relevance to nano-biomedicine. The first part covers the uses and potential of diacetylene lipid, 1,2-bis(10,12-tricosadiynoyl)-sn-glycero-3-phosphocholine (DC8,9PC) in facilitating biological target recognition. The second part concentrates on the use of albumin as a "soft" coating for nanoparticles. This review makes comment on how fabricated nanoparticles will assist with future human health applications. [ABSTRACT FROM AUTHOR]

Zinc oxide (ZnO) nanostructures can be synthesized in nanoforms of spheres, rods, flowers, disks, walls, etc., among which nanoflowers have gained special attention due to their versatile biomedical and pollutant remedial applications in waste water and air. ZnO nanoflowers have an ultrasmall size with a huge surface area to volume ratio due to their hexagonal petal structures which render them superior compared to the nanoparticles of other shapes. The ZnO nanoflowers have bandgap energy equivalent to a semiconductor that makes them have unique photophysical properties. We have used the appropriate keywords in Google Scholar and PubMed to obtain the recent publications related to our topic. We have selected the relevant papers and utilized them to write this review. The different methods of synthesis of ZnO nanoflowers are chemical vapor deposition, facile hydrothermal, thermal evaporation, chemical reduction, bio route of synthesis, and solvothermal method, etc. which are mentioned in this review. ZnO nanoparticles are used in paints, cosmetics, and other products due to their high photocatalytic activity. The different applications of ZnO nanoflowers in the diagnosis of disease biomarkers, biosensors, catalysts, and the therapeutic process along with wastewater remediation and gas sensing applications will be discussed in this review.

In order to increase their sustainability, antimicrobial renewable molecules are fundamental additions to consumer goods. Rosmarinic acid is extracted from several terrestrial plants and represents an effective anti-microbial agent. Ulvan, extracted from algae, is an anti-microbial polysaccharide. The present review is dedicated to discussing the sources and the extraction methodologies for obtaining rosmarinic acid and ulvan. Moreover, the preparation of bioanosystems, integrating the two molecules with organic or inorganic substrates, are reviewed as methodologies to increase their effectiveness and stability. Finally, the possibility of preparing functional biomaterials and anti-microbial final products is discussed, considering scientific literature. The performed analysis indicated that the production of both molecules is not yet performed with mature industrial technologies. Nevertheless, both molecules could potentially be used in the packaging, biomedical, pharmaceutical, cosmetic, sanitary and personal care sectors, despite some research being required for developing functional materials with specific properties to pave the way for many more applications. [ABSTRACT FROM AUTHOR]

Nucleotides ratcheted through the biomolecular pores of nanopore sequencers generate raw picoamperage currents, which are segmented into step-current level signals representing the nucleotide sequence. These ‘squiggles’ are a noisy, distorted representation of the underlying true stepped current levels due to experimental and algorithmic factors. We were interested in developing a simulation model to support a white-box approach to identify common distortions, rather than relying on commonly used black box neural network techniques for basecalling nanopore signals. Dynamic time warped-space averaging (DTWA) techniques can generate a consensus from multiple noisy signals without introducing key feature distortions that occur with standard averaging. As a preprocessing tool, DTWA could provide cleaner and more accurate current signals for direct RNA or DNA analysis tools. However, DTWA approaches need modification to take advantage of the a-priori knowledge regarding a common, underlying gold-standard RNA / DNA sequence. Using experimental data, we derive a simulation model to provide known squiggle distortion signals to assist in validating the performance of analysis tools such as DTWA. Simulation models were evaluated by comparing mocked and experimental squiggle characteristics from one Enolase mRNA squiggle group produced by an Oxford MinION nanopore sequencer, and cross-validated using other Enolase, Sequin R1_71_1 and Sequin R2_55_3 mRNA studies. New techniques identified high inserted but low deleted base rates, generating consistent x1.7 squiggle event to base called ratios. Similar probability density and cumulative distribution functions, PDF and CDF, were found across all studies. Experimental PDFs were not the normal distributions expected if squiggle distortion arose from segmentation algorithm artefacts, or through individual nucleotides randomly interacting with individual nanopores. Matching experimental and mocked CDFs required the assumption that there are unique features associated with individual raw-current data streams. Z-normalized signal-to-noise ratios suggest intrinsic sensor limitations being responsible for half the gold standard and noisy squiggle DTW differences. [ABSTRACT FROM AUTHOR]

A biosensor can sense biological elements after interaction with the recognition element. The signal produced due to interaction of the analyte with its biochemical element is transduced by a transducer and detected by appropriate modes. The miniaturization of these biosensors at the nano level using nanostructures as a platform for sensing the analyte or its detection is called a nanobiosensor. Several biological elements can be detected like nucleic acids, enzymes, antibodies, microorganisms, toxins, cells etc. with high specificity. This mini review focuses on the different types of nanobiosensors based on the type of analyte and the type of transducer used for detection. The different types of fluorescence based design of biosensors are also discussed along with the metal enhanced fluorescence based nanobiosensors. The application of biosensors towards the diagnosis of various diseases, targeted drug delivery and imaging is also discussed. [ABSTRACT FROM AUTHOR]

Successful disinfection alongside complete endodontic tissue regeneration and revascularization are the most desired clinical outcomes of regenerative endodontics. Despite reported clinical successes, significant limitations to the current regenerative endodontic procedure (REP) have been elucidated. To improve the current REP, an antibiotics and nitric oxide (NO) releasing biomimetic nanomatrix gel was developed. The study evaluates antibacterial effects of an antibiotics and NO releasing biomimetic nanomatrix gel on multispecies endodontic bacteria. Antibiotics, ciprofloxacin (CF) and metronidazole (MN) were mixed and encapsulated within the NO releasing biomimetic nanomatrix gel. The gel was synthesized and self-assembled from peptide amphiphiles containing various functional groups. Antibacterial effects of the antibiotics and NO releasing biomimetic nanomatrix gel were evaluated using bacterial viability assays involving endodontic microorganisms including clinical samples. Pulp-dentin regeneration was evaluated via animal-model experiments. The antibiotics and NO releasing biomimetic nanomatrix gel demonstrated a concentration dependent antibacterial effect. In addition, NO alone demonstrated a concentration dependent antibacterial effect on endodontic microorganism. An in vivo analysis demonstrated the antibiotics and NO releasing biomimetic nanomatrix gel promoted tooth revascularization with maturation of root canals. An optimal concentration of and NO releasing nanomatrix gel is suggested for its potential as a root treatment material for REP and an appropriate protocol for human trials. Further investigation is required to obtain a larger sample size and decide upon ideal growth factor incorporation. [ABSTRACT FROM AUTHOR]

The protozoan parasite Leishmania causes leishmaniasis; a spectrum of diseases of which there are an estimated 1 million new cases each year. Current treatments are toxic, expensive, difficult to administer, and resistance to them is emerging. New therapeutics are urgently needed, however, screening the infective amastigote form of the parasite is challenging. Only certain species can be differentiated into axenic amastigotes, and compound activity against these does not always correlate with efficacy against the parasite in its intracellular niche. Methods used to assess compound efficacy on intracellular amastigotes often rely on microscopy-based assays. These are laborious, require specialist equipment and can only determine parasite burden, not parasite viability. We have addressed this clear need in the anti-leishmanial drug discovery process by producing a transgenic L. mexicana cell line that expresses the luciferase NanoLuc-PEST. We tested the sensitivity and versatility of this transgenic strain, in comparison with strains expressing NanoLuc and the red-shifted firefly luciferase. We then compared the NanoLuc-PEST luciferase to the current methods in both axenic and intramacrophage amastigotes following treatment with a supralethal dose of Amphotericin B. NanoLuc-PEST was a more dynamic indicator of cell viability due to its high turnover rate and high signal:background ratio. This, coupled with its sensitivity in the intramacrophage assay, led us to validate the NanoLuc-PEST expressing cell line using the MMV Pathogen Box in a two-step process: i) identify hits against axenic amastigotes, ii) screen these hits using our bioluminescence-based intramacrophage assay. The data obtained from this highlights the potential of compounds active against M. tuberculosis to be re-purposed for use against Leishmania. Our transgenic L. mexicana cell line is therefore a highly sensitive and dynamic system suitable for Leishmania drug discovery in axenic and intramacrophage amastigote models. [ABSTRACT FROM AUTHOR]

Parametric separation of carbon nanotubes, especially based on their length is a challenge for a number of nano-tech researchers. We demonstrate a method to combine bio-conjugation, SDS-PAGE, and silver staining in order to separate carbon nanotubes on the basis of length. Egg-white lysozyme, conjugated covalently onto the single-walled carbon nanotubes surfaces using carbodiimide method. The proposed conjugation of a biomolecule onto the carbon nanotubes surfaces is a novel idea and a significant step forward for creating an indicator for length-based carbon nanotubes separation. The conjugation step was followed by SDS-PAGE and the nanotube fragments were precisely visualized using silver staining. This high precision, inexpensive, rapid and simple separation method obviates the need for centrifugation, additional chemical analyses, and expensive spectroscopic techniques such as Raman spectroscopy to visualize carbon nanotube bands. In this method, we measured the length of nanotubes using different image analysis techniques which is based on a simplified hydrodynamic model. The method has high precision and resolution and is effective in separating the nanotubes by length which would be a valuable quality control tool for the manufacture of carbon nanotubes of specific lengths in bulk quantities. To this end, we were also able to measure the carbon nanotubes of different length, produced from different sonication time intervals. [ABSTRACT FROM AUTHOR]

Inflammatory breast cancer (IBC) is a rare and aggressive presentation of invasive breast cancer with a 62% to 68% 5-year survival rate. It is the most lethal form of breast cancer, and early recognition and treatment is important for patient survival. Like non-inflammatory breast cancer, IBC comprises multiple subtypes, with the triple-negative subtype being overrepresented. Although the current multimodality treatment regime of anthracycline- and taxane-based neoadjuvant therapy, surgery, and radiotherapy has improved the outcome of patients with triple-negative IBC, overall survival continues to be worse than in patients with non-inflammatory locally advanced breast cancer. Translation of new therapies into the clinics to successfully treat IBC has been poor, in part because of the lack of in vitro preclinical models that can accurately predict the response of the original tumor to therapy. We report the generation of a preclinical IBC patient-derived xenograft (PDX)-derived ex vivo (PDXEx) model and show that it closely replicates the tissue architecture of the original PDX tumor harvested from mice. The gene expression profile of our IBC PDXEx model had a high degree of correlation to that of the original tumor. This suggests that the process of generating the PDXEx model did not significantly alter the molecular signature of the original tumor. We demonstrate a high degree of similarity in drug response profile between a PDX mouse model and our PDXEx model generated from the same original PDX tumor tissue and treated with the same panel of drugs, indicating that our PDXEx model had high predictive value in identifying effective tumor-specific therapies. Finally, we used our PDXEx model as a platform for a robotic-based high-throughput drug screen of a 386-drug anti-cancer compound library. The top candidates identified from this drug screen all demonstrated greater therapeutic efficacy than the standard-of-care drugs used in the clinic to treat triple-negative IBC, doxorubicin and paclitaxel. Our PDXEx model is simple, and we are confident that it can be incorporated into a PDX mouse system for use as a first-pass screening platform. This will permit the identification of effective tumor-specific therapies with high predictive value in a resource-, time-, and cost-efficient manner. [ABSTRACT FROM AUTHOR]

Multiple experimental data demonstrated that the core gene network orchestrating self-renewal and differentiation of mouse embryonic stem cells involves activity of Oct4, Sox2 and Nanog genes by means of a number of positive feedback loops among them. However, recent studies indicated that the architecture of the core gene network should also incorporate negative Nanog autoregulation and might not include positive feedbacks from Nanog to Oct4 and Sox2. Thorough parametric analysis of the mathematical model based on this revisited core regulatory circuit identified that there are substantial changes in model dynamics occurred depending on the strength of Oct4 and Sox2 activation and molecular complexity of Nanog autorepression. The analysis showed the existence of four dynamical domains with different numbers of stable and unstable steady states. We hypothesize that these domains can constitute the checkpoints in a developmental progression from naïve to primed pluripotency and vice versa. During this transition, parametric conditions exist, which generate an oscillatory behavior of the system explaining heterogeneity in expression of pluripotent and differentiation factors in serum ESC cultures. Eventually, simulations showed that addition of positive feedbacks from Nanog to Oct4 and Sox2 leads mainly to increase of the parametric space for the naïve ESC state, in which pluripotency factors are strongly expressed while differentiation ones are repressed. [ABSTRACT FROM AUTHOR]

We consider a microfluidic molecular communication (MC) system, where the concentration-encoded molecular messages are transported via fluid flow-induced convection and diffusion, and detected by a surface-based MC receiver with ligand receptors placed at the bottom of the microfluidic channel. The overall system is a convection-diffusion-reaction system that can only be solved by numerical methods, e.g., finite element analysis (FEA). However, analytical models are key for the information and communication technology (ICT), as they enable an optimisation framework to develop advanced communication techniques, such as optimum detection methods and reliable transmission schemes. In this direction, we develop an analytical model to approximate the expected time course of bound receptor concentration, i.e., the received signal used to decode the transmitted messages. The model obviates the need for computationally expensive numerical methods by capturing the nonlinearities caused by laminar flow resulting in parabolic velocity profile, and finite number of ligand receptors leading to receiver saturation. The model also captures the effects of reactive surface depletion layer resulting from the mass transport limitations and moving reaction boundary originated from the passage of finite-duration molecular concentration pulse over the receiver surface. Based on the proposed model, we derive closed form analytical expressions that approximate the received pulse width, pulse delay and pulse amplitude, which can be used to optimize the system from an ICT perspective. We evaluate the accuracy of the proposed model by comparing model-based analytical results to the numerical results obtained by solving the exact system model with COMSOL Multiphysics. [ABSTRACT FROM AUTHOR]