Development and classification of RNA aptamers for therapeutic purposes: an updated review with emphasis on cancer.

Today, RNA aptamers are being considered promising theranostic tools against a wide variety of disorders. RNA aptamers can fold into complex shapes and bind to diverse nanostructures, macromolecules, cells, and viruses. It is possible to isolate RNA aptamers from a vast pool of nucleic acids via the Systematic Evolution of Ligands by Exponential Enrichment (SELEX) method. As therapeutics, aptamers have great potential because of their ability to bind to proteins and selectively limit their activities with negligible side effects. Several RNA aptamers with potential implications in cancer diagnosis are known to confer a great affinity for single-stranded DNA molecules, long non-coding RNAs, circulating tumor cells, vascular endothelial growth factors, and tissue and sera-derived exosomes in patients with different malignancies. Furthermore, clinical investigations have revealed the efficacy of RNA aptamer-based agents in imaging modalities. This review seeks to deliver new insights into the development, classification, nanomerization, and modification of RNA aptamers, as well as their applications in cancer theranostics. The aptamers' mechanism of action and their interest to clinical trials as theranostic agents are also discussed.

Identification of Catecholamine Neurotransmitters Using a Fluorescent Electronic Tongue.

Catecholamine neurotransmitters, specifically, dopamine (DA), epinephrine (EP), and norepinephrine (NE), are known as substantial indicators of various neurological diseases. Developing rapid detection methods capable of simultaneously screening their concentrations is highly desired for early clinical diagnosis of such diseases. To this aim, we have designed an optical sensor array using three fluorescent dyes with distinct emission bands and have monitored variations in their emission profiles upon the addition of DA, EP, and NE in the presence of gold ions. Because of the different reducing power of catecholamines, differently sized gold nanoparticles (GNPs) with different levels of aggregation were generated, resulting in different amounts of spectral overlap between the absorption band of the in situ generated plasmonic GNPs and the emission bands of the fluorescent dyes. These energy-transfer-based fingerprint profiles were used to discriminate the neurotransmitters by applying pattern recognition methods including linear discriminant analysis (LDA) and artificial neural networks (ANN) and to determine their concentration using multiple linear regression (MLR). Our proposed array also showed a good performance in the discrimination of DA, EP, and NE in complex biological media such as human urine.

Ratiometric fluorescent nanoprobes for visual detection: Design principles and recent advances - A review.

Signal generation techniques for visual detection of analytes have received a great deal of attention in various sensing fields. These approaches are considered to be advantageous when instrumentation cannot be employed, such as for on-site assays, point-of-care tests, and he althcare diagnostics in resource-constrained areas. Amongst various visual detection approaches explored for non-invasive quantitative measurements, ratiometric fluorescence sensing has received particular attention as a potential method to overcome the limitations of intensity-based probes. This technique relies on changes in the intensity of two or more emission bands (induced by an analyte), resulting in an effective internal referencing which improves the sensitivity of the detection. The self-calibration, together with the unique optophysical properties of nanoparticles (NPs) have made the ratiometric fluorescent nanoprobes more sensitive and reliable, which in turn, can result in more precise visual detection of the analytes. Over the past few years, a vast number of ratiometric sensing probes using nanostructured fluorophores have been designed and reported for a wide variety of sensing, imaging, and biomedical applications. In this work, a review on the NP-based ratiometric fluorescent sensors has been presented to meticulously elucidate their development, advances and challenges. With a special emphasis on visual detection, the most important steps in the design of fluorescent ratiometric nanoprobes have been given and based on different classes of analytes, recent applications of fluorescent ratiometric nanoprobes have been summarized. The challenges for the future use of the technique investigated in this review have been also discussed.

Maternal exposure to silver nanoparticles are associated with behavioral abnormalities in adulthood: Role of mitochondria and innate immunity in developmental toxicity.

Silver nanoparticles (Ag-NPs) are currently used in a wide range of consumer products. Considering the small size of Ag-NPs, they are able to pass through variety of biological barriers and exert their effects. In this regard, the unique physicochemical properties of Ag-NPs along with its high application in the industry have raised concerns about their negative effects on human health. Therefore, it investigated whether prenatal exposure to low doses of Ag-NPs is able to induce any abnormality in the cognitive and behavioral performance of adult offspring. We gavaged pregnant NMRI mice with, 1) Deionized water as vehicle, 2) Ag-NPs 10 nm (0.26 mg/kg/day), 3) Ag-NPs 30 nm (0.26 mg/kg/day), and 4) AgNO3 (0.26 mg/kg/day) from gestational day (GD) 0 until delivery day. At the postnatal day (PD) 1, our results showed that high concentration of silver is present in the brain of pups. Further, we observed mitochondrial dysfunction and upregulation of the genes relevant to innate immune system in the brain. At PD 60, results revealed that prenatal exposure to Ag-NPs provoked severe cognitive and behavioral abnormalities in male offspring. In addition, we found that prenatal exposure to Ag-NPs was associated with abnormal mitochondrial function and significant up-regulation of the genes relevant to innate immunity in the brain. Although the Ag-NPs have been considered as safe compounds at low doses, our results indicate that prenatal exposure to low doses of Ag-NPs is able to induce behavioral and cognitive abnormalities in adulthood. Also, we found that these effects are at least partly associated with hippocampal mitochondrial dysfunction and the activation of sterile inflammation during early stages of life.

Nanoparticle-based optical sensor arrays.

As in many other methods that have integrated nanoparticles (NPs), the chemical nose/tongue strategy has also progressed greatly since the entrance of NPs into this field. The fascinating tunable physicochemical properties of NPs have made them powerful candidates for array-based sensing platforms and have enabled the development of real-time, sensitive and portable systems that are able to target complex mixtures of analytes. In particular, the unique optical properties of NPs have a key role in providing promising array-based sensing approaches. This review will describe the main aspects and processes of most common NP-based optical sensor arrays. The fundamental steps in the design of a sensor array together with details of each step would be provided. The review begins with the principles of optical sensor arrays and presents the concept of cross-reactivity as the main criterion in the selection of sensing elements. Changes in the absorption and emission properties of the assembled sensing elements are categorized into two main classes of optical signals (colorimetric and fluorometric). Popular chemometric methods used for analyzing the data acquired by a sensor array have also been briefly introduced. On the basis of the objective and the desired application, different types of plasmonic and fluorescent NP that possess unique opto-physical properties have been presented as available choices in the design of sensing elements. The vast number of applications of NP-based optical sensor arrays published throughout the literature have then been reviewed according to their mechanism of interaction and the type of optical signal. Finally, the remaining challenges and future directions in this topic have been highlighted.

Effect of Crude Venom of Odonthobuthus doriae Scorpion in Cell Culture using Ion Channel Modulators.

Scorpion venom toxicity is one of the major medical concerns from old years, due to its influence on human activities and health. From many years ago a lot of researches established to examine different aspects of venom toxicity and its effects on different organs. During these years researchers are doing more specific studies on the cytotoxicity of scorpion venom. In Iran, Odonthobuthus doriae, the yellow scorpion is one of the major threats based on its neuro toxicity and severe pathophysiologic effects and researchers tried to find the mechanism of these neuro toxic effects. The previous studies have shown that in isolated organs the yellow scorpion venom is affecting the ion channels. Also some studies showed that this venom has severe cytotoxic effects on the cell lines with many ion channels like nerve cell lines. In this study, the cytotoxic effect of the crude venom of O.doriae on the 1321N1 cell line (cancerous nerve cells) was studied. Primary cell cultured investigated in the presence of different ion channel blockers: Ouabain (1mmol as Na channel blocker), Nifedipin (100 µmol as Ca channel blocker), and TEA (40 mmol as K channel blocker) by MTT method. The result showed that the O.doriae crude venom has cytotoxic effect via Na channels.

Colorimetric Fingerprints of Gold Nanorods for Discriminating Catecholamine Neurotransmitters in Urine Samples.

Catecholamine neurotransmitters, generally including dopamine (DA), epinephrine (EP) and norepinephrine (NE) are known as substantial indicators of various neurological diseases. Simultaneous detection of these compounds and their metabolites is highly recommended in early clinical diagnosis. To this aim, in the present contribution, a high performance colorimetric sensor array has been proposed for the detection and discrimination of catecholamines based on their reducing ability to deposit silver on the surface of gold nanorods (AuNRs). The amassed silver nanoshell led to a blue shift in the longitudinal localized surface plasmon resonance (LSPR) peak of AuNRs, creating a unique pattern for each of the neurotransmitters. Hierarchical cluster analysis (HCA) and linear discriminate analysis (LDA) pattern recognition techniques were employed to identify DA, EP and NE. The proposed colorimetric array is able to differentiate among individual neurotransmitters as well as their mixtures, successfully. Finally, it was shown that the sensor array can identify these neurotransmitters in human urine samples.