Deciphering the expression dynamics of ANGPTL8 associated regulatory network in insulin resistance using formal modelling approaches

ANGPTL8 is a recently identified novel hormone which regulates both glucose and lipid metabolism. The increase in ANGPTL8 during compensatory insulin resistance has been recently reported to improve glucose tolerance and a part of cytoprotective metabolic circuit. However, the exact signalling entities and dynamics involved in this process have remained elusive. Therefore, the current study was conducted with a specific aim to model the regulation of ANGPTL8 with emphasis on its role in improving glucose tolerance during insulin resistance. The main contribution of this study is the construction of a discrete model (based on kinetic logic of René Thomas) and its equivalent Stochastic Petri Net model of ANGPTL8 associated Biological Regulatory Network (BRN) which can predict its dynamic behaviours. The predicted results of these models are in‐line with the previous experimental observations and provide comprehensive insights into the signalling dynamics of ANGPTL8 associated BRN. The authors’ results support the hypothesis that ANGPTL8 plays an important role in supplementing the insulin signalling pathway during insulin resistance and its loss can aggravate the pathogenic process by quickly leading towards Diabetes Mellitus. The results of this study have potential therapeutic implications for treatment of Diabetes Mellitus and are suggestive of its potential as a glucose‐lowering agent.Inspec keywords: molecular biophysics, biomembranes, diseases, stochastic processes, biochemistry, patient treatment, Petri nets, genetics, sugar, cellular biophysics, biology computingOther keywords: ANGPTL8 associated regulatory network, formal modelling approaches, lipid metabolism, compensatory insulin resistance, glucose tolerance, equivalent Stochastic Petri Net model, ANGPTL8 associated BRN     

Classification of drug molecules for oxidative stress signalling pathway

In humans, oxidative stress is involved in the development of diabetes, cancer, hypertension, Alzheimers’ disease, and heart failure. One of the mechanisms in the cellular defence against oxidative stress is the activation of the Nrf2‐antioxidant response element (ARE) signalling pathway. Computation of activity, efficacy, and potency score of ARE signalling pathway and to propose a multi‐level prediction scheme for the same is the main aim of the study as it contributes in a big amount to the improvement of oxidative stress in humans. Applying the process of knowledge discovery from data, required knowledge is gathered and then machine learning techniques are applied to propose a multi‐level scheme. The validation of the proposed scheme is done using the K‐fold cross‐validation method and an accuracy of 90% is achieved for prediction of activity score for ARE molecules which determine their power to refine oxidative stress.Inspec keywords: cancer, cellular biophysics, biochemistry, drugs, molecular biophysics, proteins, learning (artificial intelligence), medical computingOther keywords: oxidative stress, Nrf2‐antioxidant response element signalling pathway, ARE signalling pathway, diabetes, cancer, hypertension, Alzheimers’ disease, heart failure, machine learning techniques, K‐fold cross‐validation method, ARE molecules     

Chitosan nanoparticles loaded with aspirin and 5‐fluororacil enable synergistic antitumour activity through the modulation of NF‐κB/COX‐2 signalling pathway

Based on the enhancement of synergistic antitumour activity to treat cancer and the correlation between inflammation and carcinogenesis, the authors designed chitosan nanoparticles for co‐delivery of 5‐fluororacil (5‐Fu: an as anti‐cancer drug) and aspirin (a non‐steroidal anti‐inflammatory drug) and induced synergistic antitumour activity through the modulation of the nuclear factor kappa B (NF‐κB)/cyclooxygenase‐2 (COX‐2) signalling pathways. The results showed that aspirin at non‐cytotoxic concentrations synergistically sensitised hepatocellular carcinoma cells to 5‐Fu in vitro. It demonstrated that aspirin inhibited NF‐κB activation and suppressed NF‐κB regulated COX‐2 expression and prostaglandin E2 (PGE2) synthesis. Furthermore, the proposed results clearly indicated that the combination of 5‐Fu and aspirin by chitosan nanoparticles enhanced the intracellular concentration of drugs and exerted synergistic growth inhibition and apoptosis induction on hepatocellular carcinoma cells by suppressing NF‐κB activation and inhibition of expression of COX‐2.Inspec keywords: proteins, molecular biophysics, cellular biophysics, biomedical materials, cancer, nanoparticles, drug delivery systems, enzymes, tumours, nanomedicine, drugsOther keywords: chitosan nanoparticles, aspirin, 5‐fluororacil, synergistic antitumour activity, anticancer drug, nonsteroidal antiinflammatory drug, hepatocellular carcinoma cells, NF‐κB activation, NF‐κB regulated COX‐2 expression, PGE2, synergistic growth inhibition, apoptosis induction, prostaglandin E2 synthesis, intracellular concentration, noncytotoxic concentrations, NF‐κB‐cyclooxygenase‐2 signalling pathways, cyclooxygenase‐2, nuclear factor kappa B     

Small RNA‐mediated switch‐like regulation in bacterial quorum sensing

Quorum sensing (QS) is a signalling mechanism by which bacteria produce, release and then detect and respond to changes in their density and biosignals called autoinducers (AIs). There are multiple feedback loops in the QS system of Vibrio harveyi. However, how these feedback loops function to control signal processing remains unclear. In this study, the authors present a computational model for the switch‐like regulation of signal transduction by small regulatory RNA‐mediated QS based on intertwined network involving AIs, LuxO, LuxU, Qrr sRNAs and LuxR. In agreement with experimental observations, the model suggests that different feedbacks play critical roles in the switch‐like regulation. The authors results reveal that V. harveyi uses multiple feedbacks to precisely control signal transduction.Inspec keywords: biocommunications, biocontrol, biology computing, cellular biophysics, physiological models, RNAOther keywords: RNA‐mediated switch‐like regulation, bacterial quorum sensing, signaling mechanism, autoinducers, Vibrio harveyi, feedback loops function, signal processing control, switch‐like regulation     

Synthesis,stability, and in vitro oral cancer cell toxicity of human serum albumin stabilised gold nanoflowers

Gold nanoflowers (GNFs) prepared by reduction of HAuCl₄ by ascorbic acid were capped with human serum albumin (HSA) by either electrostatic or covalent attachment to prevent their self‐aggregation. Measurement of surface plasmon resonance absorbance changes under different stress conditions showed that GNFs stabilised by covalent attachment of HSA were more stable than those stabilised by electrostatic attachment. Cytotoxicity of the covalently conjugated GNF was also studied in cultured human oral cancer cell lines by measuring the metabolic activity via 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide assay.Inspec keywords: proteins, molecular biophysics, biomedical materials, reduction (chemical), gold, cellular biophysics, nanofabrication, biochemistry, surface plasmon resonance, cancer, nanomedicine, materials preparation, nanostructured materialsOther keywords: Au, human serum albumin stabilised gold nanoflowers, cytotoxicity, in vitro oral cancer cell toxicity, stress conditions, surface plasmon resonance absorbance, 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide assay, self‐aggregation, covalent attachment, electrostatic attachment, ascorbic acid, cultured human oral cancer cell lines     

System‐based strategies for p53 recovery

The authors have proposed a systems theory‐based novel drug design approach for the p53 pathway. The pathway is taken as a dynamic system represented by ordinary differential equations‐based mathematical model. Using control engineering practices, the system analysis and subsequent controller design is performed for the re‐activation of wild‐type p53. p53 revival is discussed for both modes of operation, i.e. the sustained and oscillatory. To define the problem in control system paradigm, modification in the existing mathematical model is performed to incorporate the effect of Nutlin. Attractor point analysis is carried out to select the suitable domain of attraction. A two‐loop negative feedback control strategy is devised to drag the system trajectories to the attractor point and to regulate cellular concentration of Nutlin, respectively. An integrated framework is constituted to incorporate the pharmacokinetic effects of Nutlin in the cancerous cells. Bifurcation analysis is also performed on the p53 model to see the conditions for p53 oscillation.Inspec keywords: proteins, tumours, cancer, cellular biophysics, molecular biophysics, molecular configurations, biochemistry, differential equations, closed loop systems, bifurcation, biology computingOther keywords: system‐based strategies, p53 recovery, systems theory‐based novel drug design approach, dynamic system, ordinary differential equations‐based mathematical model, control engineering practices, subsequent controller design, wild‐type p53, p53 revival, oscillatory, control system paradigm, mathematical model, Nutlin effect, attractor point analysis, domain‐of‐attraction, two‐loop negative feedback control strategy, cellular concentration, pharmacokinetic effects, cancerous cells, bifurcation analysis, p53 oscillation, anomalous cell     

Contribution of time delays to p53 oscillation in DNA damage response

Although the oscillatory dynamics of the p53 network have been extensively studied, the understanding of the mechanism of delay‐induced oscillations is still limited. In this paper, a comprehensive mathematical model of p53 network is studied, which contains two delayed negative feedback loops. By studying the model with and without explicit delays, the results indicate that the time delay of Mdm2 protein synthesis can well control the pulse shape but cannot induce p53 oscillation alone, while the time delay required for Wip1 protein synthesis induces a Hopf bifurcation to drive p53 oscillation. In addition, the synergy of the two delays will cause the p53 network to oscillate in advance, indicating that p53 begins the repair process earlier in the damaged cell. Furthermore, the stability and bifurcation of the model are addressed, which may highlight the role of time delay in p53 oscillations.Inspec keywords: proteins, cellular biophysics, DNA, molecular biophysics, biomolecular effects of radiation, bifurcation, physiological models, cellular effects of radiation, oscillations, geneticsOther keywords: highlight, time delay, delayed negative feedback loops, murine double minute 2, Wip1 protein synthesis, explicit delays, Mdm2 protein synthesis, p53 network     

Honokiol–camptothecin loaded graphene oxide nanoparticle towards combinatorial anti‐cancer drug delivery

Honokiol (HK) is a natural product isolated from the bark, cones, seeds and leaves of plants belonging to the genus Magnolia. It possesses anti‐cancer activity which can efficiently impede the growth and bring about apoptosis of a diversity of cancer cells. The major concerns of using HK are its poor solubility and lack of targeted drug delivery. In this study, a combinatorial drug is prepared by combining HK and camptothecin (CPT). Both CPT and HK belong to the Magnolian genus and induce apoptosis by cell cycle arrest at the S‐phase and G1 phase, respectively. The combinatorial drug thus synthesised was loaded onto a chitosan functionalised graphene oxide nanoparticles, predecorated with folic acid for site‐specific drug delivery. The CPT drug‐loaded nanocarrier was characterised by X‐ray diffractometer, scanning electron microscope, transmission electron microscope, UV–vis spectroscopy and fluorescence spectroscopy, atomic force microscopy. The antioxidant properties, haemolytic activity and anti‐inflammatory activities were analysed. The cellular toxicity was analysed by 3‐(4,5‐Dimethylthiazol‐2‐yl)‐2,5‐Diphenyltetrazolium Bromide (MTT assay) and Sulforhodamine B (SRB) assay against breast cancer (MCF‐7) cell lines.Inspec keywords: nanofabrication, cancer, nanoparticles, atomic force microscopy, graphene, scanning electron microscopy, cellular biophysics, toxicology, transmission electron microscopy, drug delivery systems, nanomedicine, tumours, solubilityOther keywords: targeted drug delivery, combinatorial drug, Magnolian genus, apoptosis, cell cycle, chitosan functionalised graphene oxide nanoparticles, site‐specific drug delivery, CPT drug‐loaded nanocarrier, transmission electron microscope, fluorescence spectroscopy, haemolytic activity, antiinflammatory activities, breast cancer cell lines, honokiol–camptothecin loaded graphene oxide nanoparticle, combinatorial anti‐cancer drug delivery, natural product, genus Magnolia, anticancer activity, cancer cells     

Functionalisation of Fe3 O4 nanoparticles by 2‐((pyrazol‐4‐yl) methylene) hydrazinecarbothioamide enhances the apoptosis of human breast cancer MCF‐7 cells

Cancer is a major cause of death. Thus, the incidence and mortality rate of cancer is globally important. Regarding vast problems caused by chemotherapy drugs, efforts have progressed to find new anti‐cancer drugs. Pyrazole derivatives are known as components with anti‐cancer properties. In here, Fe₃ O₄ nanoparticles were first functionalized with (3‐chloropropyl) trimethoxysilane, then 2‐((pyrazol‐4‐yl) methylene) hydrazinecarbothioamide (P) was anchored on the surface of magnetic nanoparticles (PL). The synthesized nano‐compounds were characterized using Fourier transform infrared spectroscopy, X‐ray diffraction, scanning electron microscopy, Zeta potential, dynamic light scattering, and energy‐dispersive x‐ray spectrometry analyses. The cytotoxicity effect was evaluated using MTT assay, apoptosis test by Flow cytometry, cell cycle analysis, Caspase‐3 activity assay and Hoechst staining on MCF‐7 cell line. The high toxicity for tumor cells and low toxicity on normal cells (MCF10A) was considered as an important feature (selectivity index, 10.9). Based on results, the IC50 for P and PL compounds were 157.80 and 131.84 μM/ml respectively. Moreover, apoptosis inducing, nuclear fragmentation, Caspase 3 activity and induction of cell rest in sub‐G1 and S phases, were also observed. The inhibitory effect of PL was significantly higher than P, which could be due to the high penetrability of Fe₃ O₄ nanoparticles.Inspec keywords: magnetic particles, drugs, nanomedicine, biochemistry, cancer, light scattering, scanning electron microscopy, molecular biophysics, iron compounds, electrokinetic effects, nanofabrication, tumours, X‐ray diffraction, cellular biophysics, nanoparticles, biomedical materials, toxicology, nanomagnetics, Fourier transform infrared spectra, enzymes, X‐ray chemical analysisOther keywords: anticancer properties, Fe₃ O₄ magnetic nanoparticles, (3‐chloropropyl) trimethoxysilane, energy‐dispersive X‐ray spectrometry, cell cycle analysis, MCF‐7 cell line, tumour cells, human breast cancer MCF‐7 cells, mortality rate, pyrazole derivatives, 2‐((pyrazol‐4‐yl) methylene) hydrazinecarbothioamide, chemotherapy drugs, heterocyclic components, nanocompounds, X‐ray diffraction, scanning electron microscopy, Zeta potential, dynamic light scattering, cytotoxicity effect, MTT assay, apoptosis test, caspase‐3 activity assay, Hoechst staining, MCF10A nontumourigenic cells, cell rest induction, nuclear fragmentation, Fe₃ O₄      

Systems analysis utilising pathway interactions identifies sonic hedgehog pathway as a primary biomarker and oncogenic target in hepatocellular carcinoma

The development and progression of cancer is associated with disruption of biological networks. Historically studies have identified sets of signature genes involved in events ultimately leading to the development of cancer. Identification of such sets does not indicate which biologic processes are oncogenic drivers and makes it difficult to identify key networks to target for interventions. Using a comprehensive, integrated computational approach, the authors identify the sonic hedgehog (SHH) pathway as the gene network that most significantly distinguishes tumour and tumour‐adjacent samples in human hepatocellular carcinoma (HCC). The analysis reveals that the SHH pathway is commonly activated in the tumour samples and its activity most significantly differentiates tumour from the non‐tumour samples. The authors experimentally validate these in silico findings in the same biologic material using Western blot analysis. This analysis reveals that the expression levels of SHH, phosphorylated cyclin B1, and CDK7 levels are much higher in most tumour tissues as compared to normal tissue. It is also shown that siRNA‐mediated silencing of SHH gene expression resulted in a significant reduction of cell proliferation in a liver cancer cell line, SNU449 indicating that SHH plays a major role in promoting cell proliferation in liver cancer. The SHH pathway is a key network underpinning HCC aetiology which may guide the development of interventions for this most common form of human liver cancer.Inspec keywords: bioinformatics, cancer, cellular biophysics, genetics, liver, molecular biophysics, RNA, systems analysis, tumoursOther keywords: biomedical informatics, human liver cancer, network underpinning HCC aetiology, liver cancer cell line, cell proliferation, SHH gene expression, siRNA‐mediated silencing, CDK7 levels, phosphorylated cyclin B1, Western blot analysis, in silico findings, SHH pathway, human hepatocellular carcinoma, tumour‐adjacent samples, gene network, integrated computational approach, oncogenic drivers, biologic processes, cancer development, biological networks, cancer progression, oncogenic target, primary biomarker, sonic hedgehog pathway, pathway interactions, systems analysis     

Architecture‐dependent robustness in a class of multiple positive feedback loops

Many types of multiple positive feedbacks with each having potentials to generate bistability exist extensively in natural, raising the question of why a particular architecture is present in a cell. In this study, the authors investigate multiple positive feedback loops across three classes: one‐loop class, two‐loop class and three‐loop class, where each class is composed of double positive feedback loop (DPFL) or double negative feedback loop (DNFL) or both. Through large‐scale sampling and robustness analysis, the authors find that for a given class, the homogeneous DPFL circuit (i.e. the coupled circuit that is composed of only DPFLs) is more robust than all the other circuits in generating bistable behaviour. In addition, stochastic simulation shows that the low stable state is more robust than the high stable state in homogeneous DPFL whereas the high‐stable state is more robust than the low‐stable state in homogeneous DNFL circuits. It was argued that this investigation provides insight into the relationship between robustness and network architecture.Inspec keywords: cellular biophysics, feedback, sampling methods, stochastic processesOther keywords: network architecture, low stable state, stochastic simulation, bistable behaviour, homogeneous DPFL circuit, robustness analysis, large‐scale sampling, DNFL, double negative feedback loop, double positive feedback loop, three‐loop class, two‐loop class, one‐loop class, cell architecture, bistability, multiple positive feedback loops, architecture‐dependent robustness     

PEGylated zinc oxide nanoparticles induce apoptosis in pancreatic cancer cells through reactive oxygen species

In this study, the authors have successfully prepared the polyethylene glycol (PEG)‐coated zinc oxide nanoparticles (ZNPs) and studied its effect in pancreatic cancer cells. The authors have observed a nanosized particle with spherical shape. In this study, the authors have demonstrated the cytotoxic effect of ZNP and PZNP in PANC1 cells. To be specific, PZNP was more cytotoxic compared to that of ZNP in PANC1 cancer cells. The authors have further showed that apoptosis is the main mode of cytotoxic activity. It is worth noting that PEGylation of ZNP did not decrease the cell killing activity of zinc particles, whereas it further increases its anticancer effect in the pancreatic cancer cells. The authors have observed a significant upregulation of proapoptotic BAX while expression of antiapoptotic Bcl‐2 was significantly downregulated indicating the potent anticancer effect of zinc nanoparticles. Overall, PEGylation of ZNP could be an effective strategy to improve the stability, while at the same time, its anticancer activity could be enhanced for better therapeutic response.Inspec keywords: biomedical materials, drug delivery systems, tumours, toxicology, nanoparticles, cellular biophysics, drugs, nanomedicine, cancer, nanofabrication, zinc compounds, II‐VI semiconductorsOther keywords: pancreatic cancer cells, reactive oxygen species, polyethylene glycol‐coated zinc oxide nanoparticles, cytotoxic effect, cytotoxic activity, PEGylation, anticancer effect, PEGylated zinc oxide nanoparticle induce apoptosis, proapoptotic BAX upregulation, ZnO     

Comprehensive study of tumour single nucleotide polymorphism array data reveals significant driver aberrations and disrupted signalling pathways in human hepatocellular cancer

The authors describe an integrated method for analysing cancer driver aberrations and disrupted pathways by using tumour single nucleotide polymorphism (SNP) arrays. The authors new method adopts a novel statistical model to explicitly quantify the SNP signals, and therefore infers the genomic aberrations, including copy number alteration and loss of heterozygosity. Examination on the dilution series dataset shows that this method can correctly identify the genomic aberrations even with the existence of severe normal cell contamination in tumour sample. Furthermore, with the results of the aberration identification obtained from multiple tumour samples, a permutation‐based approach is proposed for identifying the statistically significant driver aberrations, which are further incorporated with the known signalling pathways for pathway enrichment analysis. By applying the approach to 286 hepatocellular tumour samples, they successfully uncover numerous driver aberration regions across the cancer genome, for example, chromosomes 4p and 5q, which harbour many known hepatocellular cancer related genes such as alpha‐fetoprotein (AFP) and ectodermal‐neural cortex (ENC1). In addition, they identify nine disrupted pathways that are highly enriched by the driver aberrations, including the systemic lupus erythematosus pathway, the vascular endothelial growth factor (VEGF) signalling pathway and so on. These results support the feasibility and the utility of the proposed method on the characterisation of the cancer genome and the downstream analysis of the driver aberrations and the disrupted signalling pathways.Inspec keywords: cancer, DNA, genetics, genomics, liver, molecular biophysics, molecular configurations, physiological models, polymorphism, statistical analysis, tumoursOther keywords: tumour single nucleotide polymorphism array data, disrupted signalling pathways, human hepatocellular cancer, cancer driver aberrations, statistical model, SNP signals, genomic aberrations, heterozygosity, dilution series dataset, normal cell contamination, permutation‐based approach, statistical significant driver aberrations, hepatocellular tumour samples, cancer genome, hepatocellular cancer related genes, systemic lupus erythematosus pathway, VEGF signalling pathway     

Phytofabrication of silver nanoparticles using Bacopa monnieri leaf extract and its antibacterial activity as well as oxidative stress‐induced apoptosis of lung cancer

The biological method for synthesis of silver nanoparticles (AgNPs) using Bacopa monneri leaves and its anti‐proliferation against human lung adenocarcinoma cell line (A549) was studied. The AgNPs synthesis was determined by an ultraviolet–visible spectrum and was confirmed primarily by the colour change and surface plasmon resonance was observed at 450 nm and its reduction of functional groups stretched in AgNPs was identified by Fourier transform infrared and the crystalline nature of AgNPs was confirmed by X‐ray diffraction. The structural morphology of the AgNPs was found to be spherical and polygonal shape and size (> 35 nm) were determined by field emission scanning electron microscopy analysis and its purity was identified by energy dispersive analysis of X‐rays (EDAX). A further, antibacterial activity of biosynthesised AgNPs against Gram negative and Gram positive bacteria was assessed. The cytotoxic effect of synthesised AgNPs was analysed against human lung adenocarcinoma cells by 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide assay. The GI₅₀ was found to be 20 µg/ml at 24 h incubation. The apoptosis cells containing condensate and marginalised chromatin stages were analysed by propidium iodide staining and DNA damage was observed in A549 treated cells. The present study strongly emphasised that the bioactive molecule‐coated AgNPs could have potential for biomedical applications and significant anticancer effects against human lung adenocarcinoma cells.Inspec keywords: antibacterial activity, biomedical materials, lung, cancer, oxidation, nanoparticles, silver, nanofabrication, nanomedicine, cellular biophysics, ultraviolet spectra, visible spectra, surface plasmon resonance, Fourier transform infrared spectra, X‐ray diffraction, particle size, field emission electron microscopy, scanning electron microscopy, X‐ray chemical analysis, microorganisms, toxicology, DNA, molecular biophysics, molecular configurationsOther keywords: silver nanoparticles, phytofabrication, Bacopa monnieri leaf extract, antibacterial activity, oxidative stress‐induced apoptosis, biological method, antiproliferation, human lung adenocarcinoma cell line A549, AgNPs synthesis, ultraviolet‐visible spectrum, colour change, surface plasmon resonance, stretched functional groups, Fourier transform infrared spectra, crystalline nature, X‐ray diffraction, geometric spherical shape, polygonal shape, field emission scanning electron microscopy analysis, EDAX, biosynthesised AgNPs, gram negative bacteria, gram positive bacteria, cytotoxic effect, 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide assay, incubation, apoptosis cells, condensate, marginalised chromatin stages, propidium iodide staining, DNA damage, A549 treated cells, bioactive molecule‐coated AgNPs, biomedical applications, anticancer effects, time 24 h, Ag     

Induction of extrinsic and intrinsic apoptosis in cervical cancer cells by Momordica dioica mediated gold nanoparticles

Bio‐fabrication of gold nanoparticles (AuNPs) has several advantages like biocompatibility, less toxicity, and eco‐friendly in nature over their chemical and physical methods. Currently, the authors fabricated AuNPs using aqueous root extract of Momordica dioica (M. dioica) and explored their anticancer application with mechanistic approaches. Different biophysical techniques such as UV–visible spectroscopy, Fourier transform infrared, X‐ray diffraction, transmission electron microscopy, selected area electron diffraction, and dynamic light scattering were employed for AuNPs characterisation. The synthesised AuNPs were mono‐dispersed, crystalline in nature, anionic surface (−23.9 mV), and spherical particle of an average diameter of 9.4 nm. In addition, the AuNPs were stable in buffers solutions and also biocompatible towards normal human cells (human vascular endothelial cells and human lung cells). The AuNPs were exhibited anticancer activity against different cancer cell lines such as human breast cancer cells, human cervical cancer cells (HeLa) and human lung cancer cells. Further, the pro‐apoptotic genes such as Bcl₂ were down‐regulated and BAX, Caspase‐3, −8, and −9 were up‐regulated in HeLa cells as compared to untreated cells. Annexin‐V‐FITC assay results showed that the AuNPs were induced apoptosis by accumulation of intracellular reactive oxygen species. To their knowledge, this is the first report on the synthesis of bioactive metal nanoparticles from M. dioica and it may open up new avenues in therapeutic applications.Inspec keywords: nanomedicine, tumours, lung, visible spectra, drug delivery systems, cancer, transmission electron microscopy, biomedical materials, molecular biophysics, light scattering, toxicology, electron diffraction, X‐ray diffraction, ultraviolet spectra, biomembranes, drugs, gold, biochemistry, particle size, cellular biophysics, nanoparticles, nanofabrication, Fourier transform infrared spectraOther keywords: extrinsic apoptosis, intrinsic apoptosis, mediated gold nanoparticles, biofabrication, physical methods, biophysical techniques, UV‐visible spectroscopy, X‐ray diffraction, transmission electron microscopy, selected area electron diffraction, AuNPs characterisation, normal human cells, human vascular endothelial cells, cancer cell lines, human breast cancer cells, human cervical cancer cells, human lung cancer cells, HeLa cells, untreated cells, bioactive metal nanoparticles, Momordica dioica mediated gold nanoparticles, Fourier transform infrared spectra, proapoptotic genes, Bcl₂ , BAX, Caspase‐3, Caspase‐9, Caspase‐8, Annexin‐V‐FITC assay, intracellular reactive oxygen species, therapeutic applications, voltage ‐23.9 mV, size 9.4 nm, Au     

Redox/pH dual stimuli‐responsive ZnO QDs‐gated mesoporous silica nanoparticles as carriers in cancer therapy

New drug delivery system (ZnO@CMS) of the redox and pH dual‐stimuli responsive based on colloidal mesoporous silica nanoparticles (CMS) has been designed, in which zinc oxide quantum dots (ZnO QDs) as a capping agent was conjugated on the surface of nanoparticles by amide bonds. The release behaviour of doxorubicin (DOX) as the model drug from ZnO@CMS (ZnO@CMS‐DOX) indicated the redox and pH dual‐stimuli responsive properties due to the acidic dissolution of ZnO QDs and cleavage of the disulphide bonds. The haemolysis and bovine serum albumin adsorption assays showed that the modification of ZnO QDs on the mesoporous silica nanoparticles modified by mercapto groups (CMS‐SH)(ZnO@CMS) had better biocompatibility compared to CMS‐SH. The cell viability and cellular uptake tests revealed that the ZnO@CMS might achieve the antitumour effect on cancer cells due to the cytotoxicity of ZnO QDs. Therefore, ZnO@CMS might be potential nanocarriers of the drug delivery system in cancer therapy. The in vivo evaluation of ZnO@CMS would be carried out in future work.Inspec keywords: biochemistry, nanomedicine, cellular biophysics, pH, toxicology, tumours, semiconductor quantum dots, proteins, colloids, II‐VI semiconductors, mesoporous materials, silicon compounds, oxidation, cancer, drug delivery systems, zinc compounds, adsorption, molecular biophysics, nanomagnetics, drugs, biomedical materials, nanofabrication, nanoparticles, nanoporous materialsOther keywords: cancer therapy, drug delivery system, amide bonds, haemolysis, bovine serum albumin adsorption assays, mercapto groups, cancer cells, cytotoxicity, antitumour effect, redox/pH dual stimuli‐responsive zinc oxide quantum dots‐gated colloidal mesoporous silica nanoparticles, ZnO, SiO₂      

PEG‐Citrate dendrimer second generation: is this a good carrier for imaging agents In Vitro and In Vivo ?

While cancer is the leading cause of human''s deaths worldwide, finding an imaging agent which can detect cancer tumours is needed for cancer diagnosis. In the present study, PEG‐citrate dendrimer‐G₂ was used as a nano‐carrier of FITC dye and Iohexol to help passive targeting and uptake of both imaging agents in cancer cells/tumour in vitro and in vivo. Dendrimer was synthesisedand the product characterised using LC‐MS, FT‐IR, DLS, ELS, AFM, and ¹ HNMR. After FITC loading into dendrimer, MTT was performed to determine the cytotoxicity of formulation on HEK‐293 and MCF‐7 cells. In vitro imaging using dendrimer‐FITC was done via fluorescent microscope thereafter. Moreover, CT imaging using Iohexol was employed to show the targeting nature and ability of the complex to use as imaging agent in vivo. Data yielded in this study corroborate the notion that the promised dendrimer was synthesised properly and had no toxicity along with FITC on normal cell. Furthermore, CT and fluorescent images showed the targeting nature and imaging ability of Iohexol/FITC loaded dendrimer in vitro and in vivo. Overall, results showed promising characteristics of the novel complexes using dendrimer‐G₂ both in vitro and in vivo.Inspec keywords: drug delivery systems, cellular biophysics, molecular biophysics, fluorescence, cancer, tumours, drugs, nanomedicine, biomedical materials, dyes, toxicologyOther keywords: imaging agent, cancer tumours, cancer diagnosis, PEG‐citrate dendrimer‐G, FITC dye, cancer cells, FITC loading, vitro imaging, dendrimer‐FITC, CT imaging, targeting nature, promised dendrimer, fluorescent images, imaging ability, Iohexol/FITC