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Tumor necrosis factor (TNF)-related apoptosis inducing ligand (TRAIL), known as a cytokine of the TNF superfamily, is considered a promising antitumor agent due to its ability to selectively induce apoptosis in a wide variety of cancer cells. However, failure of its successful translation into clinic has led to development of nano-based platforms aiming to improve TRAIL therapeutic efficacy. In this regard, we fabricated a novel TRAIL-S-layer fusion protein (S-TRAIL) conjugated with graphene quantum dots (GQDs) to benefit both the self-assembly of S-layer proteins, which leads to elevated TRAIL functional stability, and unique optical properties of GQDs. Noncovalent conjugation of biocompatible GQDs and soluble fusion protein was verified via UV–visible and fluorescence spectroscopy, size and ζ-potential measurements and transmission electron microscopy. The potential anticancer efficacy of the nanohybrid system on intrinsically resistant cells to TRAIL (HT-29 human colon carcinoma cells) was investigated by MTT assay and flow cytometry, which indicated about 80% apoptosis in cancer cells. These results highlight the potential of TRAIL as a therapeutic protein that can be extensively improved by taking advantage of nanotechnology and introduce S-TRAIL/GQD complex as a promising nanohybrid system in cancer treatment.

Gene therapy has become a promising remedy to treat disease by modifying the person's genes. The therapeutic potential of related tools such as CRISPR-Cas9 depends on the efficiency of delivery to the targeted cells. Numerous transfection reagents have been designed and lots of efforts have been devoted to develop carriers for this purpose. Therefore, the aim of the present study was to develop novel cholesterol-rich lipid-based nanoparticles to enhance transfection efficiency and serum stability. We constructed two-, three- and four-component cationic liposomes (CLs) to evaluate the combined effect of cholesterol domain and DOPE (dioleoyl phosphatidylethanolamine), a fusogenic lipid, and the PEG (polyethylene glycol) moiety location inside or outside of the cholesterol domain on transfection efficiency and other properties of the particle. Lipoplex formation and pDNA (plasmid DNA) entrapment were assessed by gel retardation assay at different N/P ratios (3, 5, 7). Physicochemical characteristics, cytotoxicity, serum stability and endosomal escape capability of the lipoplexes were studied and transfection potential was measured by firefly luciferase assay. Next, HEK293 cell line stably expressing GFP was utilized to demonstrate the editing of a reporter through Cas9 and sgRNA plasmids delivery by the selected CL formula, which showed the highest transfection efficiency. Among the designed CLs, the four-component formula [DOTAP (1,2-dioleoyl-3-trimethylammoniumpropane)/DOPE/cholesterol/Chol-PEG (cholesterol-polyethylene glycol)] showed the highest rate of transfection at N/P 3. Finally, transfection of Cas9/sgRNA by this formulation at N/P 3 resulted in 39% gene-editing efficiency to knockout GFP reporter. The results also show that this CL with no cytotoxicity effect can totally protect the plasmids from enzymatic degradation in serum. The novel PEGylated cholesterol domain lipoplex providing serum stability, higher transfection efficiency and endosomal release can be used for in vivo Cas9/sgRNA delivery and other future gene-therapy applications.

A chemiresistive sensor is described for the lung cancer biomarker hexanal. A composite consisting of molecularly imprinted polymer nanoparticles and multiwalled carbon nanotubes was used in the sensor that is typically operated at a voltage of 4 V and is capable of selectively sensing gaseous hexanal at room temperature. It works in the 10 to 200 ppm concentration range and has a 10 ppm detection limit (at S/ N  = 3). The sensor signal recovers to a value close to its starting value without the need for heating even after exposure to relatively high levels of hexanal. Graphical abstract Schematic presentation of a chemiresistive sensor for detection of hexanal, a cancer biomarker. The hexanal-imprinted polymeric nanoparticles were synthesized, mixed with multiwalled carbon nanotubes and coated on the surface of an interdigitated electrode to produce a nanocomposite chemiresistor gas sensor for hexanal.

A bioluminescence-based assay for ATP can measure cell viability. Higher ATP concentration indicates a higher number of living cells. Thus, it is necessary to design an ATP sensor that is low-cost and easy to use. Gold nanoparticles provide excellent biocompatibility for enzyme immobilization. We investigated the effect of luciferase proximity with citrate-coated gold, silver, and gold–silver core–shell nanoparticles, gold nanorods, and BSA–Au nanoclusters. The effect of metal nanoparticles on the activity of luciferases was recorded by the luminescence assay, which was 3–5 times higher than free enzyme. The results showed that the signal stability in presence of nanoparticles improved and was reliable up to 6 h for analytes measurements. It has been suggested that energy is mutually transferred from luciferase bioluminescence spectra to metal nanoparticle surface plasmons. In addition, we herein report the 27-base DNA aptamer for adenosine-5′-triphosphate (ATP) as a suitable probe for the ATP biosensor based on firefly luciferase activity and AuNPs. Due to ATP application in the firefly luciferase reaction, the increase in luciferase activity and improved detection limits may indicate more stability or accessibility of ATP in the presence of nanoparticles. The bioluminescence intensity increased with the ATP concentration up to 600 µM with a detection limit of 5 µM for ATP.

Background Assessing quality of life (QOL) in elderly needs specific instruments. The Older People’s Quality of Life Questionnaire (OPQOL-35) is one of the common tools that used for measuring quality of life in elderly populations. The questionnaires contains 35 items tapping into eight domains including life overall, health, social relationships and participation, independence, control over life and freedom, home and neighborhood, psychological and emotional well-being, financial circumstances, culture and religion. This study aimed to translate and validate the OPQOL-35 in Iran. Methods Forward-backward procedure was applied to translate the original questionnaire from English into Persian. Then following qualitative face and content validity, a sample of elderly people completed the questionnaire. In order to evaluate the construct validity, exploratory and confirmatory factor analyses was performed. Subsequently, convergent and divergent validity of the factors were evaluated. Reliability was evaluated by performing internal consistency analysis and Intraclass Correlation Coefficients (ICC). Results In all 500 older people completed the questionnaire. The mean age of participant was 68.92 (SD = 6.97) years, and mostly were males (66.6%). The result of exploratory factor analysis showed 8 factors with Eigen values of greater than one, which explained 67.4% of the variance observed. Confirmatory factor analysis showed acceptable fit indexes for the data [Comparative Fit Index (CFI) = 0.92, Minimum Discrepancy Function by Degrees of Freedom divided (CMIN/DF) = 2.832, Root Mean Square Error of Approximation (RMSEA) = 0.067]. The convergent and divergent validity did not support three latent factors (Life overall, Independence, control over life, freedom and Psychological and emotional well-being). Convergent and divergent validity shown that construct fulfilled for the health, social relationships and participation, home and neighborhood, financial circumstances, culture and religion latent factors, however the results did not support the convergent and divergent validity for three latent factors (Life overall, Independence, control over life, freedom and Psychological and emotional well-being). Cronbach’s alpha coefficient for the subscales ranged from 0.65–0.95. Test-retest reliability (ICC) of the questionnaire with two weeks interval were ranged from 0.88–0.95 indicating a good range of reliability. Conclusion The findings suggest that the Iranian version of OPQOL-35 is a valid measure for assessing quality of life in elderly populations in different settings.

Background Gold nanoparticles (GNPs) have been used to sensitize cancer cells and enhance the absorbed dose delivered to such cells. Active targeting can provide specific effect and higher uptake of the GNPs in the tumor cells, while having small effect on healthy cells. The aim of this study was to assess the possible radiosensitiazation effect of GNPs conjugated with AS1411 aptamer (AS1411/GNPs) on cancer cells treated with 4 MeV electron beams. Materials and methods Cytotoxicity studies of the GNPs and AS1411/GNPs were carried out with MTT and MTS assay in different cancer cell lines of MCF-7, MDA-MB-231 and mammospheres of MCF-7 cells. Atomic absorption spectroscopy confirmed the cellular uptake of the gold particles. Radiosensitizing effect of the GNPs and AS1411/GNPs on the cancer cells was assessed by clonogenic assay. Result AS1411 aptamer increased the Au uptake in MCF-7 and MDA-MB-231 cells. Clonogenic survival data revealed that AS1411/GNPs at 12.5 mg/L could result in radiosensitization of the breast cancer cells and lead to a sensitizer enhancement ratio of 1.35 and 1.66 and 1.91 for MCf-7, MDA-MB-231 and mammosphere cells. Conclusion Gold nanoparticles delivery to the cancer cells was enhanced by AS1411 aptamer and led to enhanced radiation induced cancer cells death. The combination of our clonogenic assay and Au cell uptake results suggested that AS1411 aptamer has enhanced the radiation-induced cell death by increasing Au uptake. This enhanced sensitization contributed to cancer stem cell-like cells to 4 MeV electron beams. This is particularly important for future preclinical testing to open a new insight for the treatment of cancers.

The apoptotic protease-activating factor 1 (Apaf-1) split luciferase biosensor has been used as a biological tool for the detection of early stage of apoptosis. The effect of doxorubicin in a cell-based assay and the addition of cytochrome c and ATP in a cell-free system have been used to test the functionality of the reporter for the detection of apoptosome formation. Here, our data established a drug- and cytochrome c/ATP-independent way of apoptosis induction relying on the expression of the biosensor itself to induce formation of apoptosome. Overexpression of Apaf-1 constructs led to increased split luciferase activity and caspase-3 activity in the absence of any drug treatment. Caspase-3 activity was significantly inhibited when caspase-9DN was co-overexpressed, while the activity of the Apaf1 biosensor was significantly increased. Our results show that the Apaf-1 biosensor does not detect etoposide-induced apoptosis.

A bimetallic nanostructure of Co/Cu for the non-enzymatic determination of glucose is presented. The heterostructure includes cobalt thin film on a porous array of Cu nanocolumns. Glancing angle deposition (GLAD) method was used to grow Cu nanocolumns directly on a fluorine-doped tin oxide (FTO) substrate. Then a thin film of cobalt was electrodeposited on the Cu nanostructures. Various characterization studies were performed in order to define the optimum nanostructure for the determination of glucose. The results showed remarkable boosting of the electrocatalytic activity of Co/Cu bimetallic structure compare to the responses achieved by the monometallic structures of Co or Cu. The sensor showed two linear response ranges for the determination of glucose at 0.55 V in 0.1 M NaOH, from 5 μM–1 mM and 2–9 mM. The sensitivity was 1741 (μA mM −1  cm −2 ) and 626 (μA mM −1  cm −2 ), respectively, while the detection limit for a signal-to-noise ratio of 3 was found to be 0.4 μM. The sensor exhibited excellent selectivity and was successfully applied to the determination of glucose in real human blood serum samples. Graphical Abstract Schematic representation of fabrication process of the glucose sensor of Co (Cobalt)/Cu (Copper) on Fluorine doped Tin Oxide (FTO). The current voltage plots show higher electrooxidation activity of the bimetallic nanostructure of Co/Cu/FTO relative to the bare Co/FTO.

Gold nanorods (GNRs) have been nominated as a promising candidate for a variety of biological applications; however, the cationic surfactant layer that surrounds a nanostructure places limits on its biological applicability. Herein, CTAB-GNRs were functionalized via a ligand exchange method using a (C(HK)4-mini PEG-RGD)-peptide to target the overexpressed αvβ3 integrin in cancerous cells, increase the biocompatibility, and gain the ability of gene/drug delivery, simultaneously. To confirm an acceptable functionalization, UV–Visible, FTIR, and Raman spectroscopy, zeta potential, and transmission electron microscopy of nanostructures were done. MTT assay was applied to study the cytotoxicity of nanostructures on two cell lines, HeLa and MDA-MB-231, as positive and negative αvβ3 integrin receptors, respectively. The cytotoxic effect of peptide-functionalized GNRs (peptide-f-GNRs) was less than that of CTAB-coated GNRs (CTAB-GNRs) for both cell lines. Uptake of peptide-f-GNRs and CTAB-GNRs was evaluated in two cell lines, using dark-field imaging and atomic absorption spectroscopy. Peptide-f-GNRs showed a proper cell uptake on the HeLa rather than MDA-MB-231 cell line according to the RGD (Arg-Gly-Asp) sequence in the peptide. The ability of peptide-f-GNRs to conjugate to antisense oligonucleotides (ASO) was also confirmed using zeta potential, which was due to the repeated HK (His-Lys) sequence inside the peptide. The result of these tests highlights the functionalization method as a convenient and cost-effective strategy for promising applications of targeted GNRs in the biological gene/drug delivery systems, and the repeated histidine-lysine pattern could be a useful carrier for negatively charged drug/gene delivery, too. Graphical Abstract

Plasmonic nanoclusters (NCs) have been introduced as new fluorescent materials that have low toxicity and do not undergo photo‐bleaching. Several factors including size and type of the NCs, surface chemistry and even solvent affect their luminescence. Despite extensive studies on tuning the fluorescence properties of NCs by manipulation of the above‐mentioned factors, very few researches have been focused on metal enhanced fluorescence (MEF) of them. In this study, the fabrication of silver dendritic nanostructured surfaces (DNSs) with numerous hotspots and unique plasmonic properties were optimized and DNSs were used as the substrates for fluorescence enhancement of NCs. NCs made of gold, silver and copper were synthesized by different stabilizing agents and compared with each other in terms of their MEF characteristics. The results showed that the stabilizing agent, the synthesis method and type of NCs affected their fluorescence enhancement by the DNSs. Copper NCs stabilized by bovine serum albumin (BSA) had the highest rate of fluorescence enhancement, with enhancement factor of 4.8 ± 0.8. Gold NCs synthesized by glutathione (GSH) and bovine serum albumin (BSA) demonstrated 3.9 ± 0.6 and 3.1 ± 0.4 fold fluorescence enhancement, respectively. The possibility of fluorescence enhancement of NCs in the vicinity of plasmonic nano‐structures introduces attractive platforms for sensing purposes.