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Cancer is a broad term for a class of prevalent diseases as one in three people develop cancer during their lifetime. Although, there are few success stories of cancer therapy, most of the existing medications do not lead to complete recovery. Because of the complexity of cancer, usually a single therapeutic approach is insufficient for the suppression of cancer growth and metastasis. Simultaneous loading and co-delivery of different agents with different physiochemical characteristics to the same tumors have been suggested for minimizing the dose of anticancer drugs and achieving the synergistic therapeutic impacts in cancers treatment. Intense work to develop nanotechnology-based systems as a suitable option for cancer treatment is currently underway. The purpose of this review is to provide an overview of the co-delivery systems based on polymeric nanoparticles including polymeric micelles, dendrimers, poly-d,l-lactide-co-glycolide, polyethylenimine, poly(l-lysine) and chitosan for efficacious cancer therapy.

The authors describe an aptamer-based colorimetric assay for the specific detection of the toxic microcystin leucine-arginine (MC-LR). The method is based on the use of graphene oxide (GO) in a hydrogel matrix, Methylene Blue (MB) acting as an optical probe, streptavidin-modified magnetic particles, and an aptamer (Apt) as a the recognition probe. A complementary strand of the aptamer and adenosine act as promoters in the formation of the GO hydrogel, and the hairpin structure of the aptamer warrants selectivity. In the absence of MC-LR, the gelation of GO sheets is promoted by complementary strand and adenosine, and MB is trapped between GO sheets. Hence, no blue color can be observed in the sample solution. In the presence of MC-LR, GO does not cause the formation of a strong hydrogel structure and a distinct blue color can be observed and measured (at 660 nm) because MB is present in solution. The assay has high selectivity for MC-LR, with a limit of detection (LOD) as low as 219 pM. It was successfully applied to the determination of MC-LR in spiked tap water and serum samples where it gave LODs of 221 and 412 pM, respectively.

Tumor necrosis factor-α (TNF-α) is a cytokine involved in the various physiopathological processes such as autoimmune disorders and inflammation related diseases. Some multidrug resistant (MDR) cancer cell lines including MCF-7/MX are more vulnerable to cytotoxic effects of TNF-α than their parental lines. In this study, breast cancer cell line MCF-7 and its MDR derivative MCF-7/MX were exposed to TNF-α afterward various downstream signaling mediators of TNF-α were analyzed. Although, treatment of MCF-7 cells with TNF-α activated NF-kB and caused RIP1 ubiquitination, TNF-α exposure led to JNK and RIP1 phosphorylation in MCF-7/MX cells. In both cell lines TNF-α did not activate the caspase cascade. Moreover, AnexinV/PI analysis showed that cytotoxic effects of TNF-α on MCF-7/MX is mediated via apoptosis independent mechanisms and inhibition of RIP1 kinase activity using necrostatin-1 revealed that kinase activity of RIP1 plays role in the production of ROS, activation of JNK and cellular death following exposure of MCF-7/MX cells to TNF-α. Overall, it seems that RIP1 ubiquitination and NF-kB activation are prosurvival signaling mediators protecting MCF-7 cells against cytotoxic effects of TNF-α while TNF-α drives MCF-7/MX cells to non-apoptotic cellular death via kinase activity of RIP1, activation of JNK and ROS production.

Recently carbon nanotubes (CNTs) showed promising potentials in different biomedical applications but their safe use in humans and probable toxicities are still challenging. The aim of this study was to determine the acute toxicity of functionalized single walled carbon nanotubes (SWCNTs). In this project, PEGylated and Tween functionalized SWCNTs were prepared. BALB/c mice were randomly divided into nine groups, including PEGylated SWCNTs (75,150μg/mouse) and PEG, Tween80 suspended SWCNTs, Tween 80 and a control group (intact mice). One or 7 days after intravenous injection, the mice were killed and serum and livers were collected. The oxidative stress markers, biochemical and histopathological changes were studied. Subsequently, proteomics approach was used to investigate the alterations of protein expression profiles in the liver. Results showed that there were not any significant differences in malondealdehyde (MDA), glutathione (GSH) levels and biochemical enzymes (ALT and AST) between groups, while the histopathological observations of livers showed some injuries. The results of proteomics analysis revealed indolethylamine N-Methyltransferase (INMT), glycine N-Methyltransferase (GNMT), selenium binding protein (Selenbp), thioredoxin peroxidase (TPx), TNF receptor associated protein 1(Trap1), peroxiredoxin-6 (Prdx6), electron transport flavoprotein (Etf-α), regucalcin (Rgn) and ATP5b proteins were differentially expressed in functionalized SWCNTs groups. Western blot analyses confirmed that the changes in Prdx6 were consistent with 2-DE gel analysis. In summary, acute toxicological study on two functionalized SWCNTs did not show any significant toxicity at selected doses. Proteomics analysis also showed that following exposure to functionalized SWCNTs, the expression of some proteins with antioxidant activity and detoxifying properties were increased in liver tissue.

Detection and quantitation of interferon-gamma (IFN-γ) in blood is of vital importance for diagnosis of latent tuberculosis. The authors describe an electrochemical aptasensor for IFN-γ that is based on a triple-helix molecular switch (THMS). The combination of a THMS with amperometry makes the sensor selective, sensitive and fast (50 min). In the presence of IFN-γ, the structure of the THMS is disassembled and the electrochemical probes, Methylene Blue (MB), can only bind to the signal transduction probe (STP) on the surface of the gold electrode, this leading to a weak peak current. However, in the absence of IFN-γ, the structure of THMS is preserved and MB can interact with the THMS to result in strong current (typically measured at −0.24 V vs. silver reference electrode). Under optimized conditions, the assay has a 3 pg·mL−1 detection limit and a linear range that extends from 10 to 1500 pg·mL−1. Employed to the determination of IFN-γ in spiked serum samples, it gave recoveries that ranged from 91.3% to 102.8%.

Programmed death-ligand 1 (PD-L1) is overexpressed in a variety of cancer cells. Using protein SELEX, aptamers against PD-L1 were identified. After 10 rounds of selection, 2 aptamers (Apt5 and Apt33) were chosen. Due to the higher specificity and affinity of Apt5 for PD-L1, this aptamer was characterized in detail. The ATTO 647 N–labeled aptamer readily internalizes into PD-L1 positive A2780 cells where it can detect human ovarian carcinoma. Hence, fluorometry provides a rapid and sensitive quantitative tool for the detection of these cancer cells with limit of detection (LOD) as low as 10 cells.mL−1 and linear response in the range between 50 and 1000 cells.mL−1. In our perception, the Apt 5 aptamer holds great promise for use in cancer diagnosis and therapy.

Superparamagnetic iron oxide nanoparticles (SPIONs; Fe 3 O 4 ) were synthesized by a “ green ” co-precipitation method in aqueous starch solution as a food media. Powder X-ray diffraction (PXRD) patterns indicated that the synthesized samples were pure Fe 3 O 4 with a spinel structure, and the coating of starch did not undergo any phase change. Fourier transform infrared (FTIR) spectra confirmed the formation of starch coated Fe 3 O 4 nanoparticles. Field emission scanning electron microscopy (FESEM) micrographs illustrated the formation of nanoparticles in the size range of below 25 nm. Magnetic measurements revealed that the saturated magnetization of the starch-SPIONs reached 36.5 emu/g. The non-toxic effect of SPIONs concentration below 50 and 100 μg/ml was observed in the studies of in vitro cytotoxicity on normal and cancerous cell lines, respectively. The dose dependent toxicity made it a suitable candidate for various medical applications.

Leukemia is a cancer of blood cells and bone marrow, leading to death in many patients mainly in children. Over the last several years, aptamers generated by SELEX (Systematic evolution of ligands by exponential enrichment) method, have quickly become a new class of targeting ligands for drug delivery applications and recently have been widely exploited in different biomedical applications, due to several potent properties such as high binding affinity and selectivity, low or no immunogenicity and toxicity, low cost and thermal stability. In this review, we presented in details about aptamers involved in targeting, and treatment of leukemia. Moreover, some analytical approaches such as electrochemical and optical aptasensors were introduced for detection and diagnosis of leukemia. Finally, we discussed about the directions and challenges of aptamer application in this field.

There is a prompt need for determination of aflatoxin B1 (AFB1) in food products to avoid distribution and consumption of contaminated food products. In this study, an accurate electrochemical sensing strategy was presented for detection of AFB1 based on aptamer (Apt)-complementary strands of aptamer (CSs) complex which forms a π-shape structure on the surface of electrode and exonuclease I (Exo I). The presence of π-shape structure as a double-layer physical barrier allowed detection of AFB1 with high sensitivity. In the absence of AFB1, the π-shape structure remained intact, so only a weak peak current was recorded. Upon the addition of AFB1, the π-shape structure was disassembled and a strong current was recorded following the addition of Exo I. Under optimal conditions, the electrochemical signals enhanced as AFB1 concentrations increased with a dynamic range of 7-500pg/mL and a limit of detection (LOD) of 2pg/mL. The developed aptasensor was also used to analyze AFB1 spiked human serum and grape juice samples and the recoveries were 95.4-108.1%.

Mucin 1 (MUC1) is a protein usually found on the apical surface of most normal secretory epithelial cells. However, in most adenocarcinomas, MUC1 is overexpressed, so that it not only appears over the entire cell surface, but is also shed as MUC1 fragments into the blood stream. These phenomena pinpoint MUC1 as a potential target for the diagnosis and treatment of cancer; consequently, interest has increased in MUC1 as a molecular target for overcoming cancer therapy challenges. MUC1 currently ranks second among 75 antigen candidates for cancer vaccines, and different antibodies or aptamers against MUC1 protein are proving useful for tracing cancer cells in the emerging field of targeted delivery. The unique properties of MUC1 aptamers as novel targeting agents, and the revolutionary role that MUC1 now plays in cancer therapy, are the focus of this review. Recent advancements in MUC1-targeted cancer therapy are also assessed.

According to the serious threat of lead to the public health, plenty of methods have been developed for monitoring of this element, but most of these methods suffer from limitations such as requirement to long time, costly instruments and complicated procedures. Recently, functional nucleic acid molecules are highly regarded for the determination of heavy metal ions. Two classes of these molecules have been applied to design lead biosensors: lead specific DNAzymes, DNA molecules with catalytic activity and high specificity for lead, and lead induced allosteric G-quadruplex oligonucleotides. In this review, recent advances in nucleic acid based biosensors for lead have been discussed in two main optical and electrochemical groups.

The common cancer treatment strategies like chemotherapy and radiotherapy are nonspecific and can trigger severe side effects by damaging normal cells. So, targeted cancer therapies, such as apoptosis induction, have attracted great attention in recent years. In this project, two nano-complexes, MUC1 aptamer-NAS-24 aptamer-Graphene oxide (GO) and MUC1 aptamer-Cytochrome C aptamer-GO, were designed to induce cell programmed death in MDA-MB-231 and MCF-7 cells (breast cancer cell lines) and to verify the level of apoptosis in both cell lines. MUC1 aptamer was a molecular recognition probe that led the internalization of two nano-complexes into MDA-MB-231 and MCF-7 cells (MUC1 positive cells) but not into HepG2 cell (liver cancer cell line, MUC1 negative cells). The apoptosis induction relied on binding of NAS-24 aptamer to its target, vimentin, in MDA-MB-231 and MCF-7 (target cells) with different levels of vimentin content. The function of first nano-complex was confirmed by binding of FAM-labeled cytochrome C aptamer to its target (cytochrome C) which was released from mitochondria, based on the function of the first nano-complex. Fluorometric analysis and gel retardation assay proved the formation of nano-complexes. The results of flow cytometry and fluorescence microscopy indicated efficient apoptosis induction just in target cells (MDA-MB-231 and MCF-7 cells) but not in non-target cells (HepG2 cell). The results of MTT assay also confirmed cell death process. Overall, our results proved excellent targeted apoptosis in breast cancer cells by designed nano-complexes which can be applied as an efficient cancer therapy method.

The authors describe an electrochemical aptasensing platform for the determination of Pb(II) ions. The assay is based on the use of gold nanoparticles (AuNPs) (that facilitate electron transfer), the enzyme exonuclease III (Exo III; assisting signal amplification), and a hairpin structured complementary strand of an aptamer that prevents binding of AuNPs to the surface of the sensor electrode in the presence of Pb(II). In the absence of Pb(II), AuNPs attach to the surface of the gold electrode, and this leads to a strong voltammetric signal. In the presence of Pb(II), however, the AuNPs do not bind to the surface of the electrode because of the hairpin structure of the complementary strand. As a result, the peak current (typically measured at 0.17 V vs. silver reference electrode) remains weak. The method has a 149 pM detection limit. It was applied to the analysis of spiked tap water and human serum samples and gave recoveries between 92 and 105.25%.

Non-viral vectors are of interest as therapeutic gene delivery agents in gene therapy, because they are simple to prepare, easy to modify and have definable safety profiles compared to viral vectors. The potential of gene therapy in the treatment of renal diseases is limited by a lack of effective kidney-targeted gene delivery systems. Aminoglycoside antibiotics gentamicin and neomycin were connected by amide linkages to carboxyl groups on carboxyalkylated-PEI25 (25kDa PEI) or carboxyalkylated-PEI10 (10kDa PEI). Aminoglycoside-carboxyalkylated-PEI conjugates were characterized with respect to size, surface charge density, DNA condensation ability, and buffering capacity. Polyplexes prepared by electrostatic interaction between aminoglycoside-carboxyalkylated-PEIs and enhanced green fluorescent protein-expressing (EGFP) plasmid DNA had appropriate nano-scale size (143-173nm). Their targeting potential was investigated in cultured HK-2 immortalized human cortex/proximal tubule kidney epithelial cells, which expresses megalin, a scavenger receptor that mediates endocytosis of a diverse group of ligands, including aminoglycoside antibiotics. Aminoglycoside-carboxyalkylated-PEIs significantly increased EGFP gene transfection efficiency in HK-2 cells by ∼13-fold for aminoglycoside-carboxyalkylated-PEI25 and ∼7-fold increase for aminoglycoside-carboxyalkylated-PEI10 relative to the corresponding PEIs without aminoglycosides. The transfection efficiency of polyplexes was dependent on the weight ratio of aminoglycoside-containing ligand in the carrier. In the presence of a range of concentrations of human serum albumin, which competes for megalin binding, aminoglycoside-carboxyalkylated-PEI-mediated transfection was reduced to background levels. These results suggest that aminoglycoside-carboxyalkylated-PEI polyplexes can target megalin-expressing kidney-derived cells in vitro resulting in improved transfection efficiency with low cytotoxicity.

The authors describe a colorimetric assay for the detection of fluoroquinolones (FQs). It is based on the use of gold nanoparticles (AuNPs) modified with complementary DNA strands and analyte-specific FQ-binding aptamers. The modified AuNPs possess enzyme-like activity that can catalyze the reduction of nitrophenol by NaBH4. In the absence of ciprofloxacin, the flower-shape coating on the AuNPs prevents the reduction of yellow 4-nitrophenol. In the presence of ciprofloxacin, the DNA/aptamer flower leaves on the AuNPs and the AuNPs can exert their catalytic activity. This results in a color change from yellow to colorless. The assay is highly selective for FQs, fast (1 h), and has a limit of detection as low as 1.2 nM in case of ciprofloxacin. It was successfully applied to the determination of ciprofloxacin in spiked water, serum and milk samples to give LODs of 1.3, 2.6 and 3.2 nM, respectively.

Staphylococcus aureus ( S. aureus ) is most common causes of hospital-acquired infections and food-associated disease, also staphylococcal food poisoning (SFP) are known as the one of the most important foodborne illnesses worldwide. Many different methods have been developed for the detection and quantification of S. aureus and Staphylococcus aureus enterotoxins (SEs). But most of these methods are usually time-consuming and need complicated sample preparation steps. Therefore, it is of great interest to develop a rapid, simple, and sensitive detection method. In the last years, aptamers, are used as a new biosensor platform for detection of S. aureus in different samples. In this review, recent advances and applications of optical and electrochemical aptamer-based biosensors for the detection and quantitative of S. aureus and enterotoxins in details have been discussed.

Determination of fluoroquinolones (FQs) in foodstuffs and environment is of great importance. In this study, a novel electrochemical sensing method was developed for rapid, highly sensitive and specific detection of FQs, based on aptamer (Apt) as molecular recognition probe, single-stranded DNA-binding protein (SSB) as a physical and negatively charged barrier for the access of redox probe ([Fe(CN)6]3−/4−) to the surface of gold electrode. The designed electrochemical aptasensor needs less than 1 h for detection of ciprofloxacin. In the absence of ciprofloxacin, SSB interacts with Apt and restricts the access of redox probe to the surface of electrode, leading to a weak current signal. In the presence of target, SSB could not bind to the Apt, resulting in more access of redox probe to the surface of electrode and a strong current signal. The designed electrochemical sensor exhibited high specificity toward FQs with a limit of detection (LOD) as low as 263 pM for ciprofloxacin. Moreover, the developed sensing method was successfully applied for determination of ciprofloxacin in serum, milk and water samples with LODs of 336, 351 and 261 pM, respectively.

In recent years, superparamagnetic iron oxide nanoparticles have attracted a great attention due to their various biomedical applications, such as magnetic resonance imaging, targeted drug delivery, and hyperthermia. In this article, γ-Fe2O3 magnetic nanoparticles (Maghemite) were prepared in oleic acid media by co-precipitation method. The oleic acid, a monounsaturated fatty acid was used as the capping and stabilizing agent during the synthesis of the magnetic nanoparticles. Characterization of obtained nanoparticles were performed using powder X-ray diffraction (PXRD), field emission scanning electron microscopy (FESEM), Fourier transform infrared spectra (FTIR), and vibrating sample magnetometer (VSM). The crystallite size of γ-Fe2O3 nanoparticles was achieved in the range between 16.2 and 26.8 nm. The FESEM demonstrated the regular spheres of γ-Fe2O3 nanoparticles. The obtained nanoparticles were coated with oleic acid indicating by FTIR analysis. The resulted oleic acid-coated nanoparticles were shown superparamagnetic properties (~52 emu/g). This suggested method is simple and rapid to fabricate superparamagnetic nanoparticles which make them appropriate candidates for theranostic application in future studies.

The authors describe an amperometric aptasensor for the mycotoxin ochrotoxin A (OTA). It is based on the use of a modified gold electrode containing aptamer (Apt) as the sensing ligand, Methylene Blue (MB) as the redox indicator, single-walled carbon nanotubes (SWCNTs) as electrochemical signal amplifiers, and complementary strands of aptamer (CSs) as assisting DNA. In the absence of OTA, the duplex formed between Apt and CSs on the electrode remains intact. Thus, a strong electrochemical signal is observed due to the presence of the redox marker MB in the duplex. If OTA is added, the duplex will be disassembled and MB and SWCNTs will be released from the surface of the gold electrode. Hence, the electrochemical signal is weakened. The method is highly specificity for OTA and has a limit of detection as low as 52 pM. The aptasensor was successfully applied to the determination of OTA in (spiked) serum and grape juice samples where it shows LODs of 134 and 58 pM, respectively.

In recent years, magnetic nanoparticles are increasingly studied and exploited for their potential applications as magnetic resonance imaging (MRI 1 ) contrast agents, cancer treatment, targeted therapy, delivery vectors and hyperthermia. Todays, magnetic systems based on polymeric materials such as poly(lactic-co-glycolic acid) (PLGA 2 ) have been of special interest for their biomedical applications. In this study, we achieved an effective method for encapsulation of sized-controlled oleic acid-coated superparamagnetic iron oxide (SPIO 3 NPs 4 ) into the PLGA nanospheres via a modified multiple emulsion solvent evaporation method (O1/W1/O2/W2 5 ) resulted in development of the NPs with narrow size distribution and acceptable magnetic properties that are very vital and curtail at targeting and magnetic properties of NPs for both anti-cancer therapy and magnetic resonance imaging studies. The SPIO NPs and SPIO-PLGA nanospheres showed spherical morphology with narrow size distribution of 10 nm and 130 nm, respectively. SPIO-PLGA nanospheres with high SPIO loading of 18.0% and magnetic properties of 5.9 emu/g were obtained. Furthermore, SPIO-PLGA NPs enhance the contrast of relaxation time (T1 6 )-weighted imaging in tumor site. The prepared SPIO NPs and magnetic PLGA nanosphere could be promising superparamagnetic nanoparticles for simultaneous diagnostic and therapeutic applications.

Targeted nano-carriers are highly needed to promote nucleic acid delivery into the specific cell for therapeutic approaches. Pullulan as a linear carbohydrate has an intrinsic liver targeting property interacting with asialoglycoprotein receptor (ASGPR) found on liver cells. In the present study, we developed polyamidoamine (PAMAM)-pullulan conjugates and investigated their targeting activity in delivering gene into liver cells. The particle size, zeta potential, buffering capacity and ethidium bromide exclusion assays of the conjugates were evaluated. The cytotoxicity and transfection efficiency of new derivatives were assessed following in vitro transfection of HepG2 (receptor positive) and N2A (receptor negative) cell lines. Size of conjugated polymers ranged between 118 and 184 nanometers and their cytotoxicity were similar to PAMAM. Among six produced nanocarriers, G4PU4 and G5PU4 enhanced transfection efficiency in HepG2 cells compared to unmodified PAMAM. Therefore, the PAMAM-pullulan derivatives seem to improve delivery of nucleic acids into the liver cells expressing asialoglycoprotein receptor with minimal transfection in non-targeted cells.

A new series of quinoline analogues was designed and synthesized as Hsp90 inhibitors. The cytotoxic activity of the synthesized compounds was evaluated against three human cancer cell lines including MCF-7 (human breast cancer cells), DU145 (human prostate cancer cell lines), and A549 (adenocarcinomic human alveolar basal epithelial cells). Some of our compounds (13a-13f) showed significant cytotoxic activity on MCF-7 cells. The most potent anti-proliferative compounds were also tested against Her2, a client protein of Hsp90. Compound 13d that demonstrated the highest antiproliferative activity in the series, was found the most potent one for both Her2 protein degradation and Hsp70 protein induction as well. Molecular modeling studies displayed possible mode of interaction between this compound and N-terminal ATP-binding site of Hsp90.

Context: Polyethylenimine (PEI) is a cationic polymer commonly used in gene transfer. Although numerous investigations have indicated that PEI can induce apoptosis/necrosis but the mechanism of its cytotoxicity is still poorly understood. Objective: The purpose of this study was to investigate the effects of PEI/DNA complexes on the expression of apoptotic genes in human colon adenocarcinoma cells (HT29). Methods: HT29 cells were exposed to PEI/DNA complex (C/P = 0.8) for 24 h. Then, qRT PCR was used to assess the expression of 26 apoptotic-related genes. Result: Analysis of the transcript level of genes revealed that while the expression of anti-apoptotic genes such as Bclx, Bcl2, NFkB, and AIF was not significantly reduced but the expression of pro-apoptotic genes such as Fasl, Bax, TNFR1, DR4, Casp8, and cytochrome C was considerably increased in transfected HT29 cell lines. Conclusions: Our results showed that PEI could increase the level of pro-apoptotic genes and decrease antiapoptotic genes...

The clinical administration of epirubicin (Epi) in the treatment of cancer has been restricted, owing to its cardiotoxicity. Targeted delivery of anticancer agents could increase their therapeutic efficacy and decrease their off-target effects. In this study, a novel Epi-DNA diamond nanostructure (DDN) conjugate containing two kinds of aptamers (MUC1 and ATP aptamers) was designed and evaluated in the treatment of target cells, including C26 cells (murine colon carcinoma cell) and MCF-7 cells (breast cancer cell). DDN and Epi-DDN conjugate formations were analyzed by gel retardation assay and fluorometric analysis, respectively. Release profiles of Epi from the developed Epi-DDN conjugate were evaluated at pHs 5.4 and 7.4. For the MTT assay (cell viability study), CHO cells (Chinese hamster ovary cell, nontarget), C26 and MCF-7 cells (target) were treated with the Epi-DDN conjugate, DDN, Epi, Epi-DDN conjugate without ATP aptamer and Epi-DDN conjugate without MUC1 aptamer. Internalization of the Epi-DDN conjugate was assessed by flow cytometry analysis and fluorescence imaging. Finally, the designed Epi-DDN conjugate was utilized for inhibition of tumor growth in vivo. 10 μM Epi was efficiently loaded in 1 μM DDN. The drug was released from the Epi-DDN conjugate in a pH-sensitive manner (higher release in acidic conditions). The results of flow cytometry analysis and fluorescence imaging confirmed that the developed Epi-DDN conjugate was effectively internalized into target cells, but not into nontarget cells. The results of the MTT assay were consistent with the internalization data. The Epi-DDN conjugate had more cytotoxicity in MCF-7 and C26 cells and less cytotoxicity in CHO cells in comparison with Epi alone. Moreover, the Epi-DDN conjugate could effectively prohibit tumor growth in vivo.

We reported SN38-loaded polymersomes formulated with amphiphilic block copolymers based on HPMA and either e-caprolactone or lactic acid through employing ring-opening polymerization, carbodiimide chemistry and a reversible addition-fragmentation chain transfer polymerization technique. In this regard, we successfully synthesized five chimeric polymersomes based on different percentage of the synthesized copolymers. The prepared chimeric polymersomes based on PCL-b-PHPMA:PLA-b-PHPMA at ratio of 1:3 exhibited superior loading capacity in comparison with other chimeric polymersomes. In order to increase therapeutic index of the prepared systems, AS1411 aptamer was implemented as targeting ligand. In vivo study revealed that the intravenous single dose injection of targeted chimeric polymersomes to C26 tumor bearing mice had remarkable efficacy in inhibiting tumor growth. It could be concluded that the chimeric polymersomes fabricated from PCL-b-PHPMA and PLA-b-PHPMA at a ratio of 1:3 have great potential for SN38 encapsulation while providing controlled sustained release properties with targeting capability via AS1411 aptamer conjugation.

Cell-based delivery system is a promising strategy to protect therapeutic agents from the immune system and provide targeted delivery. Mesenchymal stem cells (MSCs) have recently been introduced as an encouraging vehicle in cell-based gene therapy due to their unique features including tumor-tropic property and migratory ability. However, gene transfer into MSCs is limited due to low efficiency and cytotoxicity of carriers. In this study, we designed a novel delivery system based on polyethylenimine (PEI25 ) to improve these features of carrier and transfect plasmid encoding TRAIL to MSCs. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a death ligand of TNF family with selective effect on cancerous cells. Then, death induction and migration ability of TRAIL-expressing MSCs was studied in melanoma cells. The effect of engineered-MSCs as an antitumor vehicle was also investigated in mice bearing melanoma cells. Our findings indicated that heterocyclic amine derivative of PEI25 showed significant improvement in MSCs viability determined by MTT assay and gene expression using fluorescent microscopy, flow cytometry, and Western blot analysis. We observed that engineered-MSCs could migrate toward and induce cell death in B16F0 cells in vitro. The single administration of TRAIL-expressing MSCs could delay tumor appearance and efficiently reduce tumor weights. Hematoxylin and eosin staining of tumor sections revealed extensive neoplastic cells necrosis. Furthermore, engineered-MSCs could migrate and localize to tumors sites within 5 days. Our results indicated that MSCs engineered by modified-PEI/TRAIL complexes could be considered as a promising cellular vehicle for targeted tumor suppression.

Accumulation at tumor tissue without any damage to healthy normal tissues is an ultimate goal in cancer therapy. Despite many efforts in the field of cancer therapy, this disease remains as the major reason of mortality all over the world. Gene therapy has introduced great opportunity to fight against cancer disease. It should be noted that still some obstacles limit clinical application of gene delivery approach, which have to be overcome for efficient transportation of therapeutic gene to the site of action. In this regard, carbon nanomaterials and their unique physical and chemical properties such as their capability of DNA protection have attracted much attention in the field of nanomedicine and non-viral carriers for therapeutic genes. Although, negligible solubility of carbon nanomaterials in biological environments has limited their biomedical application but their structural characteristics facilitate their chemical modifications thereby overcoming their solubility problem. Moreover, hybridization of modified carbon materials with different polymers provides more biocompatible and capable systems for gene delivery purposes. In the current review, we summarized hybrid carbon-based materials as non-viral carriers for gene delivery.

In this study, we reported doxorubicin (DOX)-encapsulated nanoparticles (NPs) formulated with biocompatible and biodegradable poly (lactic-co-glycolic acid) (PLGA) and modified with a 13-amino acid peptide (S3) against sodium/potassium (Na

The objective of the current study is to design and delivery of targeted PEG-PCL nanopolymersomes encapsulated with Gadolinium based Quantum Dots (QDs) and Doxorubicin (DOX) as magnetic resonance-florescence imaging and anti-cancer agent. Diagnostic and therapeutic efficiency of the prepared theranostic formulation was evaluated in vitro and in vivo. Hydrophobic QDs based on indium-copper-gadolinium-zinc sulfide were synthesized and characterized extensively. Hydrophobic QDs and hydrophilic DOX were loaded in PEG-PCL polymersomes through double emulsion method. Drug release pattern was studied in both citrate (pH 5.4) and phosphate (pH 7.4) buffer during 10 days. Both fluorescence and magnetic properties of bare QDs and prepared formulations were studied entirely. AS1411 DNA aptamer was covalently attached to the surface of polymersomal formulation in order to prepare targeted drug delivery system. Cellular cytotoxicity and cellular uptake analysis were performed in both nucleolin positive (MCF7 and 4T1) and nucleolin negative (CHO) cell lines. After in vitro evaluations, anti-tumor efficiency and diagnostic capability of the formulation was investigated in 4T1 tumor baring mice. Scanning emission electron microscopy (SEM) confirmed spherical shape and around 100 nm size of prepared formulations. Transmission electron microscopy (HRTEM) showed crystal shape of QDs with size of 2-3 nm. Drug release study obtained controlled release of encapsulated DOX and stability of formulation in physiologic condition. MTT and flow cytometry results demonstrated that AS1411 aptamer could enhance both toxicity and cellular uptake in nucleolin overexpressing cell lines (P 0.05). Moreover, aptamer targeted formulation could increase survival rate and tumor inhibitory growth effect in 4T1 tumor baring mice (P 0.05). Our results verify that aptamer targeted polymersomes loaded with non-toxic QDs as a diagnostic agent and DOX as an anti-cancer drug, could provide a theranostic platform with the purpose of optimization of treatment process and minimization of systemic side effects.

The present study evaluated biochemical endpoints characterizing acrylamide (ACR) neurotoxicity in the cortex of rats, following the possible neuroprotective activity of thymoquinone (TQ), an active constituent of Nigella sativa. ACR (50 mg/kg, intraperitoneal [i.p.]) concurrently with TQ (2.5, 5 and 10 mg/kg, i.p.) for 11 days were administered to rats. As positive control, vitamin E was used. After 11 days of injections, narrow beam test (NBT) was performed. The levels of reduced glutathione (GSH) and malondialdehyde (MDA) were measured and Western blotting was done for mitogen-activated protein kinases (MAPKinases) and apoptosis pathways proteins in the rats’ cortex. Additionally, Evans blue assay was done to evaluate the integrity of blood brain barrier (BBB). Administration of ACR significantly induced gait abnormalities. A significant decrease and increase in the levels of GSH and MDA was observed in the cortex of ACR-treated rats, respectively. The elevation in the levels of caspases 3 and 9, glial fibrillary acidic protein (GFAP) content, and Bax/Bcl-2, P-P38/P38 and P-JNK/JNK ratios accompanied by reduction in myelin basic protein (MBP) content and P-ERK/ERK ratio were noticed in the ACR group. TQ (5 mg/kg) improved gait abnormalities, and restored these changes. ACR affected the integrity of BBB while TQ was able to maintain the integrity of this barrier. TQ reversed the alterations in the protein contents of MAP kinase and apoptosis signaling pathways as well as MBP and GFAP contents, induced by ACR. It protected against ACR-mediated neurotoxicity, partly through its antioxidant and antiapoptotic properties.

In the current research, the synthesis of polysaccharide-based polymersomes for targeted delivery of doxorubicin is reported. To this aim, doxorubicin was encapsulated in aqueous compartment of hyaluronan-polycaprolactone polymersomes via nanoprecipitation method. Then the therapeutic index of the prepared formulation was studied in metastatic breast cancer model in vitro and in vivo. The size of obtained polymersomes was 146.2 ± 9.6 nm and offered the efficiency of encapsulation and the content of loading %54.9 ± 4.0 and %3.6 ± 0.4, respectively. The obtained results exhibited that the HA-PCL polymersomes controlled the release of DOX in a sustained manner. Then, the CD44-receptor mediated endocytosis through hyaluronan shell of the prepared formulation was confirmed in murine 4T1 and human MCF-7 cancer cell lines implementing flow cytometry and MTT assays. Much better in vivo antitumor efficacy and wider tumor tissue necrosis and better bio-distribution features of this formulation in comparison with PEG-PCL-DOX nanoparticles suggested that HA-PCL-DOX can potentially reduce off-target effects due to its targeting capability.

Dual-modal imaging probes based on fluorescence (FL) and magnetic resonance (MR) modalities have attracted great attention due to their ability to combine the target specificity and high penetration into body tissues. In this study, we developed a potent nanocarrier with an effective photoluminescent emission and MR imaging capacity to deliver the doxorubicin to breast cancer 4T1 cells. The nanocarrier was fabricated by coating of quantum dots (QDs) with mesoporous silica followed by amine functionalization of the silica surface. Then, the doxorubicin was loaded into the silica pores and biheterofunctional PEG was covalently bound to the surface of core–shell quantum dot mesoporous silica nanoparticles. In order to target the DOX-loaded nanoparticles, the EpCAM DNA aptamer was attached on the surface of the DOX-loaded PEGylated nanoparticles. The synthesized NPs were analyzed for their size distribution, morphology, zeta potential and magnetic susceptibility using HRTEM, SEM and VSM analysis. The QD-encapsulated mesoporous silica revealed spherical shapes with an average particle size of 100 nm. The maximum encapsulation efficacy of doxorubicin in the silica pores was 25%. The in vitro release assessment demonstrated the pH-sensitive release of doxorubicin from the designed formulations. The in vitro cytotoxicity assays indicated that the aptamer targeted nanoparticles showed greater cytotoxicity than both non-targeted NPs and free DOX toward 4T1 and MCF-7 cell lines. The in vivo studies in 4T1 tumor-bearing Balb/c mice demonstrated that EpCAM aptamer could specifically deliver the DOX-loaded nanoparticles into the tumor tissue and cause remarkable inhibition of tumor growth as compared to non-targeted formulation and free DOX. Moreover, the in vivo MR and fluorescent imaging in 4T1 tumor-bearing mice confirmed the accumulation and residence of targeted system in tumor tissue even 24 h post-injection. This work presents a novel system for preparing bimodal imaging theranostic NPs through hybridization of silica and magnetic-fluorescent quantum dots.

Recent technological approaches in drug delivery have attracted scientist interest for improving therapeutic index of medicines and drug compliance. One of the powerful strategies to control the transportation of drugs is implementation of intelligent stimuli-responsive drug delivery system (DDS). In this regard, tumor tissues with unique characteristics including leaky vasculature and diverse enzyme expression profiles facilitate the development of efficient enzyme-responsive nanoscale delivery systems. Based on the stimuli nature (physical, chemical and biological), these systems can be categorized into three groups according to the nature of trigger initiating the drug release. Enzymes are substantial constituents of the biotechnology toolbox offering promising capabilities and ideal characteristics to accelerate chemical reactions. Nanoparticles which have the ability to trigger their cargo release in the presence of specific enzymes are fabricated implementing fascinating physico-chemical properties of different materials in a nanoscale dimension. In order to reduce the adverse effects of the therapeutic agents, nanocarriers can be utilized and modified with enzyme-labile linkages to provide on-demand enzyme-responsive drug release. In the current review, we give an overview of drug delivery systems which can deliver drugs to the tumor microenvironment and initiate the drug release in response to specific enzymes highly expressed in particular tumor tissues. This strategy offers a versatile platform for intelligent drug release at the site of action.

Quinones such as 1,4-naphthoquinones are abundant in nature and naphthoquinone based natural products are known to possess anticancer activity. This pharmacophore is known to convey anticancer activity to some drugs such as streptonigrin, mitomycin A, etc. We synthesized and characterized different classes of naphthoquinone derivatives including bis naphthoquinone, 2-arylaminonaphthoquinone, benzoxantene-6,11-dione and benzoacridine-5,6-dione derivatives instead of the expected 2-hydroxy-3-(substituted phenyl(aryl amino)methyl)naphthalene-1,4-dione derivatives from the reaction of 2-hydroxy1,4-naphthoquinone (lawson) with different benzaldehydes and aryl amines. Benzoacridine-5,6-dione derivatives and related imines showed potent anti-breast cancer activity in MCF-7 cancer cells. The in-vitro results revealed that five compounds benzoacridinedione derivatives (6b and 7b) and imines (13, 14 and 15) by the IC50 range of 5.4-47.99 μM are the most potent anti-breast cancer structures.

Tacrolimus (TAC) is an immunosuppressant for preventing solid-organ transplant rejection. Because of its narrow therapeutic window, analytical methods which can detect TAC in serum samples with high accuracy and reliability are required. In this study, specific aptamers (Apt122 and Apt125) for TAC were isolated via systematic evolution of ligands by exponential enrichment method using magnetic beads to immobilize the target. After determination of binding constants of aptamers by flow cytometry analysis, Apt122 was selected and labeled with ATTO 647 N as a fluorophore to develop a fluorescent sensing platform for detection of TAC using graphene oxide (GO) as a fluorescence quencher. The designed aptasensor could detect TAC in phosphate buffer saline (10 mM PBS) and serum samples with detection limits as low as 1.4 and 2.5 nM, respectively.

Chemotherapy is the most widely used treatment for cancer therapy, but its efficacy is limited by the side effects of non-specific cytotoxic drugs. Ligand-based targeting drug-delivery system is a solution to circumvent this issue. In this study, an ABCG2 aptamer-doxorubicin complex was prepared, and its efficacy in targeted drug delivery tomitoxantrone-resistance breast cancer cell line (MCF7/MX) was evaluated. The formation of aptamer-doxorubicin physical complex was analyzed by fluorometric analysis. The cytotoxicities of doxorubicin and aptamer-doxorubicin complex on MCF7 and MCF7/MX cell lines were evaluated by the MTT assay, and IC50 values were obtained. Cellular uptake of aptamer-doxorubicin complex was assessed by flow cytometry cellular uptake assay. Results: Fluorometric analysis of aptamer-doxorubicin showed 1-1.5 molar ratio of the drug to the aptamer could efficiently quenchDox fluorescence.MTTassay results showed that MCF7/MXcells were more resistant to doxorubicin than MCF7 cells (IC50 : 3.172 +/- 0.536 and 1.456 +/- 0.154 μM, respectively). Flow cytometry andMTTassay results showed that the aptamer-doxorubicin complex could increase the uptake and cytotoxicity of doxorubicin inMCF7/MX cell line in comparisonwith free doxorubicin, while the same treatments had no effect on IC50 of Dox on MCF7 cells. The results proposed that the ABCG2 aptamer-drug complex can be effectively used for specific drug delivery to ABCG2-overexpressing cells.

In this study, a sensor is described for determination of patulin by using ratiometric fluorescence measurement and strand displacement strategy. In the presence of patulin, the ratiometric fluorescence response decreases, owing to disassembly of DNA duplex structure and target-mediated release of TAMRA-labeled complementary DNA sequence2 (cDNA2). While, in the absence of target, the fluorescence resonance energy transfer (FRET) phenomenon happens between FAM and TAMRA under excitation at 490 nm, resulting in the enhancement of ratiometric signal. The use of ratiometric fluorescence signal with different signal indicators avoids the problem of environmental interference and improves the sensitivity of the aptasensor. Also, the DNA duplex structure contains minimum aptamer-involved base pair sequence, resulting in further improvement of the aptasensor sensitivity. This sensing platform provided a wide linear range from 15 ng/L to 35 μg/L and a detection limit of 6 ng/L for patulin. The aptasensor was used to determine patulin in spiked apple juice samples and showed satisfactory results.

AS1411 is a 26-mer G-rich DNA aptamer which has been broadly employed in the field of targeted drug delivery, due to its capability to bind to nucleolin protein on the surface of cancer cells. In this work, it has been shown for the first time that in addition to nucleolin, AS1411 aptamer could bind to copper ions (Cu2+) with high affinity and selectivity, affecting AS1411 usage in drug delivery systems as a targeting agent. In this study, besides the evaluations of the affinity of AS1411 to different ions and the impact of Cu2+ on targeted drug delivery employed AS1411 aptamer as a targeting agent, a simple and ultra-sensitive fluorescent aptasensor was fabricated for Cu2+ detection through applying AS1411, its complementary strand and magnetic beads coated with streptavidin. Gel Red (GR) was also used as a fluorescent dye. The fabricated aptasensor offered the possibility of condensing samples with different volumes. The detection limit of the sensor was 0.01 μM towards Cu2+ in serum samples. The efficacy of this sensor was further confirmed by comparing Cu2+ levels in serums of healthy people with patients suffering from Wilson's disease, Alzheimer's disease and Diabetes Mellitus using the proposed sensing platform.

Graphene hybrid materials have crucial role in the development of novel advanced functional nanomaterials. Research in graphene hybrid functional materials has provided smart materials that integrate the best characteristics of the inorganic 2-D graphene structure with organic or biological realms. The properties of hybrid materials are not only the sum of the individual contributions, and the crucial role of their inner interfaces could be dominant. Graphene hybrid materials are divided into two classes comprising class 1 in which graphene and other components are embedded via hydrogen, van der Waals, or ionic bonds and class 2 where graphene and other components are linked together through covalent or ionocovalent bonds. Both approaches provide the necessary cohesion to hold the graphene and other constituents in the hybrid platform. Hybrid graphene materials do not only represent creative opportunities for the fabrication of unique materials for research but also, due to their improved unique properties, offer promising applications in many areas especially in medicine. This chapter comprehensively reviews the graphene types, graphene hybridization methods, and graphene hybrid applications in biomedical areas.

Herein, a novel linear DNA nanostructure (LDN)-based delivery system was designed and prepared to efficiently co-deliver both epirubicin (Epi), as a chemotherapy drug, and antimiR-10b, as a therapeutic oligonucleotide, into breast cancer cells (MCF-7 and 4T1 cells). Firstly, the LDN, comprised of AS1411 aptamer (targeting agent), FOXM1 Apt (therapeutic aptamer), and complementary strand (linker), was prepared to carry both Epi and antimiR-10b. This targeted system is highly stable in serum and easy to be constructed. The Epi-loaded LDN structure showed a remarkable internalization for target cells (MCF-7 and 4T1 cells, nucleolin positive) in comparison with CHO cells (nucleolin negative, non-target). Furthermore, based on the MTT assay, the Epi-loaded LDN significantly decreased the cell viability of MCF-7 and 4T1 cells, while the non-targeted cells indicated less cytotoxicity for this structure, showing the targeting ability of Epi-loaded LDN. Moreover, the ability of tumor growth inhibition of the Epi-loaded LDN structure was significantly much more than free Epi and LDN in tumor-bearing mice, suggesting the significance of combination therapy for tumor treatment.

Herein a simple fluorescent aptasensor is introduced to quantitatively monitor tobramycin (TOB) antibiotic by using the inherent hairpin structure of TOB aptamer and SYBR Green I (SGI) dye, as the biorecognition element and signal reporter, respectively. In the presence of TOB, the preferential binding of the aptamer towards its target induces the conformational change of the aptamer from hairpin-like to a single string structure. Hence, the SGI intercalation is reduced, decreasing the fluorescent intensity. Under the effect of experimental conditions, there was a wide linear relationship between the relative fluorescence emission and TOB concentration in the range of 0.1–6 µM. Besides, the aptasensor could detect TOB with the detection limit as low as 0.063 µM. The developed aptasensor was utilized to determine TOB in human serum and milk samples with the detection limits of 0.043 and 0.034 µM, respectively. The label-free aptasensor with the main features of feasibility, simplicity and high sensitivity holds the superior potential to develop a low-cost sensing method for human diagnostics, food control, and environmental monitoring. The designed aptasensor can be efficiently applied by non-specialist consumers for on-site monitoring of the diverse targets by substituting their specific aptamers.

Hibernation is an important winter survival strategy for many small mammals. By sinking into a deep torpor where metabolic rate can be as low as 1–5% of the resting rate in euthermia, animals accrue huge energy savings that allow survival, typically without eating, for many months. Hibernating ground squirrels show a net reduction in the total adenylate pool of skeletal muscle during torpor, but the ATP/ADP ratio and adenylate energy charge remain stable. A key enzyme involved in managing adenylate pool size is 5′-adenosine monophosphate deaminase (AMPD). Assessing skeletal muscle AMPD from both Richardson's ground squirrels (Urocitellus richardsonii) (RGS) and 13-lined ground squirrels (Ictidomys tridecemlineatus) (TLGS), the present study shows that muscle AMPD of euthermic versus hibernating animals displays markedly different kinetic properties, differential responses to temperature and to effectors, and is regulated by reversible protein phosphorylation. AMPD activity decreased during hibernation in both TLGS and RGS skeletal muscle, by 70 and 84%, respectively. Stimulation of total protein phosphatases, total serine/threonine protein phosphatases, PP1, PP2B or PP2C, all reduced AMPD activity between 54 and 92% in extracts of euthermic RGS muscle. The same incubation did not change the activity of AMPD from muscle of hibernating animals. Oppositely, both euthermic and hibernating AMPD showed a strong increase in activity when incubated under conditions that promoted the enzyme phosphorylation by PKA, PKC or PKG. Overall, the data indicate that both low activity of AMPD and low affinity of the enzyme for AMP during torpor reduce the rate of adenylate degradation, the primary driver of these changes being covalent phosphorylation of AMPD.

Not only intoxications of aflatoxins are significant risk for human beings, but also; the contamination with these toxins affect the economy. Therefore, developing a rapid, precise and inexpensive determination method is vitally important. Here, a colorimetric aptasensor is introduced for the detection of aflatoxin M1 (AFM1) based on the preservation of gold nanoparticles (AuNPs) against NaCl-induced aggregation by detaching of complementary strand of aptamer (CS) from the aptamer-modified streptavidin coated silica nanoparticles (SNPs) following the addition of target. So, the color of sample remains red. While, in the lack of AFM1, salt-induced aggregation of AuNPs occurs and the color of sample becomes purple as the aptamer/CS (dsDNA)-modified SNPs is stable and CS cannot bind to AuNPs. The proposed aptasensor could detect AFM1 in a linear dynamic range, 300–75,000 ng/L, with a detection limit of 30 ng/L. Also, the sensing method was effectively applied for AFM1 recognition in milk samples.

Misuse of antibiotics in animal husbandry and presence of their residues in animal foods is a serious crisis worldwide and thus, monitoring the level of them in food samples is vital for human health. Herein, a fluorescent aptasensor was developed for highly sensitive quantification of oxytetracycline (OTC) in food samples. This method is based on OTC aptamer conjugated to magnetic beads, functioned as recognition element, complementary strand of OTC aptamer, and PicoGreen (PG) as a sensitive double-stranded DNA (dsDNA) fluorescent dye. Formation of OTC aptamer-magnetic bead conjugate provides the opportunity of sample condensation and separation technology. Additionally, the presence of complementary strand leads to significant fluorescence signal alteration of aptasensor in the presence or absence of target and a noteworthy improvement of the aptasensor sensitivity. In the absence of target, complementary strand could bind to aptamer and form dsDNA on the surface of magnetic bead. As a consequence, adding PG to the sample leads to observation of high fluorescence signal from sample. In contrast, once OTC is added to the sample, it binds to OTC aptamer-magnetic bead complex and prevents hybridization of OTC aptamer and its complementary strand. Hence, after addition of PG to the sample, a weak fluorescence intensity is measured. Under optimized conditions, the linear ranges for OTC detection were 0.2–2 nM and 2–800 nM. The detection limit was calculated to be as low as 0.15 nM for the fabricated aptasensor. Besides the great sensitivity, proposed method demonstrated superior specificity towards OTC once it was used against several antibiotics. More significantly, the recovery rates of OTC in milk ranged from 96.46% to 101.5%, implying the great feasibility of designed sensor as well as its potential to be employed for analysis of OTC in real samples.

Herein, an aptasensor is presented for electrochemical determination of ochratoxin A (OTA) based on nontarget-triggered production of rolling circular amplification (RCA). The surface of gold electrode is modified with thiolated complementary strand of aptamer (CS) as both capture probe and primer and OTA aptamer (Apt) as both sensing molecule and padlock probe (PLP). Following the addition of OTA, Apt/OTA conjugate is formed and detached from the electrode surface. Therefore, no RCA is produced after incubation of the modified electrode with T4 DNA ligase and phi29 DNA polymerase and a sharp current signal occurs. The analytical response ranged from 30 pM to 120 nM with detection limit of 5 pM. The designed aptasensor showed superior analytical performance in comparison with other approaches for OTA detection. Also, the approach exhibited good performance for OTA determination in spiked grape juice samples. The technique presented in this study, can be applied to develop sensors for detecting different toxins by replacing the relevant aptamers and complementary strands.

Regarding side effects of commonly used chemotherapeutic drugs on normal tissues, researchers introduced smart delivery and on-demand release systems. Herein, we applied a bivalent aptamer composed of ATP and AS1411 aptamers for separate targeting and gating of mesoporous silica nanoparticles in a ladder like structure with one bifunctional molecule. First part of the apatmer, AS1411, direct the delivery system to the desired site while the second part, ATP aptamer, opens the pores and release the drug just after penetrance to the cytoplasm ensuring delivery of DOX into the tumor cells. This approach faced the previous challenge of coincident targeting and gating with one aptamer. Our results demonstrated that the proposed nano-system remarkably accumulated in cancer tissue and released the drug in a sustained pattern in cancer cells. It was notably effective for inducing apoptosis in cancer cells and tumor growth inhibition without any significant side effect on normal cells and organs. Moreover, Si-cs-DOX-AAapt improved the mice survival time compared with free doxorubicin and there was no significant change in weight of mice administered with the targeted formulation. This report may open new insight for providing smart delivery systems for successful cancer treatment by introducing separate gating and targeting property by a bivalent aptamer to increase the control over drug release.

Herein, a simple electrochemical aptasensor with the implementation of an oligonucleotide structure is introduced for determination of malachite green (MG) as a fungicide. The oligonucleotide structure is composed of MG aptamer (Apt) and its two complementary strands (CSs). Benefiting from physical barrier and high negatively charged of the oligonucleotide structure, the proposed sensing strategy indicated improved selectivity and sensitivity for MG detection with a detection limit of 0.15 nM. Addition of MG leads to conformational change of Apt sequence, its release from the electrode surface and dismantlement of the oligonucleotide structure. So, [Fe(CN)6]3−/4− as redox marker has high accessibility to the gold electrode surface and the peak current remarkably increases. Also, the aptasensor exhibited great potential for MG detection in tap water. The designed sensing method opens a simple way for ultrasensitive detection of MG in a relatively short time.

Structure-selective light-up dyes are ideal materials for designing label-free DNA-based biosensors and have gained more interest with researchers. In this study, PicoGreen (PG), as a cyanine fluorogenic dye with a low intrinsic fluorescence emission rate, was employed in a design of an aptasensor based on the formation of three-way junction (3WJ) structure to sense tobramycin (TOB), a member of aminoglycoside antibiotic family with a narrow therapeutic index, in a highly sensitive and simple procedure. In fact, the presence of TOB in the assay changes the number of double-stranded sequences in the engineered design, providing the basis for the difference in the intensity of PG fluorescence signal. The designed biosensor showed a wide linear range from 80 nM to 2 µM with a limit of detection (LOD) equal to 21.86 nM in water. Moreover, it was able to determine TOB in human serum, as a complex matrix, in two linear zones of 5–20 µM and 20–300 µM with a LOD of 321.2 nM, with no need for any complicated sample processing, including addition of organic solvents or ultrafiltering, and only through dilution for 40 times with water. Our results indicated that the prepared sensing strategy could be applicable for clinical samples.

The authors report on an aptamer-based electrochemical assay for the insecticide acetamiprid. It is based on the target-induced release of the redox probe Methylene Blue (MB) from the dsDNA formed between aptamer and complementary strand (Apt/CS), exonuclease I (Exo I) and silica nanoparticles coated with streptavidin (SiNP-Streptavidin). MB is detected electrochemically using an unmodified gold electrode. In the presence of acetamiprid, MB is released from the Apt/CS dsDNA and accumulated in the close environment of the gold electrode. This results in a strong electrochemical signal for MB at fairly low working voltage of typically −0.27 V. In the absence of target, however, the SiNP-streptavidin conjugate modified MB-dsDNA remains intact. Hence, the electrochemical signal remains weak. The method displays high selectivity for acetamiprid and a limit of detection as low as 153 pM. The assay was successfully applied to the determination of acetamiprid in (spiked) water and serum samples, with LODs of 161 and 209 pM, respectively.