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We developed a simple and selective fluorescent aptasensor for the detection of oxytetracycline (OTC) using aptamer-conjugated gold nanoparticles (AuNPs) and a complex formed between oxytetracycline and a europium cation. In this study, AuNPs were modified with an OTC aptamer using two methods (Tween and NaCl methods). In the absence of OTC, an OTC-Eu3+ complex binds to the aptamer in the aptamer-conjugated AuNPs to give weak fluorescence emission. However, in the presence of OTC, the aptamer interacts with its target, causing a strong fluorescence emission. Under optimum conditions, the designed method showed high selectivity for OTC and a good linear range to OTC concentration from 15 to 500 nM with a limit of detection (LOD) of 10.6 nM for the NaCl method and linear range over 15–500 nM with an LOD of 8.8 nM for the Tween method. This biosensor was successfully employed to quantify OTC in milk and tablet samples.

Recently, the siderophores have opened new horizons in nanomedicine. The current study aimed to design a theranostic platform based on superparamagnetic iron oxide nanoparticles-pyoverdine (SPION/PVD) conjugates bound to MUC1 aptamer (MUC1Apt) and loaded with doxorubicin (DOX) as an anti-cancer agent. The SPION/PVD complex was covalently conjugated to MUC1Apt and loaded with DOX to prepare a targeted drug delivery system (SPION/PVD/MUC1Apt/DOX). The investigation of cellular cytotoxicity and uptake of formulations by MTT and flow cytometry in both MUC1 positive (C26) and MUC1 negative (CHO) cell lines revealed that MUC1Apt could improve both cellular uptake and toxicity in the C26 cell line. The evaluation of tumor-targeting activity by in vivo bio-distribution showed that the targeted formulation could enhance tumor inhibitory growth effect and survival rate in C26 tumor-bearing mice. Furthermore, the potential of synthesized SPION/PVD/MUC1Apt/DOX complex as diagnostic agents was investigated by magnetic resonance imaging (MRI) which improved the contrast of tumor site in MRI. Our findings confirm that aptamer-targeted PVD chelated the SPION as a diagnostic agent and loaded with DOX as a chemotherapeutic drug, would be beneficial as a novel theranostic platform.

In recent years, many stimuli-triggered drug delivery platforms have been designed to deliver drugs accurately to specific sites and reduce their side effects, improving "on-demand" therapeutic efficacy. Adenosine-5'-triphosphate (ATP)-responsive drug delivery methods are examples of these systems that use ATP molecules as a trigger for delivery of therapeutic agents. Since intra- and extra-cellular ATP concentrations are significantly different from each other (1-10 mM and

In this study, a dual-receptor doxorubicin-targeted delivery system based on mesoporous silica nanoparticles (MSNs) modified with mucine-1 and ATP aptamers (DOX@MSNs-Apts) was developed. An amine-modified mucine-1 (MUC1) aptamer was covalently anchored on the surface of carboxyl-functionalized MSNs. Then, ATP aptamers (ATP1 and ATP2 aptamers) were immobilized on the surface of MSNs through partial hybridization with the MUC1 aptamer by forming a Y-shaped DNA structure on the MSNs surface (DOX@MSNs-Apts) as a gatekeeper. The developed DOX@MSNs-Apts exhibited high DOX loading capacity. In addition, it indicated an ATP-responsive feature, leading to the release of DOX in the environment with high ATP concentration (10 mM), similar to the intracellular environment of tumor cells. This property demonstrated that anticancer drug (DOX) could be entrapped inside the nanocarrier with nearly no leakage in blood and a very low concentration of ATP (1 μM). It was found that after the internalization of DOX@MSNs-MUC1 by cancer cells via the MUC1 receptor-mediated endocytosis, the ATP aptamers left the surface of the nanocarrier, allowing for rapid DOX release. DOX@MSNs-Apts indicated higher cellular uptake in MCF-7 and C26 cancer cells (MUC1+), rather than CHO cells (MUC1-). The in vitro cytotoxicity and the in vivo antitumor efficacy of DOX@MSNs-Apts showed greater cytotoxicity than the nanoparticles decorated with scrambled ATP aptamers (DOX@MSNs-Apts scrambled) in C26 and MCF-7 cell lines (MUC1+). The biodistribution and in vivo anticancer efficacy on the C26 tumor bearing mice indicated that the DOX@MSNs-Apts had a higher tumor accumulation and superior tumor growth inhibitory effect compared to free DOX and their scrambled aptamers, DOX@MSNs-Apts scrambled. Overall, the obtained results indicated that the prepared smart platform could reveal new insights into the treatment of cancer.

Programmed cell death protein 1 (PD1; also known as CD279) is an inhibitory receptor on T lymphocytes interacting with PD1-ligand 1 and PD1-ligand 2 in the synapse of T cells and antigen presenting cells (APC) resulting in the suppression of T cell activity. Systematic evolution of ligands by exponential enrichment (SELEX) is a method for generating aptamers which can bind specifically to the target of interest. PD-1 antagonistic aptamers could introduce an attractive alternative over the antibody-based treatments due to the distinguished advantages of aptamers including small size and efficient tissue penetration, low cost, lack of immunogenicity, and ease of manufacturing.

This study demonstrated a chemotherapy drug-free delivery system for breast cancer treatment based on a simple DNA nanostructure composed of sequence 1 containing ATP and AS1411 aptamers and sequen...

Nucleolin, an RNA binding protein, is considered to be a target for developing cancer therapies and diagnostics. Herein, we have reported a designed nucleolin-targeted AS1411 aptamer conjugated to guanidinium groups of epibromohydrin functionalized TiO2@γ-Fe2O3 nanoparticles (AS1411@GMBS@EG@TiO2@Fe2O3, NP–Apt) to increase drug delivery in targeted tumor tissues. The structure and morphology of the obtained NPs were characterized by FT-IR, VSM, EDX, HRTEM, and TEM analysis. Doxorubicin (DOX) was entrapped in NP–Apt (NP–Apt–DOX) with an entrapment efficiency of 47.59 ± 3.98%. NP–Apt–DOX revealed homogeneous characteristics with narrow particle size distributions. The in vitro drug release of NP–Apt–DOX was pH-dependent with initial rapid release (within 6 h) followed by sustained release for 72 h. Fluorescence microscopy and MTT assay were used to assess the cellular uptake and anti-proliferation activity of NP–Apt–DOX against nucleolin-positive (A375 and C26) cells. NP–Apt–DOX showed higher cellular uptake and more enhanced cytotoxicity in nucleolin-expressing cancer cells than in L929 fibroblasts as a nucleolin-negative cell line through increasing intracellular ROS levels. Significant tumor growth inhibition and prolonged animal survival were observed in mice bearing C26 colon carcinoma treated with NP–Apt–DOX. Overall, AS1411@GMBS@EG@TiO2@Fe2O3 is a pH-responsive sustained release system and offers promise as an effective and safe system for targeted drug delivery.

Aflatoxin food contamination with toxic and carcinogenic impacts on human health is a global concern. We have developed aptasensors for the detection of Aflatoxin M1 (AFM1) and B1 (AFB1) using electrochemical and optical methods. In the first method, an electrochemical aptasensor was designed for the detection of AFM1 based on complementary strand of AFM1 aptamer that was attached onto the gold nanoparticles and a hairpin-shaped AFM1 aptamer. The designed electrochemical aptasensor showed high selectivity toward AFM1 with a limit of detection (LOD) as low as 0.9 nM. Moreover, the developed aptasensor was successfully used to detect AFM1 in milk and serum with LODs of 1.8 and 1.2 nM, respectively. In the second method, a novel electrochemical aptasensor was developed based on the π-shape structure of AFB1 aptamer. The detection limit was found to be 2 pg/mL in buffer. Also, the developed aptasensor was used to analyze AFB1 spiked human serum and grape juice samples, and the recoveries were 95.4-108.1%. In another method, a fluorescent sensing scheme was developed for AFB1 detection based on a hairpin structure of G-quadruplex oligonucleotide-aptamer chimera, streptavidin-coated silica nanoparticles (SNP-streptavidin) and N-methyl mesoporphyrin IX (NMM). The LOD was reported as 8 pg/mL with a linear range of 30-900 pg/mL. Moreover, the developed sensor could detect AFB1 in serum and grape juice with the LOD of 9.8 and 11.2 pg/mL, respectively.

In this research, a facile fluorescence aptasensor was designed for the ultrasensitive determination of ethanolamine (ETA) as an aliphatic amino alcohol molecule with harmful side effects for human health. Zeolitic imidazolate framework-8 (ZIF-8) as an efficient metal-organic framework was applied to quench the fluorescence emission of the FAM-labeled ETA aptamer. The presence of ETA could recover the fluorescence response under the optimal experimental conditions. ETA could be sensitively detected by the designed aptasensor in the linear concentration range of 0.1 nM-20 µM with the detection limit of 14.38 pM. The designed aptasensor was utilized to determine ETA in milk and serum samples with the detection limits of 17.86 and 15.21 pM, respectively. The aptasensor with the remarkable features of high sensitivity, simplicity and feasibility holds the supreme potential to construct a low-cost portable sensing method for food safety control, human diagnostics, and environmental monitoring with coupling to the microfluidic paper-based devices.

Alzheimer's disease (AD) as common late-life dementia is pathologically associated with the irreversible and progressive disorder, misfolding, deposition, and accumulation of the brain proteins. Especially, the formation of fibrous amyloid plaques by aggregation of amyloid-β peptides is the pathological cause of this neurologic disorder disease. Besides, tau protein isoforms destabilize the microtubule filaments through post-translational modifications and induce nerve cells' death. Amyloid-β peptides and tau proteins are considered as the critical symptom and reliable molecular biomarkers for the early diagnosis of AD. AD is characterized by impaired thinking proficiencies, cognitive decline, memory loss, and behavioral disability. Since there is no efficacious therapy for AD at present, the development of precise sensing tools for the early diagnosis of this disease is essential and crucial. Aptamer-based biosensors (aptasensors) have acquired utmost importance in the field of AD healthcare, due to excellent sensitivity and specificity, ease-of-use, cost-effectiveness, portability, and rapid assay time. Here, we highlight the recent developments and novel perspectives in the field of aptasensor design to quantitatively monitor the AD biomarkers. Finally, some results are represented to achieve a promising viewpoint for introducing the novel aptasensor test kits in the future.

Herein, a simple electrochemical sensor is proposed for 17β-estradiol (E2) determination. In this sensing platform, split DNA aptamers for E2 were applied as recognizing agents. In the presence of E2, split aptamers are bound to E2 and establish split1-E2-split2 complex as a bridge on the surface of electrode. This physical bar leads to ultrasensitive detection of E2. This aptasensor is capable of recognizing E2 within 30 min without complicated procedures and expensive equipment. This sensing approach indicated a wide linear range with detection limits of 0.5 pM and 0.7 pM for E2 in tap water and milk samples, respectively. Simplicity and high specificity of the proposed electrochemical aptasensor make it an ideal sensing platform for ultra-low detection of other targets in complicated samples by replacement of split DNA aptamers.

In this study, the chemical features of dendritic mesoporous silica nanoparticles (DMSNs) provided the opportunity to design a nanostructure with the capability to intelligently transport the payload to the tumor cells. In this regard, doxorubicin (DOX)-encapsulated DMSNs was electrostatically surface-coated with polycarboxylic acid dextran (PCAD) to provide biocompatible dextran-capped DMSNs (PCAD-DMSN@DOX) with controlled pH-dependent drug release. Moreover, a RNA aptamer against a cancer stem cell (CSC) marker, CD133 was covalently attached to the carboxyl groups of DEX to produce a CD133-PCAD-DMSN@DOX. Then, the fabricated nanosystem was utilized to efficiently deliver DOX to CD133+ colorectal cancer cells (HT29). The in vitro evaluation in terms of cellular uptake and cytotoxicity demonstrated that the CD133-PCAD-DMSN@DOX specifically targets HT29 as a CD133 overexpressed cancer cells confirmed by flow cytometry and 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assay. The potentially promising intelligent-targeted platform suggests that targeted dextran-capped DMSNs may find impressive application in cancer therapy.

Detection and quantitation of bisphenol A (BPA) level in food samples and environment are of great significance. In this research work, a new electrochemical aptasensor was developed for ultrasensitive detection of BPA, based on MWCNT/SiO2@Au nanocomposite. Molecular dynamic (MD) simulation was carried out in order to better understand the interaction between the target molecules and the aptamer from molecular point of view. The detection strategy of the proposed electrochemical aptasensor, is based on [Fe (CN)6]3-/4- as a label free redox probe. In the absence of BPA molecules, the aptamers remain unfold so that the long tunnels for receiving the [Fe (CN)6]3-/4- redox probe are formed at the surface of the electrode. But, upon addition of BPA molecules, strong interactions between the BPA molecules and the aptamer are occurred. Therefore, the entrance of the tunnels is closed which results in a hard electron exchange between the redox probe and the electrode surface. Therefore, the electrochemical signal is decreased in the presence of BPA molecules. The proposed electrochemical aptasensor shows a high selectivity toward BPA molecules with a limit of detection (LOD) as low as 10 pM. The fabricated electrochemical aptasensor was successfully applied for detection of BPA in food samples.

Herein, an electrochemical aptasensor is described for detection of ampicillin (Ampi). The sensing strategy is based on the application of a ladder-shaped DNA structure as a multi-layer physical block on the surface of gold electrode. Attributing to the electrostatic repulsion and physical prevention of the ladder-shaped DNA structure, ultrasensitive detection of Ampi was achieved with a detection limit as low as 1 pM. In the presence of Ampi, the ladder-shaped DNA structure is disassembled and detached from the electrode surface. This leads to the high access of [Fe(CN)6]3-/4- as a redox indicator to the electrode surface and a strong redox peak. The aptasensor response for Ampi detection was in the linear range from 7 pM to 100 nM with the detection limit of 1 pM. The presented analytical strategy showed its application in detecting Ampi in the spiked milk samples with satisfactory performance. This work can be easily expanded for different targets by alternating the corresponding aptamers.

Tacrolimus (TAC) acts as an inhibitor of calcineurin, which inhibits the production of interleukin-2. In this study, we aimed to design a targeted delivery platform with poly (lactide-co-glycolide; PLGA) nanoparticles modified with chitosan (CS) and CD8AP17s aptamer (Apt). MOLT-4 cells as CD8 positive and JURKAT cells as CD negative were adopted to investigate the efficacy of the proposed delivery system in vitro. The particle size and Ζ potential of the TAC-PLGA-CS-Apt nanocomplex were 345 nm and 13.7 mV, respectively. Release study showed an efficient TAC release from complex in citrate buffer (pH 5.5). The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay showed that TAC-PLGA-CS-Apt nanocomplex was highly selective toward MOLT-4 cells. Complex increased the cellular uptake of TAC in MOLT-4 cells (target) while reducing its cytotoxicity in JURKAT cells (nontarget). Our study showed that complex nanoconjugate could efficiently deliver TAC into MOLT-4 cells as a model of cytotoxic T cell and it could be considered as a potential candidate for TAC delivery.

Conventional chemotherapy suffers from several drawbacks, including toxic side effects together with the development of resistance to the chemical agents. Therefore, exploring alternative therapeutic approaches as well as developing targeted delivery systems are in demand. Oligonucleotide-based therapy has emerged as a promising and alternative procedure for treating malignancies involving gene-related diseases. In the current study, a targeted delivery system was designed to target cancer cells based on two biocompatible polymers of poly (β amino ester) (PβAE) and poly (d, l-lactide-co-glycolide) (PLGA). In this system, antimir-21 as an inhibitor of microRNA-21 (miR-21) which is an oncomiR overexpressed in several human cancers was condensed with PβAE polymer and then PLGA was electrostatically deposited on this complex and provided a reservoir for positively charged drug, epirubicin (Epi). At the final stage, MUC1 aptamer as a targeting agent was covalently attached to the nanoparticles for selectively guided therapeutic delivery. The obtained results demonstrated that the fabricated MUC1 aptamer-modified nanocomplex could efficiently be internalized into MCF7 (human breast carcinoma cell) and C26 (murine colon carcinoma cell) cells through interaction between MUC1 aptamer and its receptor on the surfaces of these cell lines and decline cell viability in these cells but not in CHO cells (Chinese hamster ovary cell) as nontarget cells (MUC1 negative cells). The safety of PLGA-Epi-PβAE-antimir-21 nanocomplex and synergetic effect of Epi and antimir-21 in reducing cell viability of target cells were confirmed by treating MCF-7 and CHO cells with nanocomplex and MUC1 aptamer-modified nanocomplex. Moreover, it was demonstrated that MUC1 aptamer-modified nanocomplex could remarkably inhibit tumor growth in tumor-bearing mice compared with Epi alone.

Single-stranded DNA aptamers recognizing CD70 molecule overexpressed in some tumor cell lines was isolated by means of systematic evolution of ligands by exponential enrichment (SELEX). Both purified CD70 protein and CD70-expressing cells were used to isolate target-specific aptamer. After certain rounds of protein-based SELEX and cell-SELEX (ten and seven rounds, respectively), Aptamer 928 (hereafter Apt928) with high affinity and specificity for CD70 was obtained. The specific binding of the aptamer to its target could block interaction of CD70 with CD27 (known as CD70 receptor). Dissociation constant of Apt928 was calculated to be 66 nmol L−1. Moreover, ATTO 674N-labeled Apt928 was applied as a fluorescent aptasensor for rapid and sensitive detection of SKOV-3 cells as CD70-positive cells. The detection limit of this aptasensor was 14 cells mL−1.

To explore the effect of combination therapy of epirubicin (Epi) and melittin (Mel) to cancer cells, calcium carbonate nanoparticles (CCN), as carriers, were developed which were modified with MUC1-Dimer aptamers as targeting agents. Both Epi and Mel were delivered at the same time to cancer cells overexpressing the target of MUC1 aptamer, mucin 1 glycoproteins (MCF7 and C26 cells). CCN were prepared with a water-in-oil emulsion method. Epi and Mel were separately encapsulated in CCN and the nanoparticles were modified with MUC1-Dimer aptamers. In vitro studies, including MTT assay, flow cytometry analysis and fluorescence imaging were applied to investigate the targeting and cell proliferation inhibition capabilities of MUC1-Dimer aptamer-CCN-Mel complex and MUC1-Dimer aptamer-CCN-Epi complex in the target (MCF-7 and C26 cells) and nontarget (HepG2) cells. Also, the function of the developed complexes was analyzed using in vivo tumor growth inhibition. The release of Epi from MUC1-Dimer aptamer-CCN-Epi complex was pH-sensitive. Cellular uptake studies showed more internalization of the MUC1-Dimer aptamer-CCN-Epi complex into MCF-7 and C26 cells (target) compared to HepG2 cells (nontarget). Interestingly, the MUC1-Dimer aptamer-CCN-Mel complex and MUC1-Dimer aptamer-CCN-Epi complex indicated very low toxicity as compared to target cells. Moreover, co-delivery of Epi and Mel using the mixture of MUC1-Dimer aptamer-CCN-Mel complex and MUC1-Dimer aptamer-CCN-Epi complex exhibited strong synergistic cytotoxicity in MCF-7 and C26 cells. Furthermore, the presented complexes had a better function to control tumor growth in vivo compared to free Epi.

Ochratoxin A (OTA) as the most dangerous mycotoxin is produced by Aspergillus Ochraceus and Penicillium verrucosum. OTA can be found in beverages and foodstuffs that induces the teratogenic, nephrotoxic, carcinogenic, and immunosuppressive effects on humans. Hence, developing highly sensitive methods for its detection is of great importance. Herein, a novel aptasensor was designed for the label-free monitoring of the ultra-low OTA levels by a combination of the superiority of aptamers and long-range orientational order of liquid crystals (LCs). The aptasensing strategy was based on the conformational switch of the immobilized π-shaped DNA structure on the glass substrate in presence of the target. A shift in the orientation of LCs from random to homeotropic state led to the apparent alteration of the optical appearance of the aptasensor platform from bright to dark. The LC-based aptasensor especially detects OTA at the ultra-trace level as low as 0.63 aM with comparable selectivity. The aptasensor could detect OTA successfully in the grape juice, coffee, and human serum samples. The LC-based aptasensor paves a way for developing portable and real-time sensing probes with high performance for food safety control and clinical application.

Biosensor technology is considered to be a great alternative in analytical techniques over the conventional methods. Among many recently developed techniques and devices, aptasensors are interesting because of their high specificity, selectivity and sensitivity. Combining aptamer as a biological recognition element with gold nanoparticles (AuNPs) as probe, are becoming more general owing to their beneficial properties, including low cost and ability to analyze specific targets on-site and using naked eye. Hydrogen bonds, nucleic acid hybridization, aptamer-target and antigen-antibody binding, Raman signature, enzyme inhibition, and enzyme-mimicking activity are main different sensing strategies exploited in AuNPs-based optical aptasensors. In this review article, we discussed the recent advances in optical aptasensors with a special emphasis on the catalytic activity property of AuNPs.

In spite of huge developments in cancer treatment, versatile combinational formulations of different chemotherapeutic agents to enhance anticancer activity while reducing systemic toxicity still remains a challenge. In this regard, in the current study, an amphiphilic hyaluronic acid-b-polycaprolactone diblock copolymer was synthesized using “click chemistry”. The synthesized copolymer was self-assembled to form polymersomal structures for co-encapsulation of hydrophilic doxorubicin (DOX) and hydrophobic camptothecin (CPT) in their interior aqueous compartment and their bilayer, respectively with 1:10 and 1:1 ratios. The prepared polymersomal combinational formulation surrounded by hyaluronic acid brush as hydrophilic segment, could provide active targeting of the system against CD44 marker expressed on the surface of cancerous cells. The hyaluronic acid shell could also provide flexible chemistry for the conjugation of therapeutic FOXM1-specific DNA aptamer (Forkhead Box M1; against transcription factor FOXM1) on the surface of polymersomes in order to further suppress cancerous cell proliferation. The obtained results demonstrated that the prepared co-formulation provided sustained, controlled release of the entrapped drugs during 200 h. In vitro cytotoxicity experiments on non-small cell lung cancer, A549 and SK-MES-1 cell lines, demonstrated that the co-formulation of DOX and CPT provided synergistic effect and significantly higher cytotoxicity in comparison with free drugs. The cytotoxicity experiment also indicated that the aptamer conjugation on the co-formulations surface could significantly increase the cytotoxicity and induce apoptosis in combination therapy on both A549 and SK-MES-1 cell lines while aptamer-conjugated blank NPs did not show any cytotoxicity which emphasizes on the sensitization capability of the FOXM1 DNA aptamer against non-small cell lung cancer. Furthermore, it was shown that the co-formulation with or without aptamer renders the formulation specific tumor accumulation in vivo 24 h post-administration, assisting the combination synergy observed in vitro to be translated to in vivo antitumor efficacy. This combinatorial delivery platform strongly offers a novel approach for the synergistic controlled transportation of several chemotherapeutics for the treatment of non-small cell lung cancer.

In this study, we synthesized PLA-PEI micelles which was co-loaded with an anticancer drug, camptothecin (CPT), and survivin-shRNA (sur-shRNA). The hydrophobic CPT was encapsulated in the core of the polymeric micelles while sur-shRNA was adsorbed on the shell of the cationic micelles. Then, the positively-charged sur-shRNA-loaded micelles were coated with poly carboxylic acid dextran (PCAD) to form PLA/PEI-CPT-SUR-DEX. To selectively target the system to colon cancer cells, AS1411 aptamer was covalently attached to the surface of the PCAD-coated nanoparticles (PLA/PEI-CPT-SUR-DEX-APT). PLA/PEI-CPT-SUR-DEX-APT enhanced cellular uptake through receptor-mediated endocytosis followed by increased CPT accumulation, downregulation of survivin, and thereby 38% cell apoptosis. In C26 tumor-bearing mice models, after administered intravenously, PLA/PEI-CPT-SUR-DEX-APT and PLA/PEI-CPT-SUR-DEX formulations resulted in a significant inhibition of the tumor growth with tumor inhibition rate of 93% and 87%, respectively. Therefore, PLA/PEI-CPT-SUR-DEX-APT could be a versatile co-delivery vehicle for promising therapy of colorectal cancer.

Herein, a novel turn-off fluorescent aptasensor was developed for selective detection of ampicillin (AMP) at picomolar level based on 3,4,9,10-perylenetetracarboxylic acid diimide (PTCDI) as an affordable and low-cost fluorophore. This aptasensor was designed using aptamer, its complementary strand (CS) and gold nanoparticles (AuNPs). The principle of the sensing method is a decrease in the fluorescence intensity of PTCDI in the presence of free CS. Following the addition of AMP, Aptamer/CS-modified AuNPs releases CS and so, the fluorescence intensity of PTCDI is reduced. The designed analytical method indicated a good linear range from 100 pM to 1000 pM and a limit of detection (LOD) of 29.2 pM was obtained. Furthermore, the sensing strategy indicated satisfactory results for the detection of AMP in the spiked human serum samples. By changing the sequences of aptamer and its CS, the presented analytical approach can be easily applied for detection of other antibiotics.

Breast cancer is the second leading cause of cancer deaths in women and, due to its diverse morphological features, variable clinical outcome and response to different therapeutic options, is known as a highly heterogeneous disease. Aptamers are a class of therapeutic oligonucleotides that are rapidly generated through the SELEX (Systematic Evolution of Ligands by EXponential enrichment) process. The unique properties of aptamers such as high binding affinity and selectivity, low or no immunogenicity and toxicity, low cost and thermal stability make them good potential pharmaceutical agents. In this review, we present the recent progress of aptamer application in targeted delivery systems for imaging and treatment of breast cancer. Furthermore, some analytical approaches such as electrochemical and optical aptasensors are introduced for the detection and diagnosis of breast cancer. Finally, we discuss the problems and challenges of aptamer application in this field.

In recent years, many stimuli-triggered drug delivery platforms have been designed to deliver drugs accurately to specific sites and reduce their side effects, improving “on-demand” therapeutic efficacy. Adenosine-5'-triphosphate (ATP)-responsive drug delivery methods are examples of these systems that use ATP molecules as a trigger for delivery of therapeutic agents. Since intra- and extra-cellular ATP concentrations are significantly different from each other (1-10 mM and

In this study, a novel colorimetric sensor was introduced to detect tobramycin (TOB) based on controlling the catalytic activity of gold nanoparticles (AuNPs) by the three-way junction aptamer pockets. In the absence of TOB, the surfaces of AuNPs were masked by the three-way junction pockets that prevented their catalytic activation for the reduction of 4-Nitrophenol in the presence of NaBH4. While the formation of the pockets was prevented in the presence of TOB that facilitated the 4-Nitrophenol access to AuNPs. Hence, the catalytic reduction of 4-Nitrophenol induced a color change of the solution from yellow to colorless, highlighting the presence of the target. The aptasensing assay provided good target specificity with a detection limit (LOD) of 1.16 µM and a linear dynamic range over 4-32 µM. The aptasensor was successfully applied to quantitatively monitor TOB in the human serum and milk samples with the LODs of 1.38 and 1.42 µM and recovery values of 94.87-105.75% and 93.75-105.31%, respectively.

As one of the most toxic mycotoxins, aflatoxin B1 (AFB1) is a major food pollutant which can pose a high risk to human health. In this work, an accurate fluorescent sensing method was proposed for AFB1 determination, based on hairpin structure of G-quadruplex oligonucleotide-Aptamer chimera, silica nanoparticles coated with streptavidin (SNPs-Streptavidin) and N-methyl mesoporphyrin IX (NMM). The hairpin structure of chimera and SNPs-Streptavidin allowed AFB1 detection with high sensitivity and specificity. Moreover, the developed sensor could detect AFB1 in 30 min. The relative fluorescence intensity increased as AFB1 concentrations increased with a linear range of 30–900 pg/mL and a limit of detection (LOD) of 8 pg/mL. The constructed aptasensor was successfully employed to assess AFB1 spiked grape juice and human serum samples. The analytical recovery of AFB1 in the grape juice samples ranged from 95 to 106%, implying the great potential of the presented aptasensor in food product analysis.

Kanamycin is an aminoglycoside antibiotic that can be useful against both gram negative and positive bacteria. However, if its serum levels are not controlled properly, it can cause serious side effects like ototoxicity and nephrotoxicity. The aim of this study was to design a simple and rapid fluorescent aptasensor for detection of kanamycin, based on Aptamer/Complementary strand (dsDNA)-capped mesoporous silica nanoparticles (MSNs) and Rhodamine B as a fluorescent probe. The MSNs pores were filled with Rhodamine B and then gated with dsDNA. In the presence of kanamycin, the aptamer sequence was separated from its complementary strand (CS), so that, uncovered the pores and leading to leakage of Rhodamine B. Thus, a significant increase in the fluorescence intensity was observed. The relative fluorescence intensity showed a linearity range from 24.75 nM to 137.15 nM of kanamycin with a detection limit of 7.5 nM. The aptasensor also showed to be useful for detection of kanamycin in serum samples and was able to distinguish kanamycin from other antibiotics, resulting in a sensitive, rapid and inexpensive method for kanamycin detection.

Systematic evolution of ligand by exponential enrichment (SELEX) is an efficient method used to isolate high-affinity single stranded oligonucleotides from a large random sequence pool. These SELEX-derived oligonucleotides named aptamer, can be selected against a broad spectrum of target molecules including proteins, cells, microorganisms and chemical compounds. Like antibodies, aptamers have a great potential in interacting with and binding to their targets through structural recognition and are therefore called “chemical antibodies”. However, aptamers offer advantages over antibodies including smaller size, better tissue penetration, higher thermal stability, lower immunogenicity, easier production, lower cost of synthesis and facilitated conjugation or modification with different functional moieties. Thus, aptamers represent an attractive substitution for protein antibodies in the fields of biomarker discovery, diagnosis, imaging and targeted therapy. Enormous interest in aptamer technology triggered the development of SELEX that has underwent numerous modifications since its introduction in 1990. This review will discuss the recent advances in SELEX methods and their advantages and limitations. Aptamer applications are also briefly outlined in this review.

Tuberculosis is a major global health problem caused by the bacterium Mycobacterium tuberculosis (Mtb) complex. According to WHO reports, 53 million TB patients died from 2000 to 2016. Therefore, early diagnosis of the disease is of great importance for global health care programs. The restrictions of traditional methods have encouraged the development of innovative methods for rapid, reliable, and cost-effective diagnosis of tuberculosis. In recent years, aptamer-based biosensors or aptasensors have drawn great attention to sensitive and accessible detection of tuberculosis. Aptamers are small short single-stranded molecules of DNA or RNA that fold to a unique form and bind to targets. Once combined with nanomaterials, nano-scale aptasensors provide powerful analytical platforms for diagnosing of tuberculosis. Various groups designed and studied aptamers specific for the whole cells of M. tuberculosis, mycobacterial proteins and IFN-γ for early diagnosis of TB. Advantages such as high specificity and strong affinity, potential for binding to a larger variety of targets, increased stability, lower costs of synthesis and storage requirements, and lower probability of contamination make aptasensors pivotal alternatives for future TB diagnostics. In recent years, the concept of SOMAmer has opened new horizons in high precision detection of tuberculosis biomarkers. This review article provides a description of the research progresses of aptamer-based and SOMAmer-based biosensors and nanobiosensors for the detection of tuberculosis.

In this study, a novel electrochemical aptasensor was developed for detection of AFM1 aflatoxin M1 (AFM1) based on the hairpin-shaped structure of AFM1 aptamer (Apt), gold nanoparticles (AuNPs) and complementary strand of the aptamer (CS). The conformational change of hairpin structure of Apt in the presence and absence of AFM1 and also negatively charged AuNPs allowed detection of AFM1 with high sensitivity and selectivity. In the absence of the AFM1, the hairpin structure of the Apt was intact. So, a weak peak current was obtained. However, addition of AFM1 could disassemble the hairpin structure of the Apt. Thus, the CS-modified AuNPs came to close proximity of the surface of electrode and a strong current signal was recorded upon the addition of methylene blue as redox agent. The aptasensor allowed determination of AFM1 with a detection limit of 0.9 ng/L. Finally, the aptasensor was successfully applied for detection of AFM1 in real samples, including milk and serum samples.

Herein, a novel colorimetric aptasensor was introduced for detection of cocaine based on the formation of three-way junction pockets on the surfaces of gold nanoparticles (AuNPs) and the catalytic activity of the surfaces of AuNPs. Simplicity and detection of cocaine in a short time (only 35 min) are some of the unique features of the proposed sensing strategy. In the presence of cocaine, triple-fragment aptamer (TFA) forms on the surfaces of AuNPs, leading to a significant decrease of the catalytic activity of AuNPs and the color of samples remains yellow. In the absence of target, TFA does not form on the surfaces of AuNPs and 4-Nitrophenol, as a colorimetric agent, has more access to the surfaces of AuNPs, resulting in the reduction of 4-Nitrophenol and the color of sample changes from yellow to colorless. The sensing strategy showed good specificity, a limit of detection (LOD) of 440 pM and a dynamic range over 2–100 nM. The sensing method was also successfully applied to detect cocaine in spiked human serum samples with recovery of 94.71–98.63%.

Vascular endothelial growth factor (VEGF) is a key regulator of vascular formation and a predominant protein biomarker in cancer angiogenesis. Owing to its crucial roles in the cancer metastasis, VEGF detection and quantification is of great importance in clinical diagnostics. Today, there exist a wide variety of detection strategies for identifying many types of disease biomarkers, especially for VEGF. As artificial single-stranded DNA or RNA oligonucleotides with catalytic and receptor properties, aptamers have drawn lots of attention to be applied in biosensing platforms due to their target-induced conformational changes as well as high stability and target versatility. So far, various sensitivity-enhancement techniques in combination with a broad range of smart nanomaterials have integrated into the design of novel aptasensors to improve detection limit and sensitivity of analyte detection. This review article provides a brief classification and description of the research progresses of aptamer-based biosensors and nanobiosensors for the detection and quantitative determination of VEGF based on optical and electrochemical platforms.

Triggering unpredictable allergic reactions associated with the presence of hidden allergens in the food chains have raised the need for precise, fast and reliable analytical methods to identify food allergens in different sources. Unintentional cross contamination of food products with allergen sources during production, transformation or processing is also an important risk factor for triggering allergenic reactions in suspected individuals. Different types of antibody based detection methods are applied for detection and standardization of food-born allergens. Aptamers attracted a great attention because of their small size, low cast and ease of manufacturing. Several detection strategies have been investigated for food allergen aptasensing such as electrochemical, optical, thermometric and piezoelectric. In this review, advances and the future trends of developed aptasensors for the control and detection of food-born allergens have been discussed.

Targeted delivery of DNA nanoparticles is a promising approach in cancer therapy. Using aptamers, target specific delivery of DNA nanoparticles can be achieved. Further, aptamers can indirectly improve drug encapsulation efficiency of DNA nanoparticles for drugs intercalated within nucleic acid base pairs. Using DNA blocks, a micellar hybrid nanoparticle was prepared for the targeted co-delivery of doxorubicin and a pro-apoptotic peptide, KLA to tumor cells. Results demonstrated that anti-MUC1 aptamer could specifically deliver the synthesized DNA micelle into MCF-7 cells by improving its cellular uptake. Additionally, co-delivery of doxorubicin and KLA could significantly enhance the therapeutic efficacy of the construct resulting in reduction of required dose of doxorubicin that is a pivotal point in reducing chemotherapeutics side effects. Moreover, DOX-KLA-anti-MUC1-micelle remarkably inhibited tumor growth of tumor-bearing mice when compared with free drug. DOX-KLA-anti-MUC1-micelle also reduced toxic effect of free doxorubicin as determined by percent of body weight loss and survival rate in vivo.

Background Aptasensors are promising biosensors with prominent recognition capabilities. They have fascinated a lot of attention among scholars, due to the excellent characteristics of aptamers in combination with the use of nanostructures and new interface materials. The high sensitivity and selectivity of such platforms provide a promising view in food analysis. Scope and approach The uncontrolled usage of antibiotics, such as tetracyclines (TCs), results in the accumulation of antibiotics in food products. The traditional analytical method for detection of antimicrobial residues in food products is liquid chromatography coupled to mass spectrometric detection. Today, simple, sensitive and rapid schemes are needed for an on-site screening analysis. However, the routine techniques for TCs detection are not designed for this purpose. This review summarizes electrochemical and optical tetracycline aptasensors in food and buffer samples with focusing on modern methods and recent advances on aptamer-based tetracycline detection methods. Key findings and conclusions Here, we discussed several optical and electrochemical transduction systems and their principles in aptasensor-based tetracycline detection for the first time and we focused on modern methods and recent advances. Although an optical biosensor will always have the advantage of being easier to operate with inexpensive instrument, but electrochemical aptasensors offer higher sensitivity, repeatability and accuracy. Finally, we address current challenges and future directions.

Simple and reliable sensors for detection of arsenic (As), a toxic heavy metal, in drinking water and blood serum are highly desirable. Herein, we reported the fabrication and characterization of a fluorescent aptasensor for the detection of As (III) using target-induced conformational change of the Biotin and FAM-labeled complementary strand of aptamer (CS1), silica nanoparticles coated with streptavidin (SNPs-Streptavidin) and a label-free aptamer (Apt). The sensor described here had several attractive features, such as simplicity, rapid response and use of label-free Apt. Upon addition of As (III), Apt released its CSs and CS1 formed a hairpin structure on the surface of SNPs-Streptavidin, leading to a strong fluorescence signal. Without introduction of As (III), Apt was hybridized with its CSs and a weak fluorescence signal was obtained. The sensor exhibited a wide linear range between 2 and 500 nM and a very low detection limit of 0.45 nM. In addition, the applicability of the developed method was tested using spiked tap water and serum samples with satisfactory results.

Herein, we report a novel approach to design a fluorescent aptasensor for detection of carcinoembryonic antigen (CEA), a tumor marker, using three-way junction pocket and 5,6,7-trimethyl-1,8-naphthyridin-2-amine (ATMND) as a fluorescent agent. The analytical method was based on the entrapment of ATMND in the three-way junction pocket in the absence of CEA, leading to a significant decrease of fluorescence intensity of ATMND. Under, the optimum condition, the relative fluorescence intensity indicated a wide linearity range from 4.5 pg/mL to 30 ng/mL of CEA with a detection limit of 1.5 pg/mL. The aptasensor was also successfully used in human serum for CEA detection, which showed a good recovery (96.1–106.7%). This aptasensor owned several advantages such as simplicity and application of a label-free aptamer.

In regard to tremendous toxicological effects of aflatoxin B1 (AFB1) and its major metabolite aflatoxin M1 (AFM1) on human health, quality assessment of food is of great importance. On the other hand, due to extremely low levels of these toxic metabolites in food and feed, the need to develop reliable and sensitive method is inevitable. Although, very different analytical techniques have been introduced for detection of them, hindrances such as time-consuming, labor-intensive, and highly-priced instruments have limited their uses. Aptasensors, as emerging methods, have opened new horizons for sensitive and selective detection of toxins. Aptamers are a new class of characteristic bio-recognition elements, provided by an in vitro process named SELEX (Systematic Evolution of Ligands by EXponential enrichments). This review discusses aptasensors developed for detection of AFB1 and AFM1. Additionally, we aimed to investigate the advantages and disadvantages of these systems and introduce the best ones.

Melittin, a small water-soluble cationic amphipathic α-helical linear peptide, consisted of 26 amino acids, is the honeybee venom major constituent. Several reports have proved the lytic and apoptotic effects of melittin in several cancerous cell lines. In this study, we aimed to fabricate an AS1411 aptamer-melittin to specifically deliver melittin to nucleolin positive cells (A549). Melittin was covalently attached to antinucleolin aptamer (AS1411) and its toxicity in A549 (nucleolin positive) and L929 (nucleolin negative) was studied using MTT and Annexin V flow cytometry methods. Aptamer-melittin conjugate formation was confirmed by gel electrophoresis. Hemolytic effect of aptamer-melittin conjugate was compared to melittin alone. The aptamer-melittin conjugate showed efficient cell uptake and was more cytotoxic in A549 cells than melittin (p .001). This complex was less toxic in control cells. Competitive inhibition assay confirmed that aptamer-melittin complex delivery occurred through receptor-ligand interaction on the cell surface. Moreover, aptamer-melittin showed a significantly less hemolytic activity as compared with free melittin. This study showed that melittin could be specifically delivered to A549 cells when it was covalently conjugated to antinucleolin aptamer (AS1411) in vitro. This system can reduce the cytotoxic effects of melittin on cells with no nucleolin receptor overexpression which comprise most of normal cells such as L929 cells.

Herein, a sensitive and rapid fluorescent aptasensor was developed for the detection of cocaine as an illicit drug, based on an amplification strategy involving the use of silica nanoparticles coated with streptavidin (SNPs), double quenching of FAM fluorophore and cocaine split aptamer. Presence of cocaine could trigger the formation of the double-fragment cocaine aptamer and bring TAMRA fluorophore near the SNP surface and FAM close to BHQ-1 and TAMRA, resulting in the enhancement of relative fluorescence signal (fluorescence intensity of TAMRA/fluorescence intensity of FAM). Under optimal conditions, the proposed aptasensor achieved a limit of detection (LOD) of 84 pM and a linear range of 500 pM to 80 nM for cocaine. The practical potential of the developed sensing platform was proved by the detection of cocaine in spiked human serum samples with satisfactory recoveries.