Acrylamide (ACR) is extensively used in industrial areas and has been demonstrated to induce neurotoxicity via oxidative stress and apoptosis. In this study, we assessed the probable protective ...effects of thymoquinone (TQ), an active constituent of
Nigella sativa
, against ACR-induced neurotoxicity. ACR (50 mg/kg, i.p., for 11 days) and TQ (2.5, 5 and 10 mg/kg, i.p., for 11 days) were administered to rats. On 12th day, gait score was examined and rats were sacrificed. Malondialdehyde (MDA) and reduced glutathione (GSH) contents were determined in sciatic nerve. Furthermore, western blotting was conducted. The exposure of rats to ACR caused severe gait disabilities. The MDA and GSH contents were increased and decreased, respectively. ACR decreased P-ERK/ERK ratio and myelin basic protein (MBP) content, but significantly increased P-JNK/JNK, P-P38/P38, Bax/Bcl-2 ratios and caspase 3 and 9 levels. Concurrently administration of TQ (5 and 10 mg/kg) with ACR, prevented gait abnormalities and meaningfully reduced MDA and elevated the GSH contents. Furthermore, TQ (5 mg/kg) elevated the P-ERK/ERK ratio and MBP content while reduced the P-JNK/JNK, P-P38/P38 ratios and apoptotic markers. MAP kinase and apoptosis signaling pathways were involved in ACR-induced neurotoxicity in rat sciatic nerve and TQ significantly reduced ACR neurotoxicity. TQ afforded neuroprotection, in part, due to its anti-oxidative stress and anti-apoptotic mechanisms.
Abstract In this study, we reported epirubicin (Epi) encapsulated nanoparticles (NPs) formulated with biocompatible and biodegradable poly (lactic-co-glycolic acid) (PLGA) modified with chitosan (CS) ...through a physical adsorption method. Using chitosan, the solubility and surface charge of PLGA was modified to make efficient drug carriers for cancer cells. To improve the anti-tumor efficacy, we developed targeted therapy of tumor cells using a 5TR1 DNA aptamer (Apt) against the MUC1 receptor. To prove the MUC1 receptor-mediated uptake of Epi-PLGA-CS-Apt NPs in the cells, competition experiments were carried out. In vitro experiments, cytotoxicity assay and fluorescence uptake assay demonstrated that fabricated NPs with or without aptamers showed significantly high therapeutic efficiency in MCF7 cells (breast cancer cell) compared with free Epi, while in BALB/c mice bearing C26 cells (murine colon carcinoma cell), targeted NP groups exhibited significant tumor growth inhibition and higher inclination to tumor compared with non-targeted NPs. Hence, our in vivo results revealed that non-targeted NPs may diffuse away from the tumor site and release Epi in the extracellular space and decrease concentration of the drug in the targeted tissue. This study indicated Epi-PLGA-CS-Apt has great potential as a promising nanoplatform for in vivo cancer therapy and could be of great value in medical use.
Display omitted
•Polymersomes are polymeric vesicles that have numerous advantages for theranostic.•Polymersomes are made of various amphiphilic block copolymers.•In this review we summarized the ...preparation methods of polymersomes for codelivery application.•Then we focused on theranostics and also diagnostics polymersomes which can be used for theranostics purposes in the future, based on various imaging probes.
Polymersomes are polymeric vesicles that have numerous advantages for theranostics, the integrated approach of therapeutics and diagnostics. Polymersomes possess core- shell structures which encapsulate hydrophilic molecules in the aqueous compartment and hydrophobic molecules in the bilayer of the vesicles. Polymersomes are made of different amphiphilic block copolymers. Thus, in the process of designing polymersomes, a variety of amphiphilic block copolymers with different molecular weights are used to develop intelligent or sustained released formulations and to modify the stability of the system and bilayer thickness or to functionalize the particle with targeting moieties to improve the delivery efficiency.
In addition, biocompatible and/or biodegradable polymersomes are diverse in size and charge which show low toxicity in vivo. Polymersomes are increasingly being used as platforms for simultaneous drug delivery and imaging and are therefore becoming popular theranostic nanoparticles. This review focuses on the methods of nanoparticle formation when polymersomes for theranostic nanomedicine are engineered. We highlight recent examples of polymersome theranostic systems from literature and their potential for use in the clinic, particularly biodegradable or biocompatible-based NPs.
Exosomes are endosomal-derived vesicles, playing a major role in cell-to-cell communication. Multiple cells secret these vesicles to induce and inhibit different cellular and molecular pathways. ...Cancer-derived exosomes have been shown to affect development of cancer in different stages and contribute to the recruitment and reprogramming of both proximal and distal tissues. The growing interest in defining the clinical relevance of these nano-sized particles in cancers, has led to the identification of either tissue- or disease-specific exosomal contents, such as nucleic acids, proteins and lipids as a source of new biomarkers which propose the diagnostic potentials of exosomes in early detection of cancers. In this review, we have discussed some aspects of exosomes including their contents, applications and isolation techniques in the field of early cancer detection. Although, exosomes are considered as ideal biomarkers in cancer diagnosis, due to their unique characteristics, there is still a long way in the development of exosome-based assays.
•Exosomes are endosomal-derived vesicles, playing a major role in cell-to-cell communication.•Exosomes are considered as ideal biomarkers in cancer diagnosis, due to their unique characteristics.•In this review, we have discussed some aspects of exosomes including their contents, applications and isolation techniques in the field of early cancer detection.
Nucleolin or C23, is one of the most abundant non-ribosomal phosphoproteins of nucleolus. However, in several cancers, nucleolin is highly expressed both intracellularly and on the cell surface. So, ...it is considered as a potential target for the diagnosis and cancer therapy.
Targeting nucleolin by compounds such as AS1411 aptamer can reduce tumor cell growth. In this regard, interest has increased in nucleolin as a molecular target for overcoming cancer therapy challenges. This review paper addressed recent progresses in nucleolin targeting by the G-rich AS1411 aptamer in the field of cancer therapy mainly over the past three years.
•Nucleolin is highly expressed both intracellularly and on the cell surface.•It is considered as a potential target for the cancer diagnosis and therapy.•AS1411 a 26-mer DNA aptamer that binds nucleolin.•This review paper addressed recent progresses in nucleolin targeting by the AS1411.
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.
•A new turn-off fluorescent aptasensor is presented for detection of ampicillin (AMP) at picopmolar level.•The aptasensor is based on PTCDI as an affordable and cheap fluorophore and AuNPs as precipitating agent in centrifugation process.•Simplicity, low-cost and high sensitivity are great advantages of the developed aptasensor.•The detection limit of sensing approach was 29.2 pM for AMP.•The sensing strategy indicated satisfactory results for the detection of AMP in serum samples.
Prostate cancer (PCa) is one of the most prevalent non‐drug delivery system cutaneous malignancies. Undoubtedly, introducing novel treatment options to achieve higher therapeutic index will be ...worthwhile. In this study, we report for the first time, a novel targeted self‐assembled based on PEG‐PLA nanoparticles (PEG‐PLA NPs) containing galbanic acid (GBA) and docetaxel, which was targeted using ((S)‐2‐(3‐((S)‐5‐amino‐1‐carboxypentyl) ureido) pentanedioic acid (ACUPA), a small molecule inhibitor targeting prostate‐specific membrane antigen (PSMA), in prostate cancer cell line. The prepared NPs were characterized by different analytical methods. The MTT assay was used to compare the anti‐proliferation of drugs‐loaded PEG‐PLA NPs and ACUPA‐PEG‐PLA against LNCaP (PSMA+) and PC3 (PSMA−) cells. PEG‐PLA NPs with an average size of 130–140 nm had an enhanced release of GBA and docetaxel at pH 5.5 compared with pH 7.5. Spectrofluorometric analysis suggested that ACUPA‐modified PEG‐PLA could effectively enhance the drug uptake in PSMA+ prostate cancer cells. Cytotoxicity studies showed that the targeted NPs loaded with different concentrations of GBA and fixed concentration of docetaxel (4 nM) have shown higher toxicity (IC50 30 ± 3 µM) than both free GBA (80 ± 4.5 µM) and nontargeted NPs (IC50 40 ± 4.6 µM) in LNCaP cells. Collectively, these findings suggest that ACUPA‐conjugated PEG‐PLA nanosystem containing GBA and docetaxel is a viable delivery carrier for various cancer‐targeting PSMA that suffer from short circulation half‐life and limited therapeutic efficacy.
In this study, we report for the first time, a novel targeted self‐assembled drug delivery system based on PEG‐PLA nanoparticles (PEG‐PLA NPs) containing galbanic acid (GBA) and docetaxel, which was targeted using ACUPA in prostate cancer cell line
In the current study, resveratrol-loaded PLGA nanoparticles targeted with folate were developed in order to protect resveratrol from fast degradation, modify its pharmacokinetics and increase its ...intestinal permeation. Then, the therapeutic efficacy of the prepared system was evaluated in suppression of colon inflammation on TNBS-induced colitis model.
In this regard, resveratrol was encapsulated in PLGA and FA-conjugated PLGA in order to prepare non-targeted (PLGA-RSV) and targeted (PLGA-FA-RSV) platforms, respectively.
Obtained results demonstrated that the prepared formulations encapsulated the resveratrol with high encapsulation efficiency of 90.7% ± 5.1% for PLGA-RSV and 59.1% ± 3.3% for PLGA-FA-RSV. In vitro release experiment showed that the prepared formulations were capable of retaining good amount of resveratrol under the simulated gastric condition (HCl 0.1 N, pH 1.2), while significant amount of resveratrol was released under simulated intestinal condition (PBS, pH 7.4). The trans-well permeability rates through Caco-2 monolayer during 180 min, was determined to be 4.5%, 61% and 99% for resveratrol, PLGA-RSV and PLGA-FA-RSV respectively. The pathological analysis of the rat intestinal sections (hematoxylin & eosin staining) at 7th day post-TNBS colonic inflammation induction illustrated that the oral administrations of FA-PLGA-RSV and PLGA-RSV were able to significantly inhibit the inflammation and reduce neutrophil and lymphocytes accumulation. It is worth noting that the folate-targeted system demonstrated highest efficacy in suppressing colon inflammation.
It could be concluded that the encapsulation of resveratrol into biodegradable folate-targeted PLGA nanoparticles could introduce a potent platform in suppressing colonic inflammation thus offering a great capability for clinical translation.
•Resveratrol-loaded PLGA nanoparticles targeted with folic acid was developed.•The formulation protected resveratrol under the simulated gastric condition.•Significant amount of resveratrol was released under simulated intestinal condition.•Trans-well permeability rates during 180 min, was determined to be 99%.•Oral administrations of the formulation showed good efficacy against colitis in rat.
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.
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.
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.
•Tetracyclines are broad-spectrum antibiotics.•The use of tetracyclines in farming results in their accumulation in food products.•High sensitivity and simple fabrication are the main characteristics of aptasensors.•We have summarized optical and electrochemical tetracycline aptasensors.
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.
In this study, we developed polycarboxylic acid dextran (PCAD)‐coated dendritic mesoporous silica nanoparticles (DMSNs)‐based drug delivery system as an intelligent nanocarrier, which is capable of controlling the doxorubicin (DOX) release.