Optimization of the photocatalytic degradation of phenol using superparamagnetic iron oxide (Fe3O4) nanoparticles in aqueous solutions.

The present work was carried out to remove phenol from aqueous medium using a photocatalytic process with superparamagnetic iron oxide nanoparticles (Fe3O4) called SPIONs. The photocatalytic process was optimized using a central composite design based on the response surface methodology. The effects of pH (3-7), UV/SPION nanoparticles ratio (1-3), contact time (30-90 minutes), and initial phenol concentration (20-80 mg L-1) on the photocatalytic process were investigated. The interaction of the process parameters and their optimal conditions were determined using CCD. The statistical data were analyzed using a one-way analysis of variance. We developed a quadratic model using a central composite design to indicate the photocatalyst impact on the decomposition of phenol. There was a close similarity between the empirical values gained for the phenol content and the predicted response values. Considering the design, optimum values of pH, phenol concentration, UV/SPION ratio, and contact time were determined to be 3, 80 mg L-1, 3, and 60 min, respectively; 94.9% of phenol was eliminated under the mentioned conditions. Since high values were obtained for the adjusted R2 (0.9786) and determination coefficient (R2 = 0.9875), the response surface methodology can describe the phenol removal by the use of the photocatalytic process. According to the one-way analysis of variance results, the quadratic model obtained by RSM is statistically significant for removing phenol. The recyclability of 92% after four consecutive cycles indicates the excellent stability of the photocatalyst for practical applications. Our research findings indicate that it is possible to employ response surface methodology as a helpful tool to optimize and modify process parameters for maximizing phenol removal from aqueous solutions and photocatalytic processes using SPIONs.

Preparation and Evaluation of the In situ Gel-forming Chitosan Hydrogels for Nasal Delivery of Morphine in a Single Unit dose in Rats to Enhance the Analgesic Responses.

INTRODUCTION: In this study, an in situ gel-forming chitosan hydrogel was prepared with the use of glutamate salt of chitosan (Ch-Ga), ß-glycerophosphate (Gp), and morphine (Mor). The paper is focused on in vitro physicochemical properties and in-vivo analgesic effects of the prepared chitosan hydrogel. METHOD: The thermosensitive properties of prepared chitosan hydrogel were evaluated during the different temperatures and times. The physicochemical properties of chitosan hydrogel were investigated by infrared (IR) spectroscopy and X-ray diffraction analysis (XRD). Also, its cell cytotoxicity effects were evaluated in murine NIH/3T3 normal cells. Subsequently, the distribution of chitosan hydrogel in the nasal cavity of rats and its analgesic responses were evaluated. The prepared chitosan hydrogel showed that it could be gelled at the temperature of 34 °C before leaving the nose in the shortest possible time of 30 s. RESULT: The analgesic responses of the intranasal (IN) injection of chitosan hydrogel (IN-chitosan hydrogel, 10 mg Mor/kg) in a single unit dose in rat relative to the placebo and intranasal or intraperitoneal (IP) injection of free morphine solution (IN-Free Mor or IP-Free Mor, 10 mg Mor/kg) via the hot plate test, reveal that the IN-chitosan hydrogel could induce fast analgesic effects of morphine with maximum possible effect (MPE) of 93% after 5 min compare to the IN-Free Mor and IP-Free Mor with MPE of 80% after 15 min and 66% after 30 min, respectively. Also, prolonged analgesic effects with MPE of 78 % after 6 h of injection were only seen in the IN-chitosan hydrogel injected group. The obtained fluorescent images of rat's brain injected with IN-chitosan hydrogel containing doxorubicine (Dox) as a fluorescent agent showed that the mucosal adhesive and absorption enhancer properties of IN-chitosan hydrogel resulting in longer presence of them in the nasal cavity of rats followed by more absorption of Dox from the blood vessels of olfactory bulbs with a 74% color intensity compared to the IN-Free Mor and IN-Free Dox with 15%. CONCLUSION: These data reveal that the IN-chitosan hydrogel could induce fast and prolonged analgesic effects of morphine compare to the IN/IP-Free Mor, which could be considered as an in situ gel-forming thermosensitive chitosan hydrogel for nasal delivery of wide ranges of therapeutic agents.

Targeted SPION siderophore conjugate loaded with doxorubicin as a theranostic agent for imaging and treatment of colon carcinoma.

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.

Recent developments in targeting genes and pathways by RNAi-based approaches in colorectal cancer.

A wide spectrum of genetic and epigenetic variations together with environmental factors has made colorectal cancer (CRC), which involves the colon and rectum, a challenging and heterogeneous cancer. CRC cannot be effectively overcomed by common conventional therapies including surgery, chemotherapy, targeted therapy, and hormone replacement which highlights the need for a rational design of novel anticancer therapy. Accumulating evidence indicates that RNA interference (RNAi) could be an important avenue to generate great therapeutic efficacy for CRC by targeting genes that are responsible for the viability, cell cycle, proliferation, apoptosis, differentiation, metastasis, and invasion of CRC cells. In this review, we underline the documented benefits of small interfering RNAs and short hairpin RNAs to target genes and signaling pathways related to CRC tumorigenesis. We address the synergistic effects of RNAi-mediated gene knockdown and inhibitors/chemotherapy agents to increase the sensitivity of CRC cells to common therapies. Finally, this review points new delivery systems/materials for improving the cellular uptake efficiency and reducing off-target effects of RNAi.

Fabrication of deferasirox-decorated aptamer-targeted superparamagnetic iron oxide nanoparticles (SPION) as a therapeutic and magnetic resonance imaging agent in cancer therapy.

In the current study, the synthesis of a theranostic platform composed of superparamagnetic iron oxide nanoparticles (SPION)-deferasirox conjugates targeted with AS1411 DNA aptamer was reported. In this regard, SPION was amine-functionalized by (3-aminopropyl)trimethoxysilane (ATPMS), and then deferasirox was covalently conjugated onto its surface. Finally, to provide guided drug delivery to cancerous tissue, AS1411 aptamer was conjugated to the complex of SPION-deferasirox. The cellular toxicity assay on CHO, C-26 and AGS cell lines verified higher cellular toxicity of targeted complex in comparison with non-targeted one. The evaluation of in vivo tumor growth inhibitory effect in C26 tumor-bearing mice illustrated that the aptamer-targeted complex significantly enhanced the therapeutic outcome in comparison with both non-targeted complex and free drug. The diagnostic capability of the prepared platform was also evaluated implementing C26-tumor-bearing mice. Obtained data confirmed higher tumor accumulation and higher tumor residence time for targeted complex through MRI imaging due to the existence of SPION as a contrast agent in the core of the prepared complex. The prepared multimodal theranostic system provides a safe and effective platform for fighting against cancer.

Bispecific monoclonal antibodies for targeted immunotherapy of solid tumors: Recent advances and clinical trials.

Bispecific antibodie (BsAbs) combine two or more epitope-recognizing sequences into a single protein molecule. The first therapeutic applications of BsAbs were focused on cancer therapy. However, these antibodies have grown to cover a wider disease spectrum, including imaging, diagnosis, prophylaxis, and therapy of inflammatory and autoimmune diseases. BsAbs can be categorized into IgG-like formats and non-IgG-like formats. Different technologies have been used for the construction of BsAbs including "CrossMAb", "Quadroma", "knobs-into-holes" and molecular cloning. The mechanism of action for BsAbs includes the induction of CDC, ADCC, ADCP, apoptosis, and recruitment of cell surface receptors, as well as activation or inhibition of signaling pathways. The first clinical trials included mainly leukemia and lymphoma, but solid tumors are now being investigated. The BsAbs bind to a tumor-specific antigen using one epitope, while the second epitope binds to immune cell receptors such as CD3, CD16, CD64, and CD89, with the goal of stimulating the immune response against cancer cells. Currently, over 20 different commercial methods have been developed for the construction of BsAbs. Three BsAbs are currently clinically approved and marketed, and more than 85 clinical trials are in progress. In the present review, we discuss recent trends in the design, engineering, clinical applications, and clinical trials of BsAbs in solid tumors.

Metal-based nanoparticles for bone tissue engineering.

Tissue is vital to the organization of multicellular organisms, because it creates the different organs and provides the main scaffold for body shape. The quest for effective methods to allow tissue regeneration and create scaffolds for new tissue growth has intensified in recent years. Tissue engineering has recently used some promising alternatives to existing conventional scaffold materials, many of which have been derived from nanotechnology. One important example of these is metal nanoparticles. The purpose of this review is to cover novel tissue engineering methods, paying special attention to those based on the use of metal-based nanoparticles. The unique physiochemical properties of metal nanoparticles, such as antibacterial effects, shape memory phenomenon, low cytotoxicity, stimulation of the proliferation process, good mechanical and tensile strength, acceptable biocompatibility, significant osteogenic potential, and ability to regulate cell growth pathways, suggest that they can perform as novel types of scaffolds for bone tissue engineering. The basic principles of various nanoparticle-based composites and scaffolds are discussed in this review. The merits and demerits of these particles are critically discussed, and their importance in bone tissue engineering is highlighted.

Recent progress in the design of DNA vaccines against tuberculosis.

Current tuberculosis (TB) vaccines have some disadvantages and many efforts have been undertaken to produce effective TB vaccines. As a result of their advantages, DNA vaccines are promising future vaccine candidates. This review focuses on the design and delivery of novel DNA-based vaccines against TB.

microRNA-181a mediates the chemo-sensitivity of glioblastoma to carmustine and regulates cell proliferation, migration, and apoptosis.

Glioblastoma multiform (GBM) as the most frequent and lethal brain tumor is defined by aggressive invasiveness and considerable resistance to chemotherapy. The molecular mechanisms underlying GBM tumorigenesis still needs to be further investigated. Considering that, the current study was aimed to investigate the function of miR-181a in human glioblastoma cells in combination with carmustine. U373 cell line with the low expression levels of miR-181a was selected for functional investigations. MTT assay was used to determine cell viability and Annexin V/PI and DAPI staining were employed to evaluate apoptosis induction. Also, cell migration and cell cycle progression were investigated using wound healing test and flow cytometry, respectively. qRT-PCR was used for the quantification of gene expression. MTT assay results revealed that miR-181a replacement increased the sensitivity of U373 cells to low doses of carmustine. Moreover, miR-181a was shown to increase the sub G1 cell cycle arrest and apoptosis induction by carmustine via regulating the expression of related genes including caspase-9, Bcl-2, and SIRT1. Furthermore, this miRNA combined with carmustine suppressed cell migration via downregulation of MMP-2 and Bach1 and reduced the clonogenic ability of U373 cells. Additionally, miR-181a-mediated downregulation of AKT1 implied that this miRNA could inhibit cell proliferation by modulating PI3K/AKT signaling pathway. In conclusion, the findings of this study suggest that miR-181a replacement, regarding its tumor-suppressive effects and sensitization of glioblastoma cells to carmustine, could be considered as a potential therapeutic strategy to improve the efficiency of glioblastoma chemotherapy.

Thrombolytic Agents: Nanocarriers in Controlled Release.

Thrombosis is a life-threatening pathological condition in which blood clots form in blood vessels, obstructing or interfering with blood flow. Thrombolytic agents (TAs) are enzymes that can catalyze the conversion of plasminogen to plasmin to dissolve blood clots. The plasmin formed by TAs breaks down fibrin clots into soluble fibrin that finally dissolves thrombi. Several TAs have been developed to treat various thromboembolic diseases, such as pulmonary embolisms, acute myocardial infarction, deep vein thrombosis, and extensive coronary emboli. However, systemic TA administration can trigger non-specific activation that can increase the incidence of bleeding. Moreover, protein-based TAs are rapidly inactivated upon injection resulting in the need for large doses. To overcome these limitations, various types of nanocarriers have been introduced that enhance the pharmacokinetic effects by protecting the TA from the biological environment and targeting the release into coagulation. The nanocarriers show increasing half-life, reducing side effects, and improving overall TA efficacy. In this work, the recent advances in various types of TAs and nanocarriers are thoroughly reviewed. Various types of nanocarriers, including lipid-based, polymer-based, and metal-based nanoparticles are described, for the targeted delivery of TAs. This work also provides insights into issues related to the future of TA development and successful clinical translation.

microRNA-181 serves as a dual-role regulator in the development of human cancers.

MicroRNAs (miRNAs) as the regulatory short noncoding RNAs are involved in a wide array of cellular and molecular processes. They negatively regulate gene expression and their dysfunction is correlated with cancer development through modulation of multiple signaling pathways. Therefore, these molecules could be considered as novel biomarkers and therapeutic targets for more effective management of human cancers. Recent studies have demonstrated that the miR-181 family is dysregulated in various tumor tissues and plays a pivotal role in carcinogenesis. They have been shown to act as oncomirs or tumor suppressors considering their mRNA targets and to be involved in cell proliferation, apoptosis, autophagy, angiogenesis and drug resistance. Additionally, these miRNAs have been demonstrated to exert their regulatory effects through modulating multiple signaling pathways including PI3K/AKT, MAPK, TGF-b, Wnt, NF-κB, Notch pathways. Given that, in this review, we briefly summarise the recent studies that have focused on the roles of miRNA-181 family as the multifunctional miRNAs in tumorigenesis and cancer development. These miRNAs may serve as diagnostic and prognostic biomarkers or therapeutic targets in human cancer gene therapy.

Recent advances in the application of mesoporous silica-based nanomaterials for bone tissue engineering.

Silica nanomaterials (SNMs) and their composites have recently been investigated as scaffolds for bone tissue engineering. SNM scaffolds possess the ability to encourage bone cell growth and also allow the simultaneous delivery of biologically active biomolecules that are encapsulated in the mesopores. Their high mechanical strength, low cytotoxicity, ability to stimulate both the proliferation and osteogenic differentiation of progenitor cells make the SNMs appropriate scaffolds. Their physiochemical properties facilitate the cell spreading process, allow easy access to nutrients and help the cell-cell communication process during bone tissue engineering. The ability to deliver small biomolecules, such as dexamethasone, different growth factors, vitamins and mineral ions depends on the morphology, porosity, and crystallinity of SNMs and their composites with other polymeric materials. In this review, the abilities of SNMs to perform as suitable scaffolds for bone tissue engineering are comprehensively discussed.

The effect of Yarrowia lipolytical-asparaginase on apoptosis induction and inhibition of growth in Burkitt's lymphoma Raji and acute lymphoblastic leukemia MOLT-4 cells.

l-Asparaginase (l-asparagine amidohydrolase; E.C.3.5.1.1) as an anticancer agent is used to treat acute lymphocytic leukemia (ALL), Human Burkitt's lymphoma and non-Hodgkin's lymphoma. The commercial asparaginases are obtained from bacteria Erwinia chrysanthemi and Escherichia coli now which had many side effects. In this study, the effects of a novel l-asparaginase from yeast Yarrowia lipolytica was investigated on human ALL and Burkitt's lymphoma cell lines. The l-asparaginase causes metabolic stress, cytotoxicity, and apoptosis due to the arrest of the G0 cell cycle, the activation of caspase-3 and the modulation of mitochondrial membrane integrity. The RT-PCR analysis showed a significant increase in the pro-apoptosis genes such as Bax, Caspase-3, Caspase-8, Caspase-9 and p53 (P < 0.05) while the anti-apoptotic marker Bcl-2 was significantly decreased (P < 0.05). Furthermore, Y. lipolytical-asparaginase causes autophagy and increased ROS. The l-asparaginase has cytotoxic and anticancer effects higher than commercial asparaginase. In conclusion, Y. lipolytical-asparaginase shows interesting anticancer activity and it can be introduced as a new eukaryotic and therapeutic agent and strategy for ALL and Burkitt's lymphoma treatment after the in vivo and clinical experiments.

MicroRNA-193a and taxol combination: A new strategy for treatment of colorectal cancer.

Micro RNAs (miRNAs) show a considerable promise as a therapeutic agent for combination therapy of colorectal cancer (CRC). Given that, the current study was purposed to explore the potential therapeutic role and underlying mechanism of miR-193a as a promising tumor suppressor in human CRC cell lines in combination with Taxol. Therefore, HT-29 cells with the lowest expression levels of miR-193a were treated with miR-193a mimics and Taxol, separately or in combination. Functional analyses showed that the combination therapy inhibited migration and colony formation of HT-29 cells and arrested the cell cycle at the G1 phase. Moreover, treatment with Taxol reduced cell survival with an increase in mRNA expression of metastasis-related genes caspase-3 and caspase-9, whereas miR-193a transfection alone didn't significantly influence cell viability and apoptosis induction. Quantitative reverse transcription polymerase chain reaction results also revealed that miR-193a replacement decreased the expression levels of c-Myc, MMP-9, vimentin, and ROCK in treatment groups compared to the controls. Therefore, it could be concluded miR-193a inactivates cell migration via suppression of metastasis pathways in CRC and through downregulation of c-Myc, acts as a negative regulator of cell cycle and growth. Then, our findings imply that miR-193a replacement combined with Taxol chemotherapy could be considered as a new potential therapeutic approach for improvement of CRC treatment.

Comparison of DNA and mRNA vaccines against cancer.

Nucleic acid vaccines (NAVs) have recently been tested as a cancer therapy. DNA and mRNA vaccines deliver genetic information encoding tumor antigens (TAs) to the host, which then produces immune responses against cancer cells that express the TAs. Although NAVs are easy, safe, and simple to manufacture, they have not so far been considered viable alternatives to peptide vaccines. Choosing the right TAs, insufficient immunogenicity, and the immunosuppressive nature of cancer are some challenges to this approach. In this review, we discuss approaches that been used to improve the efficiency of anticancer NAVs.

Recent advances on HIV DNA vaccines development: Stepwise improvements to clinical trials.

According to WHO (World Health Organization) reports, more than 770,000 people died from HIV and almost 1.7 million people becoming newly infected in the worldwide in 2018. Therefore, many attempts should be done to produce a forceful vaccine to control the AIDS. DNA-based vaccines have been investigated for HIV vaccination by researches during the recent 20 years. The DNA vaccines are novel approach for induction of both type of immune responses (cellular and humoral) in the host cells and have many advantages including high stability, fast and easy of fabrication and absence of severe side effects when compared with other vaccination methods. Recent studies have been focused on vaccine design, immune responses and on the use of adjuvants as a promising strategy for increased level of responses, delivery approaches by viral and non-viral methods and vector design for different antigens of HIV virus. In this review, we outlined the aforementioned advances on HIV DNA vaccines. Then we described the future trends in clinical trials as a strong strategy even in healthy volunteers and the potential developments in control and prevention of HIV.

Applications of Spherical Nucleic Acid Nanoparticles as Delivery Systems.

Spherical nucleic acids (SNAs) are nanostructures consisting of highly oriented, dense layers of oligonucleotides arranged in a spherical 3D geometry. Owing to their unique properties and function, SNAs occupy a material space distinct from 'DNA nanotechnology' and DNA origami. Over the past two decades SNAs have revolutionized gene regulation, drug delivery, gene therapy, and molecular diagnostics, and show promise for both antisense and RNAi therapy. We focus here on recent advances in the synthesis and application of SNAs in gene and drug delivery, diagnostics, and immunomodulation, as well as on the utility of nanoflares as intracellular mRNA detection systems.

Recent advances on thermosensitive and pH-sensitive liposomes employed in controlled release.

Nanotechnology has recently gained lots of interest in drug delivery due to its potential to improve the therapeutic outcomes of various diseases. Particularly, a wide range of different nano-sized vesicles has been investigated for drug delivery. Among them, one of the most attractive and well-investigated nanocarriers are liposomes. Although liposomes have several advantages such as low toxicity, biodegradability and biocompatibility as well as accumulate in tumor site via enhanced permeability and retention (EPR) effect, inefficient drug delivery to the target cells could affect the therapeutic purpose of most of conventional liposomal formulations. Therefore, new systems of drug release including stimuli-responsive liposomal have been introduced for the improvement of the efficacy and release payloads in a site-specific manner. Stimuli-responsive liposomes stay stable in blood stream circulation but are activated in response to internal or external stimuli. This review highlights the development of thermosensitive and pH-sensitive liposomes, focusing on liposomal compositions and the effects of the synthetic polymers on their drug release behavior. Furthermore, in vitro and in vivo applications of these formulations will be discussed.

Aptasensors as a new sensing technology developed for the detection of MUC1 mucin: A review.

Mucin 1 protein (MUC1) is a membrane-associated glycoprotein overexpressed in the majority of human malignancies and considered as a predominant protein biomarker in cancers. Owing to the crucial role of MUC1 in cancer dissemination and metastasis, detection and quantification of this biomarker is of great importance in clinical diagnostics. Today, there exist a wide variety of strategies for the determination of various types of disease biomarkers, especially MUC1. In this regard, aptamers, as artificial single-stranded DNA or RNA oligonucleotides with catalytic and receptor properties, have drawn lots of attention for the development of biosensing platforms. So far, various sensitivity-enhancement techniques in combination with a broad range of smart nanomaterials have integrated into the design of novel aptamer-based biosensors (aptasensors) to improve detection limit and sensitivity of analyte determination. 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 MUC1 based on optical and electrochemical platforms.

Correction to: Curcumin in Advancing Treatment for Gynecological Cancers with Developed Drug- and Radiotherapy-Associated Resistance.

The affiliation of the 6th author Dr. Abolfazl Mehdizadehkashi was incorrect. It has been corrected to Endometriosis Research Center, Iran University of Medical Sciences, Tehran, Iran.