Fluorescence anisotropy cytosensing of folate receptor positive tumor cells using 3D polyurethane-GO-foams modified with folic acid: molecular dynamics and in vitro studies.

Integrated polyurethane (PU)-based foams modified with PEGylated graphene oxide and folic acid (PU@GO-PEG-FA) were developed with the goal of capturing and detecting tumor cells with precision. The detection of the modified PU@GO-PEG surface through FA against folate receptor-overexpressed tumor cells is the basis for tumor cell capture. Molecular dynamics (MD) simulations were applied to study the strength of FA interactions with the folate receptor. Based on the obtained results, the folate receptor has intense interactions with FA, which leads to the reduction in the FA interactions with PEG, and so decreases the fluorescence intensity of the biosensor. The synergistic interactions offer the FA-modified foams a high efficiency for capturing the tumor cell. Using a turn-off fluorescence technique based on the complicated interaction of FA-folate receptor generated by target recognition, the enhanced capture tumor cells could be directly read out at excitation-emission wavelengths of 380-450 nm. The working range is between 1×10 2 to 2×10 4 cells mL -1 with a detection limit of 25 cells mL -1 and good reproducibility with relative standard deviation of 2.35%. Overall, findings demonstrate that the fluorescence-based biosensor has a significant advantage for early tumor cell diagnosis.

Organoid technology: Current standing and future perspectives.

Organoids are powerful systems to facilitate the study of individuals' disorders and personalized treatments. This emerging technology has improved the chance of translatability of drugs for preclinical therapies and mimicking of the complexity of organs, proposing numerous approaches for human disease modeling, tissue engineering, drug development, diagnosis, and regenerative medicine. In this review, we outline the history of organoid technology and summarize its faithful applications, and then we discuss the challenges and limitations encountered by three-dimensional organoids. Finally, we propose that human organoids offer a basic mechanistic infrastructure for "human modeling" systems to prescribe personalized medicines.

Hierarchical multifunctional graphene oxide cancer nanotheranostics agent for synchronous switchable fluorescence imaging and chemical therapy.

A nanotheranostics platform was synthesized based on PEGylated graphene oxide-gold nanoparticles and specified with aptamer toward the MUC-1-positive tumor cells. Subsequently, it was loaded with doxorubicin, used for non-invasive fluorescence imaging and therapy of breast and colon tumors. The success of the nano-coating at each synthesis step was characterized through FTIR, XRD, TGA, FE-SEM, EDAX, Zeta-potential, and fluorescence spectroscopy. Besides, the ability of the designed platform in targeted imaging, drug delivery, and in vitro therapy were evaluated using fluorescence microscopy and flow cytometry. The selected aptamer acts as a quencher, resulting in an "on/off" fluorescence biosensor. When the aptamer specifically binds to the MUC-1 receptor, its double strands separate, leading to the drug release and the recovery of the fluorescence of ("On" state) at the excitation wavelength of 300 nm. Based on cell toxicity results, this platform has more toxicity toward the MUC-1-positive tumor cells (HT-29 and MCF-7) compared  to MUC-1-negative cells (Hep-G2), representing its selective performance. Thus, this nano-platform can be introduced as a multifunctional cancer nanotheranostics system for tracing particular biomarkers, non-invasive imaging, and targeted chemotherapy. Graphical abstract.

Smart co-delivery of plasmid DNA and doxorubicin using MCM-chitosan-PEG polymerization functionalized with MUC-1 aptamer against breast cancer.

This study introduces an innovative co-delivery approach using the MCM-co-polymerized nanosystem, integrating chitosan and polyethylene glycol, and targeted by the MUC-1 aptamer (MCM@CS@PEG-APT). This system enables simultaneous delivery of the GFP plasmid and doxorubicin (DOX). The synthesis of the nanosystem was thoroughly characterized at each step, including FTIR, XRD, BET, DLS, FE-SEM, and HRTEM analyses. The impact of individual polymers (chitosan and PEG) on payload retardation was compared to the co-polymerized MCM@CS@PEG conjugation. Furthermore, the DOX release mechanism was investigated using various kinetic models. The nanosystem's potential for delivering GFP plasmid and DOX separately and simultaneously was assessed through fluorescence microscopy and flow cytometry. The co-polymerized nanosystem exhibited superior payload entrapment (1:100 ratio of Plasmid:NPs) compared to separately polymer-coated counterparts (1:640 ratio of Plasmid:NPs). Besides, the presence of pH-sensitive chitosan creates a smart nanosystem for efficient DOX and GFP plasmid delivery into tumor cells, along with a Higuchi model pattern for drug release. Toxicity assessments against breast tumor cells also indicated reduced off-target effects compared to pure DOX, introducing it as a promising candidate for targeted cancer therapy. Cellular uptake findings demonstrated the nanosystem's ability to deliver GFP plasmid and DOX separately into MCF-7 cells, with rates of 32% and 98%, respectively. Flow cytometry results confirmed efficient co-delivery, with 42.7% of cells showing the presence of both GFP-plasmid and DOX, while 52.2% exclusively contained DOX. Overall, our study explores the co-delivery potential of the MCM@CS@PEG-APT nanosystem in breast cancer therapy. This system's ability to co-deliver multiple agents preciselyopens new avenues for targeted therapeutic strategies.

Investigation of physical, mechanical and biological properties of polyhydroxybutyrate-chitosan/graphene oxide nanocomposite scaffolds for bone tissue engineering applications.

Mechanical properties appropriate to native tissues, as an essential component in bone tissue engineering scaffolds, plays a significant role in tissue formation. In the current study, Poly-3 hydroxybutyrate-chitosan (PC) scaffolds reinforced with graphene oxide (GO) were made by the electrospinning method. The addition of GO led to a decrease in fibers diameter, an increase in thermal capacity and an improvement in the surface hydrophilicity of nanocomposite scaffolds. A significant increase in the mechanical properties of PC/GO (PCG) nanocomposite scaffolds was achieved due to the inherent strength of GO as well as its uniform dispersion throughout the polymeric matrix owing to hydrogen bonding and polar interactions. Also, lower biological degradation of the scaffolds (~30% in 100 days) due to the presence of GO provides essential mechanical support for bone regeneration. In addition, the bioactivity results showed that GO reinforcement significantly increases the biomineralization on the surface of the scaffolds. Evaluating cell adhesion and proliferation, as well as ALP activity of MG-63 cells on PC and PCG scaffolds indicated the positive effect of GO on scaffolds' biocompatibility. Overall, the improvement of physicochemical, mechanical, and biological properties of GO-reinforced scaffolds shows the potential of PCG nanocomposite scaffolds for bone tissue engineering.

Smartphone-assisted lab-in-a-tube device using gold nanocluster-based aptasensor for detection of MUC1-overexpressed tumor cells.

Developing smartphone technology for point-of-care diagnosis is one of the current favorable trends in the field of biosensors. In fact, using smartphones can provide better accessibility and facility for rapid diagnosis of diseases. On the other hand, the detection of circulating tumor cells (CTCs) is one of the recent methods for the early diagnosis of cancer. Here, a new smartphone-assisted lab-in-a-tube device is introduced for the detection of Mucin 1 (MUC1) overexpressed tumor-derived cell lines using gold nanoclusters (GNCs)-based aptasensor. Accordingly, commercial polyurethane (PU) foam was first coated with graphene oxide (GO) to increase its surface area (8.45-fold), and improve its wettability. The surface of the resulting three-dimensional PU-GO (3DPU-GO) platform was then modified by MUC1 aptamer-GNCs to provide the required sensitivity and specificity through a turn "on/off" detection system. The proposed biosensor was first optimized with a spectrophotometer method. Afterward, findings were evaluated based on the red color intensity of the lab-in-a-tube system; and indicated the high ability of the biosensor for detection of MUC1-overexpressed tumor cell lines in the range of 250-20,000 cells mL-1 with a limit of detection of 221 cells mL-1. In addition, the developed biosensor showed a decent selectivity against positive-control cell lines (MCF-7, and HT-29) in comparison to negative-control cell lines (HEK293, and L929). Notably, the results represented good accordance with reference methods including spectroscopy devices. Ultimately, the results of this work bring a new perspective to the field of point-of-care detection and can be considered in future biosensors.

Penicillin and Oxacillin Loaded on PEGylated-Graphene Oxide to Enhance the Activity of the Antibiotics against Methicillin-Resistant Staphylococcus aureus.

Infectious diseases are known as the second biggest cause of death worldwide, due to the development of antibiotic resistance. To overcome this problem, nanotechnology offers some promising approaches, such as drug delivery systems that can enhance drug efficiency. Herein, a Graphene Oxide-polyethylene glycol (GO-PEG) nano-platform was synthesized and penicillin and oxacillin, two antibiotics that are ineffective against Methicillin-resistant S. aureus (MRSA), were loaded on it to improve their effectiveness. The nanocomposites were characterized using FTIR, XRD, UV-Vis, FE-SEM/EDX, and Zeta potential analyses, followed by an evaluation of their antibacterial activity toward MRSA. Based on the results, drug loaded GO-PEG nanocomposites with loading efficiencies of 81% and 92% for penicillin and oxacillin, respectively, were successfully synthesized. They showed a controlled release within six days. The zeta potential of GO-PEG-oxacillin and penicillin was -13 mV and -11 mV, respectively. The composites showed much more activity against MRSA (80-85% inhibition) in comparison to GO-PEG (almost 0% inhibition) and pure antibiotics (40-45% inhibition). SEM images of MRSA treated with GO-PEG-antibiotics showed a deformation in the structure of bacterial cells, which led to the collapse of their intracellular components. These results demonstrate the effectiveness of utilizing the GO-based nanoplatforms in enhancing the antibacterial activity of the antibiotics.

Graphene oxide quantum dot-chitosan nanotheranostic platform as a pH-responsive carrier for improving curcumin uptake internalization: In vitro & in silico study.

We herein fabricated a cancer nanotheranostics platform based on Graphene Oxide Quantum Dot-Chitosan-polyethylene glycol nanoconjugate (GOQD-CS-PEG), which were targeted with MUC-1 aptamer towards breast and colon tumors. The interaction between aptamer and MUC-1 receptor on the desired cells was investigated utilizing molecular docking. The process of curcumin release was investigated, as well as the potential of the produced nanocomposite in targeted drug delivery, specific detection, and photoluminescence imaging. The fluorescence intensity of GOQD-CS-PEG was reduced due to transferred energy between (cytosine-guanin) base pairs in the hairpin structure of the aptamer, resulting in an "on/off" photoluminescence bio-sensing. Interestingly, the integration of pH-responsive chitosan nanoparticles in the nanocomposite results in a smart nanocomposite capable of delivering more curcumin to desired tumor cells. When selectively binds to the MUC-1 receptor, the two strands of aptamer separate in acidic conditions, resulting in a sustained drug release and photoluminescence recovery. The cytotoxicity results also revealed that the nanocomposite was more toxic to MUC-1-overexpressed tumor cells than to negative control cell lines, confirming its selective targeting. As a result, the proposed nanocomposite could be used as an intelligent cancer nanotheranostic platform for tracing MUC-1-overexpressed tumor cells and targeting them with great efficiency and selectivity.

Targeting autophagy, oxidative stress, and ER stress for neurodegenerative disease treatment.

Protein homeostasis is a vital process for cell function and, therefore, disruption of the molecular mechanisms involved in this process, such as autophagy, may contribute to neurodegenerative diseases (NDs). Apart from autophagy disruption, excess oxidative stress and endoplasmic reticulum (ER) stress are additional main molecular mechanisms underlying neurodegeneration, leading to protein aggregation, and mitochondrial dysfunction. Notably, these primary molecular processes are interconnected pathways, which have synergistic effects on each other. Therefore, we propose that targeting of the crosstalk between autophagy, oxidative stress and ER stress simultaneously may play a critical role in healing NDs. NeuroNanoTechnology, as a revolutionized approach, in combination with an in-silico strategy, holds great promise for developing de-novo structures for targeting and modulating neuro-molecular pathways. Accordingly, this review outlines the contributions of autophagy, oxidative stress, and ER stress in neurodegenerative conditions along with a particular focus on the crosstalk among these pathways. Furthermore, we provide a comprehensive discussion on the potential of nanomaterials to target this crosstalk and suggest this potential as a promising opportunity in neuroprotection.

Mesoporous silica@chitosan@gold nanoparticles as "on/off" optical biosensor and pH-sensitive theranostic platform against cancer.

A cancer nanotheranostic system was fabricated based on mesoporous silica@chitosan@gold (MCM@CS@Au) nanosystem targeted by aptamer toward the MUC-1 positive tumor cells. Subsequently, curcumin as an efficient herbal anticancer drug was first encapsulated into chitosan-triphosphate nanoparticles and then the resulted nanoparticle was loaded into the nanosystem (MCM@CS@Au-Apt). The nanosystem successful fabrication was approved at each synthesis step through FTIR, XRD, BET, DLS, FE-SEM, HRTEM, and fluorescence spectroscopy. Besides, the interaction between aptamer and curcumin was evaluated using full atomistic molecular dynamics simulations. The mechanism of curcumin release was likewise investigated through different kinetic models. Afterwards, the potential of the designed nanosystem in targeted imaging, and drug delivery was evaluated using fluorescence microscopy and flow cytometry. It was found that the energy transfer between the base pairs in the hairpin of double strands of DNA aptamer acts as a quencher for MCM@CS@Au fluorescence culminating in an "on/off" optical biosensor. On the other hand, the presence of pH-sensitive chitosan nanoparticles creates smart nanosystem to deliver more curcumin into the desired cells. Indeed, when the aptamer specifically binds to the MUC-1 receptor, its double strands separate under the low pH condition, leading to the drug release and the recovery of the fluorescence ("On" state). Based on the toxicity results, this nanosystem had more toxicity toward the MUC-1-positive tumor cells than MUC-1-negative cells, representing its selective targeting. Therefore, this nanosystem could be introduced as a smart anticancer nanotheranostic system for tracing particular biomarkers (MUC-1), non-invasive fluorescence imaging, and targeted curcumin delivery.

Gene Editing-Based Technologies for Beta-hemoglobinopathies Treatment.

Beta (ß)-thalassemia is a group of human inherited abnormalities caused by various molecular defects, which involves a decrease or cessation in the balanced synthesis of the ß-globin chains in hemoglobin structure. Traditional treatment for ß-thalassemia major is allogeneic bone marrow transplantation (BMT) from a completely matched donor. The limited number of human leukocyte antigen (HLA)-matched donors, long-term use of immunosuppressive regimen and higher risk of immunological complications have limited the application of this therapeutic approach. Furthermore, despite improvements in transfusion practices and chelation treatment, many lingering challenges have encouraged researchers to develop newer therapeutic strategies such as nanomedicine and gene editing. One of the most powerful arms of genetic manipulation is gene editing tools, including transcription activator-like effector nucleases, zinc-finger nucleases, and clustered regularly interspaced short palindromic repeat-Cas-associated nucleases. These tools have concentrated on γ- or ß-globin addition, regulating the transcription factors involved in expression of endogenous γ-globin such as KLF1, silencing of γ-globin inhibitors including BCL11A, SOX6, and LRF/ZBTB7A, and gene repair strategies. In this review article, we present a systematic overview of the appliances of gene editing tools for ß-thalassemia treatment and paving the way for patients' therapy.

Nanobased Platforms for Diagnosis and Treatment of COVID-19: From Benchtop to Bedside.

Human respiratory viral infections are the leading cause of morbidity and mortality around the world. Among the various respiratory viruses, coronaviruses (e.g., SARS-CoV-2) have created the greatest challenge and most frightening health threat worldwide. Human coronaviruses typically infect the upper respiratory tract, causing illnesses that range from common cold-like symptoms to severe acute respiratory infections. Several promising vaccine formulations have become available since the beginning of 2021. Nevertheless, achievement of herd immunity is still far from being realized. Social distancing remains the only effective measure against SARS-CoV-2 infection. Nanobiotechnology enables the design of nanobiosensors. These nanomedical diagnostic devices have opened new vistas for early detection of viral infections. The present review outlines recent research on the effectiveness of nanoplatforms as diagnostic and antiviral tools against coronaviruses. The biological properties of coronavirus and infected host organs are discussed. The challenges and limitations encountered in combating SARS-CoV-2 are highlighted. Potential nanodevices such as nanosensors, nanobased vaccines, and smart nanomedicines are subsequently presented for combating current and future mutated versions of coronaviruses.

Graphene oxide and its derivatives as promising In-vitro bio-imaging platforms.

Intrinsic fluorescence and versatile optical properties of Graphene Oxide (GO) in visible and near-infrared range introduce this nanomaterial as a promising candidate for numerous clinical applications for early-diagnose of diseases. Despite recent progresses in the impact of major features of GO on the photoluminescence properties of GO, their modifications have not yet systematically understood. Here, to study the modification effects on the fluorescence behavior, poly ethylene glycol (PEG) polymer, metal nanoparticles (Au and Fe3O4) and folic acid (FA) molecules were used to functionalize the GO surface. The fluorescence performances in different environments (water, DMEM cell media and phosphate buffer with two different pH values) were assessed through fluorescence spectroscopy and fluorescent microscopy, while Fourier-transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD) and Scanning electron microscopy (SEM) were utilized to evaluate the modifications of chemical structures. The modification of GO with desired molecules improved the photoluminescence property. The synthesized platforms of GO-PEG, GO-PEG-Au, GO-PEG-Fe3O4 and GO-PEG-FA illustrated emissions in three main fluorescence regions (blue, green and red), suitable for tracing and bio-imaging purposes. Considering MTT results, these platforms potentially positioned themselves as non-invasive optical sensors for the diagnosis alternatives of traditional imaging agents.

Altmetric Analysis of Contemporary Iranian Medical Journals.

BACKGROUND: Altmetrics is a newly emerging scholarly tool measuring online attention surrounding scientific research outputs. With respect to increasing demand of disseminating research findings on the World Wide Web, this study aims to analyze the altmetric statues of Iranian medical journals. METHODS: On February 27, 2019, the list of Iranian medical journals extracted from http://journals.research.ac.ir/ and consequently altmetric data token out from Altmetric database (Altmetric LLP, London, UK). The science mapping done via keyword co-occurrence, co-citation and co-authorship, network analysis using the VOSviewer. The Pearson coefficient was then employed for the correlation analysis using R. RESULTS: Among a total of 104 journals, 7518 articles were mentioned in Altmetric data resources (Mean: 72.28, Confidence Level (95.0%): 16.8), total mentions were 27577 (Mean: 265.16, Confidence Level (95.0%): 79.9). Considering the total mentions of articles, International Journal of Preventive Medicine achieved the first rank, followed by Journal of Research in Medical Sciences and Iranian Journal of Public Health. Notably, Twitter was the most popular altmetric resource followed by Facebook and news outlets. Tweets were generally from the United States and United Kingdom. Among top 5% popular Iranian medical articles multiple sclerosis, cancer, and anxiety was hot topics. CONCLUSIONS: Iranian biomedical journal editors and research scientists needs to be more dynamic in World Wide Web using social media, post-publication peer review tools, Stack Exchange (Q and A) sites, research highlight tools, Wikipedia, and etc. In spite, more attention to the concept of evidence-based policymaking, by Iranian government along with the health policymakers seems necessary.

An Improved Method for Fabrication of Ag-GO Nanocomposite with Controlled Anti-Cancer and Anti-bacterial Behavior; A Comparative Study.

In this study, two green procedures for Silver-Graphene Oxide (Ag-GO) nanocomposite synthesis were investigated. As a common method, AgNO3 was first loaded on the GO surface and then was reduced and stabilized by walnut green husk extract, producing Ag-GO-І. As an innovative approach, GO was first exposed to the extract and then the AgNO3 was added as the second step, producing Ag-GO-П. Physicochemical properties, antibacterial and cytotoxicity activity of both nanocomposites were subsequently studied comparing with free silver nanoparticles (AgNPs) and pure GO. Based on the results, exposure of GO to the extract, as a reducing agent, at the first/last step of the synthesis process resulted in the fundamental differences in the final products. So that, high amounts of agglomerated silver nanoparticles were formed between the GO sheets, when using the common method, whereas in Ag-GO-П, small AgNPs were formed on the GO sheets without aggregation, entirely covering the sheets. Antibacterial and cytotoxic behavior of these nanomaterials could be compared as AgNPs > Ag-GO-П > Ag-GO-І. It is assumed that these differences are due to control of unwanted nucleation in the synthesis process that Ag nanoparticles are smaller with less agglomeration when the GO surfaces are pre-treated with reducing agent.

Targeted Graphene Oxide Networks: Cytotoxicity and Synergy with Anticancer Agents.

An effective strategy to inhibit endocytosis in cancer cells is presented where modified net-type graphene oxide (GO) sheets, bound with multiple cell surface receptors, are introduced and synthesized as novel anticancer agents. The results suggest that the binding connects GO sheets with neighboring lipid rafts, neutralizes endocytosis, and causes metabolic deprivation. As a result, tumor cell survival and proliferation are reduced. Live cell confocal microscopy imaging reveals that GO-PEGFA (folate-PEGylated GO) (PEG, polyethylene glycol) is internalized by tumor cells, while GO-PEGRGD (tripeptide Arg-Gly-Asp PEGylated GO) associates with the external cell membrane (not internalized). In vitro exposure of tumor cells to GO-PEGFA or GO-PEGRGD reduces the cell viability by 35%, compared to 50% reduction using methotrexate (100 µM). The combination of modified GO sheets with methotrexate or doxorubicin shows a greater toxicity (80% reduction in cell viability) than the individual agents. The proposed setup demonstrates a significant synergy in limiting tumor cell growth.

Reconstituted Keratin Biomaterial with Enhanced Ductility.

Nowadays the waste from protein fibres represents an important renewable source for a new generation of biomaterials and promising competitors for carbohydrate based biomaterials. Regenerated keratin biomaterials are biodegradable in vivo and in vitro, biocompatible, and support cell attachment and proliferation; however, their major drawback has been their weak mechanical properties such as ductility. The following study was conducted in an attempt to improve the ductility of reconstituted keratin films obtained from Australian merino wool fibres. Keratin was extracted from wool fibres according to an established protocol proposed by Yamauchi, and then dialyzed and desalted by multiple diafiltration wash cycles. The resulting keratin film was transparent, biodegradable, and, opposite to its predecessors, mechanically durable, possessing a Young modulus about 12.5 MPa with 35% extensibility. The polypeptide chains were found to rearrange themselves in the ß-sheet state in this keratin film, which was shown to be semi-crystalline. This film, unlike its predecessors, did not support human cell proliferation. These properties of the diafiltered keratin film have led us to think that diafiltration resulted in producing a totally new keratin film, which is envisaged to find applications in various areas.

Expression and Purification of Functionally Active Recombinant Human Alpha 1-Antitrypsin in Methylotrophic Yeast Pichia pastoris.

Human alpha 1-antitrypsin (AAT) cDNA was obtained from HepG2 cell lines. After PCR and construction of expression vector pPICZα-AAT, human AAT was expressed in the yeast Pichia pastoris (P.pastoris) in a secretary manner and under the control of inducible alcohol oxidase 1 (AOX1) promoter. The amount of AAT protein in medium was measured as 60 mg/l 72 hr after induction with methanol. Results indicated the presence of protease inhibitory function of the protein against elastase. Purification was done using His-tag affinity chromatography. Due to the different patterns of glycosylation in yeast and human, the recombinant AAT showed different SDS-PAGE patterns compared to that of serum-derived AAT while pI shifted from 4.9 in native AAT compared to 5.2 in recombinant AAT constructed in this study.