BioMedical Visualization Association (BMVA)

Gene therapy using clustered regularly interspaced short palindromic repeat plasmids (pCRISPR) reduces mistakes in gene editing and prevents engendering integrational mutagenesis that has been seen in available genome engineering technologies. Developing an ideal and traceable nanocarrier, which can accurately and efficiently transfer this complex into the cytosol and which facilitates the journey towards the nucleus, is a fascinating area of research. Polyethylenimine (PEI) functionalized carbon dots (CD-PEI) were fabricated by one-step microwave assisted pyrolysis with an average size around 3 nm. This CD-PEI showed good potential for intracellular delivery of genetic materials (~70%). Also, this CD-PEI with passive surface modification with low molecular PEI (2 kDa) has a very high quantum yield, as high as 40% with low cytotoxicity. The expression rate of the pCRISPR was around 15% in the HEK-293 cell which is comparable with the pristine PEI. Furthermore, the CD-PEI demonstrated good properties, such as high quantum yield, biocompatibility and tunable emission wavelengths, suggesting the potential application of photoluminescent functionalized CDs as a suitable, traceable nanocarrier for CRISPR delivery.

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Regenerating chondral and osteochondral injuries is a main challenge in orthopedics. Some therapeutic strategies such as joint preservation operations, non-operative management, palliative surgery, and arthroplasty are the common clinical methods for repairing the cartilage defects. These treatments show often satisfactory as short-term outcomes and without clear long-term prospects. Over the past decade, the development of tissue engineering technologies offer a new therapeutic option to treat patients suffering from chondral lesions. Silk fibroin is a potent and advanced biomaterial for regenerating both soft and hard tissues. Fibroin scaffolds possess superior mechanical strength, suitable bioactivity, elasticity, degradability, and tailorable chemical structure. Due to the important properties as natural biomaterials, the fabrications of various types of scaffolds/matrices for regenerating the tissues like cartilage for regeneration and repairing the defects are possible. This review highlights the investigations on silk-based biomaterials for cartilage tissue engineering. The possibilities for future clinical application of silk fibroin based constructs in repairing intervertebral disk, anterior cruciate ligament, meniscus, and osteochondral defects are evaluated in detail.

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Breast and prostate cancers are common types of cancers with various strategies, such as chemotherapy and radiotherapy, for their therapy. Since these methods have undesired side effects and poor target affinity, neoteric strategies—known as aptamer-based smart drug delivery systems (SDDSs)—have been developed in recent years to overcome the obstacles of current treatment, and investigated for a clinical trial. The high affinity and versatility of aptamers for binding to the corresponding targets make them highly noticeable agents in the drug delivery domains. In addition to their exceptional benefits, aptamers are able to overcome tumor resistance because of their high selectivity and low toxicity. Furthermore, aptamers can conjugate with various drugs, nanoparticles and antibodies and effectively deliver them to the specific breast and prostate cells. This review highlights the current researches in aptamer-conjugate developments for targeting breast and prostate cancers, with the special focus on the nanoparticle-aptamer bioconjugates, systematic evolution of ligands by exponential enrichment (SELEX) system and SDDS, especially cutting-edge articles from 2008 to present. Finally, the future prospects and challenges are described.

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Recently, nanocomposite nanofibers have been extensively used for biomedical applications. It is expected that simultaneous incorporation of antibiotic drugs and ZnO nanoparticles into nanofiber resulted in providing the synergistic anti-bacterial effect. The main aim of the present study is to fabricate polyvinyl alcohol (PVA)/carboxymethyl cellulose (CMC)-ZnO nanocomposite fibrous mats containing erythromycin (EM) drug and crosslink them using 2% glutaraldehyde vapor and 3% AlCl3 alcoholic solution. The fabricated nanofibers characterized via TGA, FTIR, TEM, and SEM, indicating that the addition of ZnO nanoparticles and EM molecules into the fabricated nanofibers resulted in changing their average diameter. Their anti-bacterial activity was studied against S. aureus and E. coli and found that PVA-CMC/ZnO-EM nanofibers show excellent antimicrobial activity. In-vitro release profile showed that EM release from PVA-CMC/ZnO-EM nanofibers was slowly increased. Sustained drug release profile and excellent anti-bacterial activity of PVA-CMC/ZnO-EM nanofiber indicated that it was an ideal biomaterial for wound dressings.

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Liposomes, lipid-based vesicular systems, have attracted major interest as a means to improve drug delivery to various organs and tissues in the human body. Recent literature highlights the benefits of liposomes for use as drug delivery systems, including encapsulating of both hydrophobic and hydrophilic cargos, passive and active targeting, enhanced drug bioavailability and therapeutic effects, reduced systemic side effects, improved cargo penetration into the target tissue and triggered contents release. Pioneering work of liposomes researchers led to introduction of long-circulating, ligand-targeted and triggered release liposomes, as well as, liposomes containing nucleic acids and vesicles containing combination of cargos. Altogether, these findings have led to widespread application of liposomes in a plethora of areas from cancer to conditions such as cardiovascular, neurologic, respiratory, skin, autoimmune and eye disorders. There are numerous review articles on the application of liposomes in treatment of cancer, which seems the primary focus, whereas other diseases also benefit from liposome-mediated treatments. Therefore, this article provides an illustrated detailed overview of liposomal formulations, in vitro characterization and their applications in different disorders other than cancer. Challenges and future directions, which must be considered to obtain the most benefit from applications of liposomes in these disorders, are discussed.

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Cardiovascular diseases are the number one cause of heart failure and death in the world, and the transplantation of the heart is an effective and viable choice for treatment despite presenting many disadvantages (most notably, transplant heart availability). To overcome this problem, cardiac tissue engineering is considered a promising approach by using implantable artificial blood vessels, injectable gels, and cardiac patches (to name a few) made from biodegradable polymers. Biodegradable polymers are classified into two main categories: natural and synthetic polymers. Natural biodegradable polymers have some distinct advantages such as biodegradability, abundant availability, and renewability but have some significant drawbacks such as rapid degradation, insufficient electrical conductivity, immunological reaction, and poor mechanical properties for cardiac tissue engineering. Synthetic biodegradable polymers have some advantages such as strong mechanical properties, controlled structure, great processing flexibility, and usually no immunological concerns; however, they have some drawbacks such as a lack of cell attachment and possible low biocompatibility. Some applications have combined the best of both and exciting new natural/synthetic composites have been utilized. Recently, the use of nanostructured polymers and polymer nanocomposites has revolutionized the field of cardiac tissue engineering due to their enhanced mechanical, electrical, and surface properties promoting tissue growth. In this review, recent research on the use of biodegradable natural/synthetic nanocomposite polymers in cardiac tissue engineering is presented with forward looking thoughts provided for what is needed for the field to mature.

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With continual rapid developments in the biomedical field and understanding of the important mechanisms and pharmacokinetics of biological molecules, controlled drug delivery systems (CDDSs) have been at the forefront over conventional drug delivery systems. Over the past several years, scientists have placed boundless energy and time into exploiting a wide variety of excipients, particularly diverse polymers, both natural and synthetic. More recently, the development of nano polymer blends has achieved noteworthy attention due to their amazing properties, such as biocompatibility, biodegradability and more importantly, their pivotal role in controlled and sustained drug release in vitro and in vivo. These compounds come with a number of effective benefits for improving problems of targeted or controlled drug and gene delivery systems; thus, they have been extensively used in medical and pharmaceutical applications. Additionally, they are quite attractive for wound dressings, textiles, tissue engineering, and biomedical prostheses. In this sense, some important and workable natural polymers (namely, chitosan (CS), starch and cellulose) and some applicable synthetic ones (such as poly-lactic-co-glycolic acid (PLGA), poly(lactic acid) (PLA) and poly-glycolic acid (PGA)) have played an indispensable role over the last two decades for their therapeutic effects owing to their appealing and renewable biological properties. According to our data, this is the first review article highlighting CDDSs composed of diverse natural and synthetic nano biopolymers, blended for biological purposes, mostly over the past five years; other reviews have just briefly mentioned the use of such blended polymers. We, additionally, try to make comparisons between various nano blending systems in terms of improved sustained and controlled drug release behavior.

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This study, for the first time, reports the synthesis of CuO- and Cu2O nanoparticles (NPs) using the Salvia hispanica extract by a high-gravity technique. The original green synthesis procedure led to the formation of nanoparticles with promising catalytic and biological properties. The synthesized nanoparticles were fully characterized and their catalytic activity was evaluated through a typical Azide-Alkyne Cycloaddition (AAC) reaction. The potential antibacterial activity against gram positive (S. aureus) and gram negative (E. coli) bacteria were investigated. It was shown that the antibacterial properties were independent of the NP morphology as well as of the texture of the synthesis media. As a result, the presently synthesized nanoparticles showed very good photocatalytic and catalytic activities in comparison with the literature. From a biological perspective, they showed lower cytotoxicity in comparison with the literature, and also showed higher antioxidant and antibacterial activities. Thus, these present green CuO and Cu2O nanoparticles deserve further attention to improve numerous medical applications.

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In recent years, a range of studies have been conducted with the aim to design and characterize delivery systems that are able to release multiple therapeutic agents in controlled and programmed temporal sequences, or with spatial resolution inside the body. This sequential release occurs in response to different stimuli, including changes in pH, redox potential, enzyme activity, temperature gradients, light irradiation, and by applying external magnetic and electrical fields. Sequential release (SR)-based delivery systems, are often based on a range of different micro- or nanocarriers and may offer a silver bullet in the battle against various diseases, such as cancer. Their distinctive characteristic is the ability to release one or more drugs (or release drugs along with genes) in a controlled sequence at different times or at different sites. This approach can lengthen gene expression periods, reduce the side effects of drugs, enhance the efficacy of drugs, and induce an anti-proliferative effect on cancer cells due to the synergistic effects of genes and drugs. The key objective of this review is to summarize recent progress in SR-based drug/gene delivery systems for cancer and other diseases.

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Carbosilane dendrimers are a particular type of dendrimer structure that has been used as delivery vehicles for drugs and nucleic acids. They have a defined structure according to their generation number, and their terminal groups can be rendered cationic or anionic. The cationic charges can address the limitation of electrostatic repulsion between the negatively charged phosphate groups of nucleic acids and negatively charged cell membranes. Specific drugs can be loaded into the central part of the dendrimer or attached at the exterior, and the overall positive charge may improve the efficacy of anti-inflammatory drugs. One promising feature of dendrimers is their non-toxicity both in vitro and in vivo up to therapeutic concentrations. Carbosilane dendrimers display good biocompatibility and can be used for anti-HIV, anti-viral, and anti-inflammatory applications, as well as for delivery of nucleic acids for anti-cancer therapy.

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused the COVID-19 pandemic that has been spreading around the world since December 2019. More than 10 million affected cases and more than half a million deaths have been reported so far, while no vaccine is yet available as a treatment. Considering the global healthcare urgency, several techniques, including whole genome sequencing and computed tomography imaging have been employed for diagnosing infected people. Considerable efforts are also directed at detecting and preventing different modes of community transmission. Among them is the rapid detection of virus presence on different surfaces with which people may come in contact. Detection based on non-contact optical techniques is very helpful in managing the spread of the virus, and to aid in the disinfection of surfaces. Nanomaterial-based methods are proven suitable for rapid detection. Given the immense need for science led innovative solutions, this manuscript critically reviews recent literature to specifically illustrate nano-engineered effective and rapid solutions. In addition, all the different techniques are critically analyzed, compared, and contrasted to identify the most promising methods. Moreover, promising research ideas for high accuracy of detection in trace concentrations, via color change and light-sensitive nanostructures, to assist fingerprint techniques (to identify the virus at the contact surface of the gas and solid phase) are also presented.

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Celiac disease is an autoimmune disorder, represented by the ingestion of the gluten protein usually found in wheat, barley and rye. To date, ELISA is the most accurate method for determining the presence of anti-gliadin, which is cumbersome, expensive (compared to a suspension microarray technique), and requires extensive sample preparation. In this study, in order to establish a more accurate assay to identify gliadin at lower concentrations, optical nano biosensors using an indirect immunoassay method for gliadin detection was designed and fabricated. For this, polycaprolactone (PCL) nano- to micro-beads were fabricated as a platform for the gliadin antigen which were optimized and nano functionalized with amine groups for such purposes. The gliadin antibody, which is selective to gliadin, was then added to the beads. Static light scattering tests were conducted to determine PCL particle size distribution and sizes were found from 0.1 to 30 µm, which is suitable for flow cytometry detection devices. Anti-gliadin detection was performed using an anti IgG mouse antibody conjugated with FITC in a flowcytometry device to detect the smallest particle. Fluorescence intensity was investigated at different concentrations of anti-gliadin and a standard curve used to determine gluten concentration based on fluorescence intensity. Results showed that the fluorescence intensity increased with greater concentrations of anti-gliadin providing a very effective method of detection due to selectivity at a 5 ppm detection limit. This represents a new highly sensitive and fast method for anti-gliadin detection. Further, the disuse of a cross linker and the use of a dedicated antibody at a very low level (1μl) made this new method very economical to identify anti-gliadin concentrations at the nm level. In summary, this study provides a new, more accurate and sensitive, as well as less expensive system to detect anti-gliadin for the improved diagnosis of celiac disease.

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Since the emergence of mechanical bonds, considerable research efforts have been devoted to the construction of mechanically interlocked molecules (MIMs), including rotaxanes, catenanes, and molecular knots, due to their mechanically bonded components that can undergo molecular motions and create distinguishing features. They have demonstrated valuable functions in many areas of science such as polymer and materials science, nanotechnology and medicine. Furthermore, since MIMs are magnificently suited for constructing artificial molecular machines (AMMs), immense attention has currently been attracted to this area. Recent elaborate synthetic strategies accompanied by novel analytical characterization techniques have led to a number of elegant catenanes and rotaxanes for various applications. The challenge now is to make more and more sophisticated compounds and novel architectures in higher yields. Here, we provide a “state-of-the-art” overview of research involving advances in MIMs synthesis, the newest architectures and their applications since the announcement of the 2016 Nobel Prize in Chemistry and the increasing interest in research into this field. The present review is designed to cover most of the recent studies in the synthesis of catenanes and rotaxanes depicting novel synthetic procedures to generate unprecedented MIMs with diverse properties that have not been mentioned en bloc in any reviews before.

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Cationic polymers such as poly-l-lysine (PLL) are able to interact electrostatically with DNA to produce polymeric systems with nanometric diameters due to the neutralization and accumulation of DNA. This study integrates the outstanding properties of carbon quantum dots (CQDs) with PLL to develop a novel gene delivery vehicle with a core-shell hybrid nanostructure. The CQD/PLL core-shell nanoparticles (NPs) were, therefore, synthesized in such a way that they had narrow size distribution and an average diameter under 10 nm, both of which were confirmed by dynamic light scattering (DLS) and transmission electron microscopy (TEM). Fourier transform infrared (FTIR) spectroscopy exhibited that the PLL passivation agents were formed on the CQDs through releasing amine groups on their surface. The positive charge of the CQD/PLL core-shell NPs reduced from +15 to nearly zero mV after being loaded with DNA at the weight ratio of 2:1. These traceable, water-soluble, biocompatible, and tunable photoluminescent NPs demonstrated a quantum yield of around 12% and a cellular uptake of nearly 70%. The NPs also showed no considerable toxicity to the human embryonic kidney (HEK)-293T cells. Hence, these novel CQD/PLL core-shell NPs hold great promise as a non-toxic and efficient gene delivery vector.

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AgNPs@Chitosan and Co3O4-NPs@Chitosan were fabricated with Salvia hispanica. Results showed MZI values of 5 and 30 mm for Co3O4-NPs- and AgNPs@Chitosan against S.aureus, and 15 and 21 mm for Co3O4-NPs- and AgNPs@Chitosan against E.coli (24 hours, 20 μg/mL), respectively. MTT assays showed up to (80%, 90%), (71%, 75%) and (91%, 94%) mammalian cell viability for the green synthesized, chemically synthesized AgNPs and green synthesized AgNPs@Chitosan for HEK-293 and PC12 cells, respectively, and (70%, 71%), (59%, 62%) and (88%, 73%) for the related Co3O4-NPs (24 hours, 20 μg/mL). The photocatalytic activities showed dye degradation after 135 and 105 minutes for AgNPs@Chitosan and Co3O4-NPs@Chitosan, respectively. FESEM results showed differences in particle sizes (32 ± 3.0 nm for the AgNPs and 41 ± 3.0 nm for the Co3O4NPs) but AFM results showed lower roughness of the AgNPs@Chitosan (7.639 ± 0.85 nm) compared to Co3O4NPs@Chitosan (9.218 ± 0.93 nm), which resulted in potential biomedical applications.

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The current study aimed to determine the protective effect of AY9944 related to Caveolin-1 and Claudin-5 role in lipid raft, which can rescue the blood–brain barrier from enhanced permeability. Therefore, in vivo analyses were performed following ischemia in normal, ischemic, and AY9944-treated animal groups. The results revealed that AY9944 reduced the infarct size, edema, and brain water content. The extravasation of Alb-Alexa 594 and biocytin-TMR was minimum in the AY9944-treated animals. The results showed a significant decrease in the expression level of Caveolin-1 over 8 h and 48 h and a remarkable increase in the level of Claudin-5 over 48 h following ischemia in AY9944-treated animals. Molecular docking simulation demonstrated that AY9944 exerts a possible protective role via attenuating the interaction of the Caveolin-1 and cholesterol in lipid raft. These findings point out that AY9944 plays a protective role in stroke by means of blood–brain barrier preservation.

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Decorating photocatalysts with noble metal nanoparticles (e.g., Pt) often increases the catalysts’ photocatalytic activity and biomedical properties. Here, a simple and inexpensive method has been developed to prepare a Pt-Ag3PO4/CdS/chitosan composite, which was characterized and used for the visible light-induced photocatalytic and antibacterial studies. This synthesized composite showed superior photocatalytic activity for methylene blue degradation as a hazardous pollutant (the maximum dye degradation was observed in 90 min of treatment) and killing of Gram positive bacterial (Staphylococcus aureus and Bacillus cereus) as well as Gram negative bacteria (Klebsiella pneumoniae, Salmonella typhimurium, Escherichia coli, and Pseudomonas aeruginosa) under visible light irradiation. The antibacterial activity of CdS, CdS/Ag3PO4, and Pt-Ag3PO4/CdS/chitosan against E. coli, Pseudomonas aeruginosa, Salmonella typhimurium, Klebsiella pneumoniae, Staphylococcus aureus, and Bacillus cereus showed the zone of inhibition (mm) under visible light and under dark conditions at a concentration of 20 µg mL−1. Furthermore, the cell viability of the CdS/chitosan, Ag3PO4, Ag3PO4/CdS/chitosan, and Pt-Ag3PO4/CdS/chitosan were investigated on the human embryonic kidney 293 cells (HEK-293), Henrietta Lacks (HeLa), human liver cancer cell line (HepG2), and pheochromocytoma (PC12) cell lines. In addition, the results indicated that the photodegradation rate for Pt-Ag3PO4/CdS/chitosan is 3.53 times higher than that of CdS and 1.73 times higher than that of the CdS/Ag3PO4 composite. Moreover, Pt-Ag3PO4/CdS/chitosan with an optimal amount of CdS killed large areas of different bacteria and different cells separately in a shorter time period under visible-light irradiation, which shows significantly higher efficiency than pure CdS and other CdS/Ag3PO4 composites. The superb performances of this composite are attributed to its privileged properties, such as retarded recombination of photoinduced electron/hole pairs and a large specific surface area, making Pt-Ag3PO4/CdS/chitosan a valuable composite that can be deployed for a range of important applications, such as visible light-induced photocatalysis and antibacterial activity.

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Currently, Alzheimer's disease (AD) accounts for more than half of all dementia cases. Although genetics, age, and environmental factors affect the disease, the cause of AD is not yet fully known. Various drugs have been proposed for the prevention and treatment of AD, but the delivery of these therapeutic agents to the brain is difficult. The blood–brain barrier prevents systemic drugs from accessing the central nervous system and designing a suitable system to overcome this barrier has attracted much attention. The intranasal pathway, given its proximity to the brain, provides a great opportunity for drug delivery. Understanding the physiological characteristics of the nose can be useful in selecting the appropriate carrier and material. Some of the emerging vehicles used for nose‐to‐brain delivery of anti‐AD drugs are natural (such as chitosan) and polymeric (such as poly(lactic‐co‐glycolic acid) and polyethylene glycol) nanoparticles (NPs). This review discusses the hypotheses for AD pathogenesis and highlights recent advances in the applications of natural and polymeric NPs for treatment. The fundamental and applied aspects of this approach for nasal drug delivery to the brain are reviewed here with thoughts on what is needed for the field to mature also provided.

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The therapeutic effects of carotenoids as dietary supplements to control or even treat some specific diseases including diabetic retinopathy, cardiovascular diseases, bacterial infections, as well as breast, prostate, and skin cancer are discussed in this review and also thoughts on future research for their widespread use are emphasized. From the stability standpoint, carotenoids have low bioavailability and bioaccessibility owing to their poor water solubility, deterioration in the presence of environmental stresses such as oxygen, light, and high heat as well as rapid degradation during digestion. Nanoencapsulation technologies as wall or encapsulation materials have been increasingly used for improving food product functionality. Nanoencapsulation is a versatile process employed for the protection, entrapment, and the delivery of food bioactive products including carotenoids from diverse environmental conditions for extended shelf lives and for providing controlled release. Therefore, we present here, recent (mostly during the last five years) nanoencapsulation methods of carotenoids with various nanocarriers. To us, this review can be considered as the first highlighting not only the potential therapeutic effects of carotenoids on various diseases but also their most effective nanodelivery systems.

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Trisomy 21 is the most prevalent aneuploidy disorder among live-born children worldwide. It results from the presence of an extra copy of chromosome 21 which leads to a wide spectrum of pathophysiological abnormalities and intellectual disabilities. Nevertheless human chromosome 21 (HSA21) possess protein non-coding regions where HAS-21 derived-microRNA genes are transcribed from. In turn, these HSA21-derived miRNAs curb protein translation of several genes which are essential to meet memory and cognitive abilities. From the genetics and molecular biology standpoints, dissecting the mechanistic relationship between DS pathology/symptoms and five chromosome 21-encoded miRNAs including miR-99a, let-7c, miR-125b-2, miR-155 and miR-802 seems pivotal for unraveling novel therapeutic targets. Recently, several studies have successfully carried out small molecule inhibition of miRNAs function, maturation, and biogenesis. One might assume in the case of DS trisomy, the pharmacological inhibition of these five overexpressed miRNAs might open new avenues for amelioration of the DS symptoms and complications. In this review, we primarily elucidated the role of HSA21-encoded miRNAs in the DS pathology which in turn introduced and addressed important therapeutic targets. Moreover, we reviewed relevant pharmaceutical efforts that based their goals on inhibition of these pathological miRNAs at their different biogenesis steps. We have also discussed the challenges that undermine and question the reliability of miRNAs as none-invasive biomarkers in prenatal diagnosis.

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Zn-rich (GaN)1-x(ZnO)x nanostructure was synthesized in assistance of high-gravity technique in order to reduce the time of reaction and the temperature. The synthesized inorganic nanomaterial has been applied in both drug/gene delivery system, and as the first fully-inorganic nanomaterial, was investigated in a comprehensive cellular investigation as well. In order to increase the potential bioavailability, as well as the interactions with the pCRISPR, the nanomaterial was enriched with additional Zn ions. The nanomaterial and final nanocarrier was characterized in each step before and after any biological analysis via FESEM, AFM, TEM, FTIR and XRD. The polymer coated nanosystems were fully characterized, and the sustained DOX delivery of them were investigated as well as the comprehensive cytotoxicity investigations on the HEK-293, PC12, HepG2 and HeLa cell lines after 24, 48 and 72 hours of treatment, which showed that the nanomaterial had the acceptable and very good cell viability at minimum concentration (0.1 µg/mL) maximum concentration (10 µg/mL). Also, after coating with chitosan and alginate, the relative cell viability on the all of the cell lines increased in the range of 2.7% to 18.9%. In the next step, the nanosystems were tagged with pCRISPR to analyze the potential application in the co-delivery of drug/gene. The confocal laser scanning microscope (CLSM) images of the 4′,6-diamidino-2-phenylindole (DAPI) stained and DOX were showed that the Zn-rich (GaN)1-x(ZnO)x nanosystem has lower cellular density compared to the chitosan and alginate coated nanosystems; however, all of them showed acceptable and suitable localization of DOX into the nanostructure and the cells and effective drug delivery procedure along with sustained behaviors in different pH’s. Furthermore, the CLSM images of the HEK-293 and HeLa cell lines showed successful delivery of pCRISPR into the cells, and the enhanced green fluorescent protein (EGFP) reached up to 9.3% for the HeLa cell line, which is a record by itself. In addition, the exact morphology of the nanosystems before and after drug/gene delivery procedures were investigated via FESEM and TEM, and showed that in the presence of polymer coating, the morphology of the substrates was intact.

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The novel coronavirus pandemic has rapidly spread around the world since December 2019. Various techniques have been applied in identification of SARS-CoV-2 or COVID-19 infection including computed tomography imaging, whole genome sequencing, and molecular methods such as reverse transcription polymerase chain reaction (RT-PCR). This review article discusses the diagnostic methods currently being deployed for SARS-CoV-2 identification including optical biosensors and point-of-care diagnostics that are on the horizon. These innovative technologies may provide a more accurate, sensitive and rapid diagnosis of SARS-CoV-2 to manage the present novel coronavirus outbreak, and could be beneficial in preventing any future epidemics. Furthermore, the use of green synthesized nanomaterials in the optical biosensor devices could leads to sustainable and environmentally-friendly approaches for this crisis.

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Herein, in a one-pot method, the reduced graphene oxide layers with the assistance of multiwalled carbon nanotubes were decorated to provide a suitable space for the in situ growth of CoNi2S4, and the porphyrins were incorporated into the layers as well to increase the sensitivity of the prepared nanostructure. The prepared nanocomposite can establish π–π interactions between the genetic material and on the surface of porphyrin rings. Also, hydrogen bonds between genetic domains and the porphyrin’ nitrogen and the surface hydroxyl groups are probable. Furthermore, the potential donor–acceptor relationship between the d7 transition metal, cobalt, and the genetic material provides a suitable way to increase the interaction and gene loading , and transfections. The reason for this phenomenon was optimized to increase the EGFP by up to 17.9%. Furthermore, the sensing ability of the nanocomposite towards H2O2 was investigated. In this regard, the limit of detection of the H2O2 obtained 10 µM. Also, the in situ biosensing ability in the HEK-293 and PC12 cell lines was evaluated by the addition of PMA. The nanocomposite showed the ability to detect the released H2O2 after adding the minimum amount of 120 ng/mL of the PMA.

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The main aim of the present study was to fabricate levofloxacin (LEV)-loaded halloysite nanotube (HNT)/sodium alginate (SA)-poly (ethylene oxide) (PEO) nanocomposite fibrous mats and evaluate their drug release and antibacterial activity. LEV was incorporated into the lumen of HA nanotubes via cyclic vacuum pumping in/out process. Structure and morphology of HNT-LEV nanohybrid particles and HNT-LEV/SA-PEO nanocomposite fibers were characterized via X-ray diffractometer (XRD), scanning electron microscope (SEM), transmission electron microscope (TEM), thermogravimetric analysis (TGA), and fourier transform infrared (FT-IR) techniques. SEM images indicated that the addition of HNT-LEV nanohybrid particles and LEV into the fabricated nanofibers resulted in changing their average diameter. In-vitro release profile showed that LEV release from HNT-LEV/SA-PEO nanocomposite fibers slowly occurred. Their anti-bacterial activity was studied against S. aureus and E. coli and found that HNT-LEV/SA-PEO nanocomposite fibers show suitable antimicrobial activity. Sustained drug release profile and suitable anti-bacterial activity of HNT-LEV/SA-PEO nanocomposite fibers indicated that it was a good biomaterial for wound dressings.

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Hybrid bioactive inorganic–organic carbon-based nanocomposites of reduced graphene oxide (rGO) nanosheets enlarged with multi-walled carbon nanotubes (MWCNTs) were decorated to provide a suitable space for in situ growth of CoNi2S4 and green-synthesized ZnO nanoparticles. The ensuing nanocarrier supplied π–π interactions between the DOX drug and a stabilizing agent derived from leaf extracts on the surface of ZnO nanoparticles and hydrogen bonds; gene delivery of (p)CRISPR was also facilitated by chitosan and alginate renewable macromolecules. Also, these polymers can inhibit the potential interactions between the inorganic parts and cellular membranes to reduce the potential cytotoxicity. Nanocomposite/nanocarrier analyses and sustained DOX delivery (cytotoxicity analyses on HEK-293, PC12, HepG2, and HeLa cell lines after 24, 48, and 72 h) were indicative of an acceptable cell viability of up to 91.4 and 78.8% after 48 at low and high concentrations of 0.1 and 10 μg/mL, respectively. The MTT results indicate that by addition of DOX to the nanostructures, the relative cell viability increased after 72 h of treatment; since the inorganic compartments, specifically CoNi2S4, are toxic, this is a promising route to increase the bioavailability of the nanocarrier before reaching the targeted cells. Nanosystems were tagged with (p)CRISPR for co-transfer of the drug/genes, where confocal laser scanning microscopy (CLSM) pictures of the 4′,6-diamidino-2-phenylindole (DAPI) were indicative of appropriate localization of DOX into the nanostructure with effective cell and drug delivery at varied pH. Also, the intrinsic toxicity of CoNi2S4 does not affect the morphology of the cells, which is a breakthrough. Furthermore, the CLSM images of the HEK-293 and HeLa cell displayed effective transport of (p)CRISPR into the cells with an enhanced green fluorescent protein (EGFP) of up to 8.3% for the HEK-293 cell line and 21.4% for the HeLa cell line, a record. Additionally, the specific morphology of the nanosystems before and after the drug/gene transport events, via images by TEM and FESEM, revealed an intact morphology for these biopolymers and their complete degradation after long-time usage.

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Safe and efficient delivery of CRISPR/Cas9 systems is still a challenge. Here we report the development of fluorescent nitrogen- and zinc-doped carbon dots (N–Zn-doped CDs) using one-step microwave-aided pyrolysis based on citric acid, branched PEI25k, and different zinc salts. These versatile nanovectors with a quantum yield of around 60% could not only transfect large CRISPR plasmids (∼9 kb) with higher efficiency (80%) compared to PEI25k and lipofectamine 2000 (Lipo 2K), but they also delivered mRNA into HEK 293T cells with the efficiency 20 times greater than and equal to that of PEI25k and Lipo 2K, respectively. Unlike PEI25k, N–Zn-doped CDs exhibited good transfection efficiency even at low plasmid doses and in the presence of 10% fetal bovine serum (FBS). Moreover, these nanovectors demonstrated excellent efficiency in GFP gene disruption by transferring plasmid encoding Cas9 and sgRNA targeting GFP as well as Cas9/sgRNA ribonucleoproteins into HEK 293T-GFP cells. Hence, N–Zn-doped CDs with remarkable photoluminescence properties and high transfection efficiency in the delivery of both CRISPR complexes and mRNA provide a promising platform for developing safe, efficient, and traceable delivery systems for biological research.

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Aim: To develop a novel nanovector for the delivery of genetic fragments and CRISPR/Cas9 systems in particular. Materials & methods: Vitamin D3-functionalized carbon dots (D/CDs) fabricated using one-step microwave-aided methods were characterized by different microscopic and spectroscopic techniques. The 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl tetrazolium bromide assay and flow cytometry were employed to determine the cell viability and transfection efficiency. Results: D/CDs transfected CRISPR plasmid in various cell lines with high efficiency while maintaining their remarkable efficacy at high serum concentration and low plasmid doses. They also showed great potential for the green fluorescent protein disruption by delivering two different types of CRISPR/Cas9 systems. Conclusion: Given their high efficiency and safety, D/CDs provide a versatile gene-delivery vector for clinical applications.

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There have been numerous advancements in the early diagnosis, detection, and treatment of genetic diseases. In this regard, CRISPR technology is promising to treat some types of genetic issues. In this study, the relationship between calcium (due to its considerable physicochemical properties) and chitosan (as a natural linear polysaccharide) was investigated and optimized for pCRISPR delivery. To achieve this, different forms of calcium, such as calcium nanoparticles (CaNPs), calcium phosphate (CaP), a binary blend of calcium and chitosan including CaNPs/Chitosan and CaP/Chitosan, as well as their tertiary blend including CaNPs–CaP/Chitosan, were prepared via both routine and green procedures using Salvia hispanica to reduce toxicity and increase nanoparticle stability (with a yield of 85%). Such materials were also applied to the human embryonic kidney (HEK-293) cell line for pCRISPR delivery. The results were optimized using different characterization techniques demonstrating acceptable binding with DNA (for both CaNPs/Chitosan and CaNPs–CaP/Chitosan) significantly enhancing green fluorescent protein (EGFP) (about 25% for CaP/Chitosan and more than 14% for CaNPs–CaP/Chitosan).

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Carbon dots (CDs) have become the focus of many studies due to their outstanding optical properties and good biocompatibility. We investigated their potential application to produce a smart and highly efficient yet nontoxic nanovector for gene delivery. This was achieved by conjugating PEI1.8k-functionalized CDs (synthesized by one-step microwave-assisted pyrolysis) with arginine-disulfide linkers to produce CD-PEI1.8k-Arg nanoparticles. This nanovector could deliver p-CRISPR (9.3 kb) into different types of cell lines with higher efficiency compared to native PEI1.8k or PEI25k. CD-PEI1.8k-Arg also maintained its outstanding transfection efficiency at a high serum concentration and low p-CRISPR dose, compared to PEI25k, which was ineffective under those conditions. Additionally, CD-PEI1.8k-Arg could knock out the GFP gene with great efficiency by delivering the required components of CRISPR/Cas9, including a plasmid encoding Cas9, sgRNA targeting GFP, and Cas9/sgRNA ribonucleoproteins (RNPs) into the HEK 293T-GFP cells. Moreover, the nanoparticles showed potential for the local delivery of p-CRISPR into brain tissue. The remarkable properties of CD-PEI1.8k-Arg could enable the development of a safe, highly efficient gene-delivery nanovector for the treatment of various diseases in the near future.

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The aim of this work was to provide a novel approach to designing and synthesizing a nanocomposite with significant biocompatibility, biodegradability, and stability in biological microenvironments. Hence, the porous ultra-low-density materials, metal–organic frameworks (MOFs), have been considered and the MIL-125(Ti) has been chosen due to its distinctive characteristics such as great biocompatibility and good biodegradability immobilized on the surface of the reduced graphene oxide (rGO). Based on the results, the presence of transition metal complexes next to the drug not only can reinforce the stability of the drug on the structure by preparing π–π interaction between ligands and the drug but also can enhance the efficiency of the drug by preventing the spontaneous release. The effect of utilizing transition metal complex beside drug (Doxorubicin (DOX)) on the drug loading, drug release, and antibacterial activity of prepared nanocomposites on the P. aeruginosa and S. aureus as a model bacterium has been investigated and the results revealed that this theory leads to increasing about 200% in antibacterial activity. In addition, uptake, the release of the drug, and relative cell viabilities (in vitro and in vivo) of prepared nanomaterials and biomaterials have been discussed. Based on collected data, the median size of prepared nanocomposites was 156.2 nm, and their biological stability in PBS and DMEM + 10% FBS was screened and revealed that after 2.880 min, the nanocomposite’s size reached 242.3 and 516 nm respectively. The MTT results demonstrated that immobilizing PdL beside DOX leads to an increase of more than 15% in the cell viability. It is noticeable that the AST:ALT result of prepared nanocomposite was under 1.5.

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Nanotechnology is one of the most impressive sciences in the twenty-first century. Not surprisingly, nanoparticles/nanomaterials have been widely deployed given their multifunctional attributes and ease of preparation via environmentally friendly, cost-effective, and simple methods. Although there are assorted optimized preparative methods for synthesizing the nanoparticles, the main challenge is to find a comprehensive method that has multifaceted properties. The goal of this study has been to synthesize aminated (nano)particles via the Rosmarinus officinalis leaf extract-mediated copper oxide; this modification leads to the preparation of (nano)particles with promising biological and photocatalytic applications. The synthesized NPs have been fully characterized, and biological activity was evaluated in antibacterial assessment against Bacillus cereus as a model Gram-positive and Pseudomonas aeruginosa as a model Gram-negative bacterium. The bio-synthesized copper oxide (nano)particles were screened by MTT assay by applying the HEK-293 cell line. The aminated (nano)particles have shown lower cytotoxicity (~ 21%), higher (~ 50%) antibacterial activity, and a considerable increase in zeta potential value (~ + 13.4 mV). The prepared (nano)particles also revealed considerable photocatalytic activity compared to other studies wherein the dye degradation process attained 97.4% promising efficiency in only 80 min and just 7% degradation after 80 min under dark conditions. The biosynthesized copper oxide (CuO) (nano)particle’s biomedical investigation underscores an eco-friendly synthesis of (nano)particles, their noticeable stability in the green reaction media, and impressive biological activity.

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The main goal of the present project was to design and develop ibuprofen (IBU) and layered double hydroxides-vancomycin (LDH-VAN) nanohybrid loaded bionanocomposite fibrous mats to increase the wound healing rate. Thus, first, LDH-VAN nanohybrid particles was synthesized by in-situ incorporation of VAN into the Mg-Al-LDH interlayers during the co-precipitation of hydroxides. Then, LDH-VAN/IBU/CMC-PEO bionanocomposite fibrous mats were fabricated by electrospinning technique. Test samples were examined XRD, SEM, TEM, TGA, and FTIR. In vitro drug release test was performed in the phosphate buffer solution (pH = 7.4) to prove the efficiency of the fabricated bionanocomposite fibrous mats as a sustained-release carrier for both VAN and IBU. All the fabricated bionanocomposite fibrous mats did not displayed any significant cytotoxicity on NIH/3 T3 fibroblast cells. The wound area in the rats treated with LDH-VAN/IBU/CMC-PEO bionanocomposite fibrous mats was less than other treatment groups. Based on histological analysis, the LDH-VAN/IBU/CMC-PEO bionanocomposite fibrous mats possess a faster wound healing than other nanofibrous mats. Data obtained from the present project indicated that LDH-VAN/IBU/CMC-PEO bionanocomposite fibrous mats could accelerate the wound healing process.

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Hybrid inorganic/organic compounds opened up the window of opportunities to a wide variety of fields. The carbon-based nanocomposite (Fe3O4/MWCNT-COOH/Extract/PdL@DOX/p-CRISPR/Extract) have been prepared using tangerine and egg white extract as a second layer of nanocomposites. Then, doxorubicin (DOX) and PdC16H10N4O3 (PdL) were added to the mixture. Based on the previous studies, L (carboxamide-based ligand) has a potent desire for connecting and then blocking the HER-2, and σ2 (tumor's overexpressed receptors) and PdL could enhance the sustainability of the DOX by hydrogen bonding and π-π interaction. The effect of biotin on site-specific delivery has been investigated by utilizing two different types of extracts that naturally has a different amount of biotin. Based on this study's results, settling natural extracts (tangerine and egg white), bioactive complexes, and Fe3O4 on the functionalized-MWCNT can strengthen the nanocarrier's stability in the biological matrix, make more active porosity, and control the internalization to the cells for drug/gene delivery. The nanocarrier has revealed 29.1% ± 1.5% GFP positive transfection efficiency. Also, MTT assay (HEK-293, MCF-7 and PC-12) and antibacterial activity and in vivo testing (H&E and AST:ALT analysis) have been screened and showed promising results.

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A pH-sensitive bilayer electrospun nanofibrous mat containing both antibiotic (gentamicin sulfate, GEN) and non-steroidal anti-inflammatory (diclofenac sodium, DIC) drugs was fabricated for burn wound dressing by electrospinning technique, in which ethyl cellulose (EC) and ethyl cellulose/Eudragit S-100 (EC/ES-100) formed the top and bottom layers, respectively. The fabricated pH-sensitive bilayer electrospun nanofibrous mats were characterized from aspects of both structure and efficiency. Physicochemical properties were investigated via SEM, FTIR, and TGA. The swelling ratio and in vitro drug release of the fabricated nanofibrous mats were studied in different pHs. MTT was applied to assess the safety of the fiber mats. Finally, the in vivo efficiency of the designed pH-sensitive bilayer electrospun nanofibrous mats was examined on the male Wistar rats. Based on the histological analysis and wound healing test (in vivo animal experiments), the (ES100/EC-DIC/GEN)-(EC) pH-sensitive bilayer nanofibrous mat displayed faster wound healing than other bilayer nanofibrous mat. As a result, (ES100/EC-DIC/GEN)-(EC) bilayer nanofibrous mat with pH-responsion could accelerate the burn wound healing process via decreasing the adverse effects of GEN and DIC as topical antimicrobial and anti-inflammatory agents, receptively.

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Personalized medicine is a new approach toward safer and even cheaper treatments with minimal side effects and toxicity. Planning a therapy based on individual properties causes an effective result in a patient’s treatment, especially in a complex disease such as cancer. The benefits of personalized medicine include not only early diagnosis with high accuracy but also a more appropriate and effective therapeutic approach based on the unique clinical, genetic, and epigenetic features and biomarker profiles of a specific patient’s disease. In order to achieve personalized cancer therapy, understanding cancer biology plays an important role. One of the crucial applications of personalized medicine that has gained consideration more recently due to its capability in developing disease therapy is related to the field of stem cells. We review various applications of pluripotent, somatic, and cancer stem cells in personalized medicine, including targeted cancer therapy, cancer modeling, diagnostics, and drug screening. CRISPR-Cas gene-editing technology is then discussed as a state-of-the-art biotechnological advance with substantial impacts on medical and therapeutic applications. As part of this section, the role of CRISPR-Cas genome editing in recent cancer studies is reviewed as a further example of personalized medicine application.

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